Substituted amphetamine
Encyclopedia
Substituted amphetamines are a chemical class of stimulants, entactogens
, hallucinogens, and other drug
s. They feature a phenethylamine
core with a methyl group
attached to the alpha carbon resulting in amphetamine
, along with additional substitution
s. Examples of amphetamines are amphetamine
(itself), methamphetamine
, ephedrine
, cathinone
, MDMA ("Ecstasy"), and DOM
("STP").
Amphetamine derivatives occur in nature, for example in the leaves of Ephedra
and khat
plants. These have been used since antiquity for their pharmacological effects. Amphetamines were first produced synthetically at the end of the 19th century. By the 1930s such synthetic amphetamines found use as decongestants in the symptomatic treatment of cold
s and also occasionally as psychoactive agents. Their effects on the central nervous system
are diverse, but can be summarized by three overlapping types of activity: psychoanaleptic
, hallucinogenic
and empathogenic
. Various amphetamines may cause these actions either separately or in combination. Improper consumption of amphetamine derivatives may result in addiction
and aggressiveness, as well as in rapid deterioration of basic body functions and death. Therefore, production and distribution of most related drugs are controlled by the authorities both nationally and internationally.
, was synthesized earlier, Ephedra
was used 5000 years ago in China as a medicinal plant
; its active ingredients are alkaloids ephedrine, pseudoephedrine
, norephedrine (phenylpropanolamine
) and norpseudoephedrine (cathine
). Natives of Yemen
and Ethiopia
have a long tradition of chewing khat
leaves to achieve a stimulating effect. The active substances of khat are cathinone and to a lesser extent cathine.
Amphetamine was first synthesized in 1887 by Romania
n chemist Lazăr Edeleanu
and did not attract special attention. MDMA was produced in 1912 (according to other sources in 1914) as an intermediate product. However, this synthesis also went largely unnoticed. In the 1920s, both methamphetamine and an optical isomer of amphetamine dextroamphetamine
(D-amphetamines) were synthesized. This synthesis was a by-product of a search for ephedrine, a bronchodialator used to treat asthma
extracted exclusively from natural sources. Over-the-counter use of amphetamines was initiated in early 1930s by the pharmaceutical company Smith, Kline & French (now part of GlaxoSmithKline
), as a medicine (Benzedrine
) for cold
s and nasal congestion
. Subsequently, amphetamine was used in the treatment of narcolepsy
, obesity
, hay fever
, orthostatic hypotension
, epilepsy
, Parkinson's disease
, alcoholism
and migraine
. The "reinforcing" effects of amphetamines were quickly discovered, and the misuse of amphetamines had been noted as far back as 1936.
During World War II
, amphetamines were used by the German military to keep their tank crews awake for long periods, and treat depression
. It was noticed that extended rest was required after such artificially induced activity.
The widespread use of amphetamines began in the postwar Japan
and quickly spread to other countries. Modified ("designer"), amphetamines gained popularity since 1960s, such as MDA
and PMA. MDMA was rediscovered and popularized by the American chemist Alexander Shulgin
in 1965, after which it was used for some time in psychotherapy
sessions. In 1970, the United States
adopted "the Controlled Substances Act" that limited non-medical use of amphetamines. Street use of PMA was noted in 1972, and in 1985, MDMA was banned by the US authorities in an emergency scheduling initiated by the US Drug Enforcement Agency.
Since the mid 1990s, MDMA ("ecstasy") became a popular entactogenic drug among the youth and quite often non-MDMA substances were sold as "ecstasy". In the first legally sanctioned trials in the USA in over twenty years, the safety profile of MDMA has been demonstrated, and it has been shown to be a successful adjunct to psychotherapy in the management of treatment-resistant Post-Traumatic Stress Disorder (PTSD) in victims of sexual abuse and sufferers of other conditions.
class of compounds. Substitution of hydrogen atoms results in a large class of compounds. Typical reaction is substitution by methyl and sometimes ethyl group
s at the amine
and phenyl
sites:
are diverse and can be attributed to the three main classes:
Studies on animals have shown that these classes of effects are independent. Various amphetamines may cause these actions, either separately or in combination; for example, amphetamine adds hallucination
effect at high doses (amphetamine psychosis), however this is quite different than the 'hallucinongenic' phenomena that are typically associated with what are often commonly referred to as the psychedelic amphetamines. The stimulating effect of amphetamine is similar to that of cocaine
, but lasts longer.
and dopamine
. In the normal operation, synaptic release of catecholamines is carried out by exocytosis
of a vesicle which contain a neurotransmitter
. Then, the neurotransmitter is reabsorbed
from the synaptic cleft into the cytoplasm of the neuron. From the cytoplasm, the neurotransmitter penetrates back into the vesicles via the action of the vesicular monoamine transporter
(VMAT).
Presence of amphetamine and its derivative inverts the direction of the transport: neurotransmitter moves from vesicles to the cytoplasm and then to the synaptic cleft. As a result, vesicles are emptied, vesicular release of neurotransmitter is reduced, and the concentration of neurotransmitter in the synaptic cleft increases. In this three mechanisms are utilized:
Inhibitors of reuptake of monoamines, such as cocaine
, reduce the emission of monoamines, caused by amphetamine-type stimulants. Effects of hallucinogenic amphetamines is similar to other classical hallucinogens and is related to their agonism
to serotonin
receptor of the type 5-HT2A
. Also, lesser-known mechanisms possibly associated with hallucinogenic effects (in traditional plain stimulant and non-hallucinogen class amphetamines) may potentially include agonism of the trace amine-associated receptor
s (TAARs) and other functions of the amphetamine molecular skeleton in the CNS.
Replacing methyl group
in the position α to ethyl group reduces the stimulating and hallucinogenic actions, but does not affect the empathogenic action (as in MBDB
) and suppression of appetite (as in phentermine
). Removing the methyl group in position α usually decreases the effectiveness of substance; thus, phenethylamine
poorly penetrates the blood-brain barrier
and is rapidly metabolized. Substitutions in the phenyl group
decrease the stimulating action, but may induce other effects. Substitution in position 4 is usually associated with serotonergic action.
Right-handed (dextrorotatory) enantiomers of amphetamines, such as dextroamphetamine, are usually 4–10 times more potent than left-handed, with the exception for MDMA and a few related substances whose efficiency does not depend on the isomerism.
is mainly due to emissions of norepinephrine
. This enhances stimulation of α-and β-adrenoreceptors
that can lead to tachycardia
(increased heart rate), elevated blood pressure
, mydriasis
(dilated pupils), sweat
ing and hyperthermia
(elevated body temperature).
s. Regarding central nervous system
, it can manifest itself as psychosis, visual and tactile
hallucination
and anxiety. The effects on cardiovascular system are expressed as tachycardia and increased blood pressure. The immediate causes of death from the use of amphetamines are usually hyperthermia, heart arrhythmia or stroke
.
Unlike many other drugs, amphetamine and especially methamphetamine are neurotoxic and can irreversibly damage dopaminergic
and serotonergic
neuron
s. It is believed that the toxic effect of amphetamines on dopaminergic neurons is associated with the formation of free radicals
and peroxynitrite
, which is a strong oxidizer. MDMA, moreover, reduces concentration of antioxidant
s glutathione
and vitamin E
in the brain, and is therefore neurotoxic in high doses. Whether or not MDMA is neurotoxic as a result of prolonged use in normal doses is being debated.
that can last up to several weeks. Some energy drinks contain small levels of amphetamines depending on size and quantity; which can be mistaken in few drug test, depending on time, and amount of consumption. It is believed that psychological dependence on amphetamines, as well as on other drugs, is associated with stimulation by the drug of dopaminergic neurons in the ventral tegmental area. Those neurons are responsible for feelings of reward that affect the processes of learning and adaptation.
Physical dependence on amphetamine-type stimulants is controversial. Interruption after their prolonged use results in fatigue, depression
, sleepiness and feeling of hunger
. These symptoms may be regarded as components of withdrawal syndrome
or just as normal response of the body to the lack of sleep and food that accompanies systematic use of amphetamine-type stimulants.
Classic hallucinogens (such as DOM
) do not cause addiction. Laboratory animals which were taught to use stimulants did not use hallucinogens on their own initiative.
s, phosphate
s and chloride
s). Amphetamine is usually sold as tablets and sometimes as capsules or syrup. Methamphetamine is usually available as a powder for inhalation or preparing a solution for intravenous injection, and less often as tablets or capsules. Also common is crystalline methamphetamine hydrochloride intended for smoking. Methylenedioxyamphetamines (MDMA, MDEA) are usually tablets.
Amphetamines have good bioavailability
upon oral or intranasal administration. Because of their lipophilicity, amphetamines easily penetrate the blood-brain barrier
. A typical oral dose is 5–20 mg for amphetamine and methamphetamine., 80–150 mg for MDA and MDMA, 3–10 mg for DOM
and 1–3 mg for DOB
. Biological half-life
is 8–30 h for amphetamine, 12–34 h for methamphetamine and 5–10 h for MDMA.
The action of amphetamines usually lasts 4–6 hours, but in some cases up to 24 hours.
by intravenous injection. Hyperthermia is reduced with external cooling and some measures might be taken to increase urination, in order to excrete the poison.
Treatment of addiction to amphetamine and its derivatives are similar to those for other stimulants such as cocaine. Because of the weak physical effect of amphetamine addiction, the use of amphetamines is interrupted abruptly instead of gradually reducing the drug dose.
The major symptoms of psychological addiction are depression, feeling of boredom and nostalgia for the pleasure associated with the drug. The treatment is usually based on individual work with the patient and the patient's desire to quit drug use. Despite ongoing intensive search, by 2008, efficient medical treatment has not been available. Although the tests are far from complete, some positive results were achieved with the following drugs:
compounds. Exceptions include cathinone which is present in khat leaves and ephedrine and pseudoephedrine
, the active components of Ephedra
. These natural alkaloids have a much weaker effect than the amphetamine.
reactions of ephedrine. Ephedrine itself can be extracted from Ephedra
.
Similarly, from norephedrine (phenylpropanolamine) can be obtained from amphetamine. Methcathinone
(the n-methyl homologue of cathinone) can be obtained by oxidation of ephedrine with potassium permanganate
in the presence of acetic acid
. Cathinone can be produced by a similar oxidation of phenylpropanolamine
(norephedrine).
– the main component of the Sassafras
oil – is used for the synthesis of MDA, MDMA and other amphetamines containing methylenedioxyphenyl group as follows:
amalgam
.
P2P itself is usually obtained from phenylacetic acid
and acetic anhydride
.
Similarly, MDA or MDMA can be produced from 3,4-methylenedioxyphenyl-2-propanone (MDP2P
), and the MDP2P can be obtained from piperonal
.
with nitroethane
using amine
as a catalyst, followed by reduction using, e.g. lithium aluminum hydride. Derivatives of benzaldehyde are used in reactions occurring via substitution of the phenyl group of benzaldehyde. For example, piperonal
is used for preparing MDA, and it can in turn be extracted as alkaloid piperine
present in black pepper
.
Currently, the application of amphetamines and their derivatives in medicine is very limited. Amphetamine, dextroamphetamine, methamphetamine and methylphenidate
(Ritalin) are used in the treatment of narcolepsy
and attention-deficit hyperactivity disorder
. Bupropion
, a substituted cathinone with very weak psychostimulant properties relative to most chemicals of this class, is widely used as an atypical antidepressant
and smoking cessation
aid, under the brand names Wellbutrin and Zyban, and is also used off-label to treat attention-deficit hyperactive disorder.
According to UN Office on Drugs and Crime
(UNODC), the world's illegal production in 2007 was 230 to 640 tons of amphetamine-type stimulants (amphetamine, methamphetamine, methcathinone and derivatives) and 72 to 137 tons of methylenedioxyamphetamine (MDA, MDMA, MDEA). The global market for amphetamine-type stimulants is estimated at $65 billion. Production of amphetamines is mainly concentrated near the markets. The trade is mainly concentrated within a country in order to avoid customs control. North America (mainly the states California
and Oregon
) is the leader in the production of methamphetamine, whereas Europe dominates the production of amphetamine and methylenedioxyamphetamine (MDA, MDMA, MDEA).
UNODC
estimates that between 15 and 50 million people used amphetamines at least once during the year of 2007, that constitutes 0.4–1.2% of the total population aged 15 to 64. In Russia, amphetamines are the third most popular type of drug after marijuana and opiate
s.
Empathogen-entactogen
The terms empathogen and entactogen are used to describe a class of psychoactive drugs that produce distinctive emotional and social effects similar to those of MDMA. Putative members of this class include 2C-B, 2C-I, MDMA, MDA, MDEA, MBDB, 2C-T-7, and 2C-T-2, among others...
, hallucinogens, and other drug
Drug
A drug, broadly speaking, is any substance that, when absorbed into the body of a living organism, alters normal bodily function. There is no single, precise definition, as there are different meanings in drug control law, government regulations, medicine, and colloquial usage.In pharmacology, a...
s. They feature a phenethylamine
Phenethylamine
Phenylethylamine or phenethylamine is a natural monoamine alkaloid, trace amine, and also the name of a class of chemicals with many members well known for psychoactive drug and stimulant effects. Studies suggest that phenylethylamine functions as a neuromodulator or neurotransmitter in the...
core with a methyl group
Functional group
In organic chemistry, functional groups are specific groups of atoms within molecules that are responsible for the characteristic chemical reactions of those molecules. The same functional group will undergo the same or similar chemical reaction regardless of the size of the molecule it is a part of...
attached to the alpha carbon resulting in amphetamine
Amphetamine
Amphetamine or amfetamine is a psychostimulant drug of the phenethylamine class which produces increased wakefulness and focus in association with decreased fatigue and appetite.Brand names of medications that contain, or metabolize into, amphetamine include Adderall, Dexedrine, Dextrostat,...
, along with additional substitution
Substitution reaction
In a substitution reaction, a functional group in a particular chemical compound is replaced by another group. In organic chemistry, the electrophilic and nucleophilic substitution reactions are of prime importance...
s. Examples of amphetamines are amphetamine
Amphetamine
Amphetamine or amfetamine is a psychostimulant drug of the phenethylamine class which produces increased wakefulness and focus in association with decreased fatigue and appetite.Brand names of medications that contain, or metabolize into, amphetamine include Adderall, Dexedrine, Dextrostat,...
(itself), methamphetamine
Methamphetamine
Methamphetamine is a psychostimulant of the phenethylamine and amphetamine class of psychoactive drugs...
, ephedrine
Ephedrine
Ephedrine is a sympathomimetic amine commonly used as a stimulant, appetite suppressant, concentration aid, decongestant, and to treat hypotension associated with anaesthesia....
, cathinone
Cathinone
Cathinone, or Benzoylethanamine, is a monoamine alkaloid found in the shrub Catha edulis and is chemically similar to ephedrine, cathine and other amphetamines. Cathinone induces the release of dopamine from striatal preparations that are prelabelled either with dopamine or its precursors. It is...
, MDMA ("Ecstasy"), and DOM
2,5-Dimethoxy-4-methylamphetamine
2,5-Dimethoxy-4-methylamphetamine is a psychedelic and a substituted amphetamine...
("STP").
Amphetamine derivatives occur in nature, for example in the leaves of Ephedra
Ephedra (genus)
Ephedra is a genus of gymnosperm shrubs, the only genus in its family, Ephedraceae, and order, Ephedrales. Ephedra grows in dry climates over wide areas of the northern hemisphere, including southwestern North America, Europe, north Africa, and southwest and central Asia, and, in the southern...
and khat
Khat
Khat, qat, gat or Waquish Spoken from true Yemeni, is a flowering plant native to tropical East Africa and the Arabian Peninsula....
plants. These have been used since antiquity for their pharmacological effects. Amphetamines were first produced synthetically at the end of the 19th century. By the 1930s such synthetic amphetamines found use as decongestants in the symptomatic treatment of cold
Cold
Cold describes the condition of low temperature.Cold may also refer to:*Common cold, a contagious viral infectious disease of the upper respiratory system*Chronic obstructive pulmonary disease...
s and also occasionally as psychoactive agents. Their effects on the central nervous system
Central nervous system
The central nervous system is the part of the nervous system that integrates the information that it receives from, and coordinates the activity of, all parts of the bodies of bilaterian animals—that is, all multicellular animals except sponges and radially symmetric animals such as jellyfish...
are diverse, but can be summarized by three overlapping types of activity: psychoanaleptic
Psychoanaleptic
In pharmacology, a psychoanaleptic is a medication that produces an arousing effect upon the patient.Antidepressants, psychostimulants, agents used for ADHD and nootropics, and Anti-dementia drugs are all psychoanaleptics....
, hallucinogenic
Psychedelics, dissociatives and deliriants
This general group of pharmacological agents can be divided into three broad categories: psychedelics, dissociatives, and deliriants. These classes of psychoactive drugs have in common that they can cause subjective changes in perception, thought, emotion and consciousness...
and empathogenic
Empathogen-entactogen
The terms empathogen and entactogen are used to describe a class of psychoactive drugs that produce distinctive emotional and social effects similar to those of MDMA. Putative members of this class include 2C-B, 2C-I, MDMA, MDA, MDEA, MBDB, 2C-T-7, and 2C-T-2, among others...
. Various amphetamines may cause these actions either separately or in combination. Improper consumption of amphetamine derivatives may result in addiction
Addiction
Historically, addiction has been defined as physical and psychological dependence on psychoactive substances which cross the blood-brain barrier once ingested, temporarily altering the chemical milieu of the brain.Addiction can also be viewed as a continued involvement with a substance or activity...
and aggressiveness, as well as in rapid deterioration of basic body functions and death. Therefore, production and distribution of most related drugs are controlled by the authorities both nationally and internationally.
History
Although the basic compound of the class, amphetamineAmphetamine
Amphetamine or amfetamine is a psychostimulant drug of the phenethylamine class which produces increased wakefulness and focus in association with decreased fatigue and appetite.Brand names of medications that contain, or metabolize into, amphetamine include Adderall, Dexedrine, Dextrostat,...
, was synthesized earlier, Ephedra
Ephedra
Ephedra refers to the plant Ephedra sinica. E. sinica, known in Chinese as ma huang , has been used in traditional Chinese medicine for 5,000 years for the treatment of asthma and hay fever, as well as for the common cold...
was used 5000 years ago in China as a medicinal plant
Herbalism
Herbalism is a traditional medicinal or folk medicine practice based on the use of plants and plant extracts. Herbalism is also known as botanical medicine, medical herbalism, herbal medicine, herbology, herblore, and phytotherapy...
; its active ingredients are alkaloids ephedrine, pseudoephedrine
Pseudoephedrine
Pseudoephedrine is a sympathomimetic drug of the phenethylamine and amphetamine chemical classes. It is used as a nasal/sinus decongestant and stimulant, or as a wakefulness-promoting agent....
, norephedrine (phenylpropanolamine
Phenylpropanolamine
Phenylpropanolamine , also known as the stereoisomers norephedrine and norpseudoephedrine, is a psychoactive drug of the phenethylamine and amphetamine chemical classes which is used as a stimulant, decongestant, and anorectic agent. It is commonly used in prescription and over-the-counter cough...
) and norpseudoephedrine (cathine
Cathine
Cathine, also known as d-norpseudoephedrine, is a psychoactive drug of the phenethylamine and amphetamine chemical classes which acts as a stimulant...
). Natives of Yemen
Yemen
The Republic of Yemen , commonly known as Yemen , is a country located in the Middle East, occupying the southwestern to southern end of the Arabian Peninsula. It is bordered by Saudi Arabia to the north, the Red Sea to the west, and Oman to the east....
and Ethiopia
Ethiopia
Ethiopia , officially known as the Federal Democratic Republic of Ethiopia, is a country located in the Horn of Africa. It is the second-most populous nation in Africa, with over 82 million inhabitants, and the tenth-largest by area, occupying 1,100,000 km2...
have a long tradition of chewing khat
Khat
Khat, qat, gat or Waquish Spoken from true Yemeni, is a flowering plant native to tropical East Africa and the Arabian Peninsula....
leaves to achieve a stimulating effect. The active substances of khat are cathinone and to a lesser extent cathine.
Amphetamine was first synthesized in 1887 by Romania
Romania
Romania is a country located at the crossroads of Central and Southeastern Europe, on the Lower Danube, within and outside the Carpathian arch, bordering on the Black Sea...
n chemist Lazăr Edeleanu
Lazar Edeleanu
Lazăr Edeleanu was a Romanian chemist of Jewish origin.He was the first chemist to synthesize amphetamine at the University of Berlin and the inventor of the modern method of refining crude oil.- His childhood and studies:...
and did not attract special attention. MDMA was produced in 1912 (according to other sources in 1914) as an intermediate product. However, this synthesis also went largely unnoticed. In the 1920s, both methamphetamine and an optical isomer of amphetamine dextroamphetamine
Dextroamphetamine
Dextroamphetamine is a psychostimulant drug which is known to produce increased wakefulness and focus as well as decreased fatigue and decreased appetite....
(D-amphetamines) were synthesized. This synthesis was a by-product of a search for ephedrine, a bronchodialator used to treat asthma
Asthma
Asthma is the common chronic inflammatory disease of the airways characterized by variable and recurring symptoms, reversible airflow obstruction, and bronchospasm. Symptoms include wheezing, coughing, chest tightness, and shortness of breath...
extracted exclusively from natural sources. Over-the-counter use of amphetamines was initiated in early 1930s by the pharmaceutical company Smith, Kline & French (now part of GlaxoSmithKline
GlaxoSmithKline
GlaxoSmithKline plc is a global pharmaceutical, biologics, vaccines and consumer healthcare company headquartered in London, United Kingdom...
), as a medicine (Benzedrine
Benzedrine
Benzedrine is the trade name of the racemic mixture of amphetamine . It was marketed under this brandname in the USA by Smith, Kline & French in the form of inhalers, starting in 1928...
) for cold
Cold
Cold describes the condition of low temperature.Cold may also refer to:*Common cold, a contagious viral infectious disease of the upper respiratory system*Chronic obstructive pulmonary disease...
s and nasal congestion
Nasal congestion
Nasal congestion is the blockage of the nasal passages usually due to membranes lining the nose becoming swollen from inflamed blood vessels. It is also known as nasal blockage, nasal obstruction, blocked nose, stuffy nose, or stuffed up nose.Nasal congestion has many causes and can range from a...
. Subsequently, amphetamine was used in the treatment of narcolepsy
Narcolepsy
Narcolepsy is a chronic sleep disorder, or dyssomnia, characterized by excessive sleepiness and sleep attacks at inappropriate times, such as while at work. People with narcolepsy often experience disturbed nocturnal sleep and an abnormal daytime sleep pattern, which often is confused with insomnia...
, obesity
Obesity
Obesity is a medical condition in which excess body fat has accumulated to the extent that it may have an adverse effect on health, leading to reduced life expectancy and/or increased health problems...
, hay fever
Allergic rhinitis
Allergic rhinitis, also known as pollenosis or hay fever, is an allergic inflammation of the nasal airways.It occurs when an allergen, such as pollen, dust or animal dander is inhaled by an individual with a sensitized immune system...
, orthostatic hypotension
Orthostatic hypotension
Orthostatic hypotension, also known as postural hypotension, orthostasis, and colloquially as head rush or dizzy spell, is a form of hypotension in which a person's blood pressure suddenly falls when the person stands up or stretches. The decrease is typically greater than 20/10 mm Hg, and may be...
, epilepsy
Epilepsy
Epilepsy is a common chronic neurological disorder characterized by seizures. These seizures are transient signs and/or symptoms of abnormal, excessive or hypersynchronous neuronal activity in the brain.About 50 million people worldwide have epilepsy, and nearly two out of every three new cases...
, Parkinson's disease
Parkinson's disease
Parkinson's disease is a degenerative disorder of the central nervous system...
, alcoholism
Alcoholism
Alcoholism is a broad term for problems with alcohol, and is generally used to mean compulsive and uncontrolled consumption of alcoholic beverages, usually to the detriment of the drinker's health, personal relationships, and social standing...
and migraine
Migraine
Migraine is a chronic neurological disorder characterized by moderate to severe headaches, and nausea...
. The "reinforcing" effects of amphetamines were quickly discovered, and the misuse of amphetamines had been noted as far back as 1936.
During World War II
World War II
World War II, or the Second World War , was a global conflict lasting from 1939 to 1945, involving most of the world's nations—including all of the great powers—eventually forming two opposing military alliances: the Allies and the Axis...
, amphetamines were used by the German military to keep their tank crews awake for long periods, and treat depression
Depression (mood)
Depression is a state of low mood and aversion to activity that can affect a person's thoughts, behaviour, feelings and physical well-being. Depressed people may feel sad, anxious, empty, hopeless, helpless, worthless, guilty, irritable, or restless...
. It was noticed that extended rest was required after such artificially induced activity.
The widespread use of amphetamines began in the postwar Japan
Japan
Japan is an island nation in East Asia. Located in the Pacific Ocean, it lies to the east of the Sea of Japan, China, North Korea, South Korea and Russia, stretching from the Sea of Okhotsk in the north to the East China Sea and Taiwan in the south...
and quickly spread to other countries. Modified ("designer"), amphetamines gained popularity since 1960s, such as MDA
3,4-Methylenedioxyamphetamine
3,4-Methylenedioxyamphetamine , also known as tenamfetamine , is a psychedelic and entactogenic drug of the phenethylamine and amphetamine chemical classes...
and PMA. MDMA was rediscovered and popularized by the American chemist Alexander Shulgin
Alexander Shulgin
Alexander "Sasha" Theodore Shulgin is an American pharmacologist, chemist, artist, and drug developer.Shulgin is credited with the popularization of MDMA, commonly known as ecstasy, in the late 1970s and early 1980s, especially for psychopharmaceutical use and the treatment of depression and...
in 1965, after which it was used for some time in psychotherapy
Psychotherapy
Psychotherapy is a general term referring to any form of therapeutic interaction or treatment contracted between a trained professional and a client or patient; family, couple or group...
sessions. In 1970, the United States
United States
The United States of America is a federal constitutional republic comprising fifty states and a federal district...
adopted "the Controlled Substances Act" that limited non-medical use of amphetamines. Street use of PMA was noted in 1972, and in 1985, MDMA was banned by the US authorities in an emergency scheduling initiated by the US Drug Enforcement Agency.
Since the mid 1990s, MDMA ("ecstasy") became a popular entactogenic drug among the youth and quite often non-MDMA substances were sold as "ecstasy". In the first legally sanctioned trials in the USA in over twenty years, the safety profile of MDMA has been demonstrated, and it has been shown to be a successful adjunct to psychotherapy in the management of treatment-resistant Post-Traumatic Stress Disorder (PTSD) in victims of sexual abuse and sufferers of other conditions.
Structure
Amphetamines are a subgroup of the substituted phenethylamineSubstituted phenethylamine
The substituted phenethylamines are chemical compounds with the 2-phenethylamine chemical structure modified at the phenyl ring, sidechain, and/or amino group. Some of them are psychoactive drugs, including stimulants, psychedelics, opioids, and entactogens, which exert their effects primarily...
class of compounds. Substitution of hydrogen atoms results in a large class of compounds. Typical reaction is substitution by methyl and sometimes ethyl group
Ethyl group
In chemistry, an ethyl group is an alkyl substituent derived from ethane . It has the formula -C2H5 and is very often abbreviated -Et.Ethylation is the formation of a compound by introduction of the ethyl functional group, C2H5....
s at the amine
Amine
Amines are organic compounds and functional groups that contain a basic nitrogen atom with a lone pair. Amines are derivatives of ammonia, wherein one or more hydrogen atoms have been replaced by a substituent such as an alkyl or aryl group. Important amines include amino acids, biogenic amines,...
and phenyl
Phenyl group
In organic chemistry, the phenyl group or phenyl ring is a cyclic group of atoms with the formula C6H5. Phenyl groups are closely related to benzene. Phenyl groups have six carbon atoms bonded together in a hexagonal planar ring, five of which are bonded to individual hydrogen atoms, with the...
sites:
| Substance | Substitutes | Structure | ||||||
|---|---|---|---|---|---|---|---|---|
| N | α | β | phenyl group Phenyl group In organic chemistry, the phenyl group or phenyl ring is a cyclic group of atoms with the formula C6H5. Phenyl groups are closely related to benzene. Phenyl groups have six carbon atoms bonded together in a hexagonal planar ring, five of which are bonded to individual hydrogen atoms, with the... |
|||||
| 2 | 3 | 4 | 5 | |||||
| Amphetamine Amphetamine Amphetamine or amfetamine is a psychostimulant drug of the phenethylamine class which produces increased wakefulness and focus in association with decreased fatigue and appetite.Brand names of medications that contain, or metabolize into, amphetamine include Adderall, Dexedrine, Dextrostat,... (α-methylphenylethylamine) |
-CH3 |  |
||||||
| Methamphetamine Methamphetamine Methamphetamine is a psychostimulant of the phenethylamine and amphetamine class of psychoactive drugs... (N-methylamphetamine) |
-CH3 | -CH3 |  |
|||||
| Ephedrine Ephedrine Ephedrine is a sympathomimetic amine commonly used as a stimulant, appetite suppressant, concentration aid, decongestant, and to treat hypotension associated with anaesthesia.... pseudoephedrine Pseudoephedrine Pseudoephedrine is a sympathomimetic drug of the phenethylamine and amphetamine chemical classes. It is used as a nasal/sinus decongestant and stimulant, or as a wakefulness-promoting agent.... |
-CH3 | -CH3 | -OH | |||||
| Cathinone Cathinone Cathinone, or Benzoylethanamine, is a monoamine alkaloid found in the shrub Catha edulis and is chemically similar to ephedrine, cathine and other amphetamines. Cathinone induces the release of dopamine from striatal preparations that are prelabelled either with dopamine or its precursors. It is... |
-CH3 | =O | ||||||
| Methcathinone Methcathinone Methcathinone , is a psychoactive stimulant, sometimes used as a recreational drug and considered addictive. It is usually snorted, but can be smoked, injected, or taken orally... (ephedrone) |
-CH3 | -CH3 | =O | |||||
| MDA 3,4-Methylenedioxyamphetamine 3,4-Methylenedioxyamphetamine , also known as tenamfetamine , is a psychedelic and entactogenic drug of the phenethylamine and amphetamine chemical classes... (3,4-methylenedioxyamphetamine) |
-CH3 | -O-CH2-O- |  |
|||||
| MDMA (3,4-methylenedioxymethamphetamine) | -CH3 | -CH3 | -O-CH2-O- | |||||
| MDEA Methylenedioxyethylamphetamine 3,4-Methylenedioxy-N-ethylamphetamine is an entactogen, psychedelic, and stimulant of the phenethylamine and amphetamine chemical classes.... (3,4-methylenedioxy-N-ethylamphetamine) |
-CH2-CH3 | -CH3 | -O-CH2-O- | |||||
| EDMA EDMA 3,4-Ethylenedioxy-N-methylamphetamine is an entactogen drug of the amphetamine class. It is an analogue of MDMA where the methylenedioxy ring has been replaced by an ethylenedioxy ring. EDMA was first synthesized by Alexander Shulgin. In his book PiHKAL, the dosage is listed as 150–250 mg,... (3,4-ethylenedioxy-N-methylamphetamine) |
-CH3 | -CH3 | -O-CH2-CH2-O- | |||||
| MBDB MBDB Methylbenzodioxolylbutanamine is an entactogen of the phenethylamine chemical class. MBDB is a closely related chemical analogue of MDMA, with the only difference between the two molecules being an ethyl group instead of a methyl group attached to the alpha carbon.MBDB was first synthesized by... (N-methyl-1-(3,4-methylenedioxyphenyl)-2-aminobutane) |
-CH3 | -CH2-CH3 | -O-CH2-O- |  |
||||
| PMA (para-metoxyamphetamine) | -CH3 | -O-CH3 |  |
|||||
| PMMA (para-metoxymetamphetamine) | -CH3 | -CH3 | -O-CH3 |  |
||||
| 4-MTA (4-methylthioamphetamine) | -CH3 | -S-CH3 |  |
|||||
| 3,4-DMA Dimethoxyamphetamine DMA, or dimethoxyamphetamine, is a series of lesser-known psychedelic drugs similar in structure to amphetamine and to trimethoxyamphetamine . They were first synthesized by Alexander Shulgin and written up in his book PiHKAL ... (3,4-dimetoxyamphetamine) |
-CH3 | -O-CH3 | -O-CH3 |  |
||||
| 3,4,5-TMA Trimethoxyamphetamine TMAs, also known as trimethoxyamphetamines, are a family of isomeric psychedelic hallucinogenic drugs. There exist six different TMAs that differ only in the position of the three methoxy groups: TMA, TMA-2, TMA-3, TMA-4, TMA-5, and TMA-6. The TMAs are analogs of the phenethylamine cactus alkaloid... (3,4,5-trimetoxyamphetamine, α-methylmescaline) |
-CH3 | -O-CH3 | -O-CH3 | -O-CH3 | ||||
| DOM 2,5-Dimethoxy-4-methylamphetamine 2,5-Dimethoxy-4-methylamphetamine is a psychedelic and a substituted amphetamine... (2,5-dimethoxy-4-methylamphetamine) |
-CH3 | -O-CH3 | -CH3 | -O-CH3 | ||||
| DOB 2,5-Dimethoxy-4-bromoamphetamine DOB, also known as Brolamfetamine and Bromo-DMA, is a psychedelic hallucinogenic drug and a substituted amphetamine of the phenethylamine class of compounds, which can be used as an entheogen. DOB was first synthesized by Alexander Shulgin in 1967... (2,5-dimethoxy-4-bromoamphetamine) |
-CH3 | -O-CH3 | -Br | -O-CH3 |  |
|||
Classification of central effects
Effects of amphetamines on the central nervous systemCentral nervous system
The central nervous system is the part of the nervous system that integrates the information that it receives from, and coordinates the activity of, all parts of the bodies of bilaterian animals—that is, all multicellular animals except sponges and radially symmetric animals such as jellyfish...
are diverse and can be attributed to the three main classes:
- PsychoanalepticPsychoanalepticIn pharmacology, a psychoanaleptic is a medication that produces an arousing effect upon the patient.Antidepressants, psychostimulants, agents used for ADHD and nootropics, and Anti-dementia drugs are all psychoanaleptics....
- HallucinogenicPsychedelics, dissociatives and deliriantsThis general group of pharmacological agents can be divided into three broad categories: psychedelics, dissociatives, and deliriants. These classes of psychoactive drugs have in common that they can cause subjective changes in perception, thought, emotion and consciousness...
- EmpathogenicEmpathogen-entactogenThe terms empathogen and entactogen are used to describe a class of psychoactive drugs that produce distinctive emotional and social effects similar to those of MDMA. Putative members of this class include 2C-B, 2C-I, MDMA, MDA, MDEA, MBDB, 2C-T-7, and 2C-T-2, among others...
– creating a sense of well-being, openness and empathy to others.
Studies on animals have shown that these classes of effects are independent. Various amphetamines may cause these actions, either separately or in combination; for example, amphetamine adds hallucination
Hallucination
A hallucination, in the broadest sense of the word, is a perception in the absence of a stimulus. In a stricter sense, hallucinations are defined as perceptions in a conscious and awake state in the absence of external stimuli which have qualities of real perception, in that they are vivid,...
effect at high doses (amphetamine psychosis), however this is quite different than the 'hallucinongenic' phenomena that are typically associated with what are often commonly referred to as the psychedelic amphetamines. The stimulating effect of amphetamine is similar to that of cocaine
Cocaine
Cocaine is a crystalline tropane alkaloid that is obtained from the leaves of the coca plant. The name comes from "coca" in addition to the alkaloid suffix -ine, forming cocaine. It is a stimulant of the central nervous system, an appetite suppressant, and a topical anesthetic...
, but lasts longer.
Mechanisms
The stimulating effect of amphetamines is mainly associated with an increased emissions of catecholamines norepinephrineNorepinephrine
Norepinephrine is the US name for noradrenaline , a catecholamine with multiple roles including as a hormone and a neurotransmitter...
and dopamine
Dopamine
Dopamine is a catecholamine neurotransmitter present in a wide variety of animals, including both vertebrates and invertebrates. In the brain, this substituted phenethylamine functions as a neurotransmitter, activating the five known types of dopamine receptors—D1, D2, D3, D4, and D5—and their...
. In the normal operation, synaptic release of catecholamines is carried out by exocytosis
Exocytosis
Exocytosis , also known as 'The peni-cytosis', is the durable process by which a cell directs the contents of secretory vesicles out of the cell membrane...
of a vesicle which contain a neurotransmitter
Neurotransmitter
Neurotransmitters are endogenous chemicals that transmit signals from a neuron to a target cell across a synapse. Neurotransmitters are packaged into synaptic vesicles clustered beneath the membrane on the presynaptic side of a synapse, and are released into the synaptic cleft, where they bind to...
. Then, the neurotransmitter is reabsorbed
Reuptake
Reuptake, or re-uptake, is the reabsorption of a neurotransmitter by a neurotransmitter transporter of a pre-synaptic neuron after it has performed its function of transmitting a neural impulse....
from the synaptic cleft into the cytoplasm of the neuron. From the cytoplasm, the neurotransmitter penetrates back into the vesicles via the action of the vesicular monoamine transporter
Vesicular monoamine transporter
The vesicular monoamine transporter is a transport protein integrated into the membrane of intracellular vesicles of presynaptic neurons. It acts to transport monoamines into the synaptic vesicles.-Monoamines:...
(VMAT).
Presence of amphetamine and its derivative inverts the direction of the transport: neurotransmitter moves from vesicles to the cytoplasm and then to the synaptic cleft. As a result, vesicles are emptied, vesicular release of neurotransmitter is reduced, and the concentration of neurotransmitter in the synaptic cleft increases. In this three mechanisms are utilized:
Inhibitors of reuptake of monoamines, such as cocaine
Cocaine
Cocaine is a crystalline tropane alkaloid that is obtained from the leaves of the coca plant. The name comes from "coca" in addition to the alkaloid suffix -ine, forming cocaine. It is a stimulant of the central nervous system, an appetite suppressant, and a topical anesthetic...
, reduce the emission of monoamines, caused by amphetamine-type stimulants. Effects of hallucinogenic amphetamines is similar to other classical hallucinogens and is related to their agonism
Agonist
An agonist is a chemical that binds to a receptor of a cell and triggers a response by that cell. Agonists often mimic the action of a naturally occurring substance...
to serotonin
Serotonin
Serotonin or 5-hydroxytryptamine is a monoamine neurotransmitter. Biochemically derived from tryptophan, serotonin is primarily found in the gastrointestinal tract, platelets, and in the central nervous system of animals including humans...
receptor of the type 5-HT2A
5-HT2A receptor
The mammalian 5-HT2A receptor is a subtype of the 5-HT2 receptor that belongs to the serotonin receptor family and is a G protein-coupled receptor . This is the main excitatory receptor subtype among the GPCRs for serotonin , although 5-HT2A may also have an inhibitory effect on certain areas such...
. Also, lesser-known mechanisms possibly associated with hallucinogenic effects (in traditional plain stimulant and non-hallucinogen class amphetamines) may potentially include agonism of the trace amine-associated receptor
Trace amine-associated receptor
Trace amine-associated receptors, abbreviated TAAR and otherwise known as trace amine receptors, abbreviated TAR or TA, are a class of G protein-coupled receptors identified in 2001....
s (TAARs) and other functions of the amphetamine molecular skeleton in the CNS.
Structure-Activity Relationships
There is a relationship between the chemical structure of the amphetamine compound and its effects. Substitutions of the amino group enhance the stimulating effect of the substance, but may reduce other actions. Examples include methamphetamine and N-hydroxyamphetamine, which are more powerful stimulants than amphetamine.Replacing methyl group
Methyl group
Methyl group is a functional group derived from methane, containing one carbon atom bonded to three hydrogen atoms —CH3. The group is often abbreviated Me. Such hydrocarbon groups occur in many organic compounds. The methyl group can be found in three forms: anion, cation and radical. The anion...
in the position α to ethyl group reduces the stimulating and hallucinogenic actions, but does not affect the empathogenic action (as in MBDB
MBDB
Methylbenzodioxolylbutanamine is an entactogen of the phenethylamine chemical class. MBDB is a closely related chemical analogue of MDMA, with the only difference between the two molecules being an ethyl group instead of a methyl group attached to the alpha carbon.MBDB was first synthesized by...
) and suppression of appetite (as in phentermine
Phentermine
Phentermine, a contraction of "phenyl-tertiary-butylamine", is a psychostimulant drug of the phenethylamine class, chemically related to amphetamine. It is used medically as an appetite suppressant....
). Removing the methyl group in position α usually decreases the effectiveness of substance; thus, phenethylamine
Phenethylamine
Phenylethylamine or phenethylamine is a natural monoamine alkaloid, trace amine, and also the name of a class of chemicals with many members well known for psychoactive drug and stimulant effects. Studies suggest that phenylethylamine functions as a neuromodulator or neurotransmitter in the...
poorly penetrates the blood-brain barrier
Blood-brain barrier
The blood–brain barrier is a separation of circulating blood and the brain extracellular fluid in the central nervous system . It occurs along all capillaries and consists of tight junctions around the capillaries that do not exist in normal circulation. Endothelial cells restrict the diffusion...
and is rapidly metabolized. Substitutions in the phenyl group
Phenyl group
In organic chemistry, the phenyl group or phenyl ring is a cyclic group of atoms with the formula C6H5. Phenyl groups are closely related to benzene. Phenyl groups have six carbon atoms bonded together in a hexagonal planar ring, five of which are bonded to individual hydrogen atoms, with the...
decrease the stimulating action, but may induce other effects. Substitution in position 4 is usually associated with serotonergic action.
Right-handed (dextrorotatory) enantiomers of amphetamines, such as dextroamphetamine, are usually 4–10 times more potent than left-handed, with the exception for MDMA and a few related substances whose efficiency does not depend on the isomerism.
Peripheral effect
The effect of amphetamines on the autonomic nervous systemAutonomic nervous system
The autonomic nervous system is the part of the peripheral nervous system that acts as a control system functioning largely below the level of consciousness, and controls visceral functions. The ANS affects heart rate, digestion, respiration rate, salivation, perspiration, diameter of the pupils,...
is mainly due to emissions of norepinephrine
Norepinephrine
Norepinephrine is the US name for noradrenaline , a catecholamine with multiple roles including as a hormone and a neurotransmitter...
. This enhances stimulation of α-and β-adrenoreceptors
Adrenergic receptor
The adrenergic receptors are a class of metabotropic G protein-coupled receptors that are targets of the catecholamines, especially noradrenaline and adrenaline ....
that can lead to tachycardia
Tachycardia
Tachycardia comes from the Greek words tachys and kardia . Tachycardia typically refers to a heart rate that exceeds the normal range for a resting heart rate...
(increased heart rate), elevated blood pressure
Blood pressure
Blood pressure is the pressure exerted by circulating blood upon the walls of blood vessels, and is one of the principal vital signs. When used without further specification, "blood pressure" usually refers to the arterial pressure of the systemic circulation. During each heartbeat, BP varies...
, mydriasis
Mydriasis
Mydriasis is a dilation of the pupil due to disease, trauma or the use of drugs. Normally, the pupil dilates in the dark and constricts in the light to respectively improve vividity at night and to protect the retina from sunlight damage during the day...
(dilated pupils), sweat
SWEAT
SWEAT is an OLN/TSN show hosted by Julie Zwillich that aired in 2003-2004.Each of the 13 half-hour episodes of SWEAT features a different outdoor sport: kayaking, mountain biking, ice hockey, beach volleyball, soccer, windsurfing, rowing, Ultimate, triathlon, wakeboarding, snowboarding, telemark...
ing and hyperthermia
Hyperthermia
Hyperthermia is an elevated body temperature due to failed thermoregulation. Hyperthermia occurs when the body produces or absorbs more heat than it can dissipate...
(elevated body temperature).
Toxicity
Acute toxicity of amphetamines is primarily related with their impact on the central and peripheral adrenergic receptorAdrenergic receptor
The adrenergic receptors are a class of metabotropic G protein-coupled receptors that are targets of the catecholamines, especially noradrenaline and adrenaline ....
s. Regarding central nervous system
Central nervous system
The central nervous system is the part of the nervous system that integrates the information that it receives from, and coordinates the activity of, all parts of the bodies of bilaterian animals—that is, all multicellular animals except sponges and radially symmetric animals such as jellyfish...
, it can manifest itself as psychosis, visual and tactile
Somatosensory system
The somatosensory system is a diverse sensory system composed of the receptors and processing centres to produce the sensory modalities such as touch, temperature, proprioception , and nociception . The sensory receptors cover the skin and epithelia, skeletal muscles, bones and joints, internal...
hallucination
Hallucination
A hallucination, in the broadest sense of the word, is a perception in the absence of a stimulus. In a stricter sense, hallucinations are defined as perceptions in a conscious and awake state in the absence of external stimuli which have qualities of real perception, in that they are vivid,...
and anxiety. The effects on cardiovascular system are expressed as tachycardia and increased blood pressure. The immediate causes of death from the use of amphetamines are usually hyperthermia, heart arrhythmia or stroke
Stroke
A stroke, previously known medically as a cerebrovascular accident , is the rapidly developing loss of brain function due to disturbance in the blood supply to the brain. This can be due to ischemia caused by blockage , or a hemorrhage...
.
Unlike many other drugs, amphetamine and especially methamphetamine are neurotoxic and can irreversibly damage dopaminergic
Dopaminergic
Dopaminergic means related to the neurotransmitter dopamine. For example, certain proteins such as the dopamine transporter , vesicular monoamine transporter 2 , and dopamine receptors can be classified as dopaminergic, and neurons which synthesize or contain dopamine and synapses with dopamine...
and serotonergic
Serotonergic
Serotonergic or serotoninergic means "related to the neurotransmitter serotonin". A synapse is serotonergic if it uses serotonin as its neurotransmitter...
neuron
Neuron
A neuron is an electrically excitable cell that processes and transmits information by electrical and chemical signaling. Chemical signaling occurs via synapses, specialized connections with other cells. Neurons connect to each other to form networks. Neurons are the core components of the nervous...
s. It is believed that the toxic effect of amphetamines on dopaminergic neurons is associated with the formation of free radicals
Radical (chemistry)
Radicals are atoms, molecules, or ions with unpaired electrons on an open shell configuration. Free radicals may have positive, negative, or zero charge...
and peroxynitrite
Peroxynitrite
Peroxynitrite is the anion with the formula ONOO−. It is an unstable structural isomer of nitrate, NO3−, which has the same formula but a different structure. Although peroxynitrous acid is highly reactive, its conjugate base peroxynitrite is stable in basic solution...
, which is a strong oxidizer. MDMA, moreover, reduces concentration of antioxidant
Antioxidant
An antioxidant is a molecule capable of inhibiting the oxidation of other molecules. Oxidation is a chemical reaction that transfers electrons or hydrogen from a substance to an oxidizing agent. Oxidation reactions can produce free radicals. In turn, these radicals can start chain reactions. When...
s glutathione
Glutathione
Glutathione is a tripeptide that contains an unusual peptide linkage between the amine group of cysteine and the carboxyl group of the glutamate side-chain...
and vitamin E
Vitamin E
Vitamin E is used to refer to a group of fat-soluble compounds that include both tocopherols and tocotrienols. There are many different forms of vitamin E, of which γ-tocopherol is the most common in the North American diet. γ-Tocopherol can be found in corn oil, soybean oil, margarine and dressings...
in the brain, and is therefore neurotoxic in high doses. Whether or not MDMA is neurotoxic as a result of prolonged use in normal doses is being debated.
Dependence
After prolonged use, amphetamines, except for classical hallucinogens, can induce strong addictionAddiction
Historically, addiction has been defined as physical and psychological dependence on psychoactive substances which cross the blood-brain barrier once ingested, temporarily altering the chemical milieu of the brain.Addiction can also be viewed as a continued involvement with a substance or activity...
that can last up to several weeks. Some energy drinks contain small levels of amphetamines depending on size and quantity; which can be mistaken in few drug test, depending on time, and amount of consumption. It is believed that psychological dependence on amphetamines, as well as on other drugs, is associated with stimulation by the drug of dopaminergic neurons in the ventral tegmental area. Those neurons are responsible for feelings of reward that affect the processes of learning and adaptation.
Physical dependence on amphetamine-type stimulants is controversial. Interruption after their prolonged use results in fatigue, depression
Depression (mood)
Depression is a state of low mood and aversion to activity that can affect a person's thoughts, behaviour, feelings and physical well-being. Depressed people may feel sad, anxious, empty, hopeless, helpless, worthless, guilty, irritable, or restless...
, sleepiness and feeling of hunger
Hunger
Hunger is the most commonly used term to describe the social condition of people who frequently experience the physical sensation of desiring food.-Malnutrition, famine, starvation:...
. These symptoms may be regarded as components of withdrawal syndrome
Withdrawal syndrome
A withdrawal syndrome, also called a discontinuation syndrome, occurs when a person suddenly stops taking or reduces the dosage of some types of medications...
or just as normal response of the body to the lack of sleep and food that accompanies systematic use of amphetamine-type stimulants.
Classic hallucinogens (such as DOM
2,5-Dimethoxy-4-methylamphetamine
2,5-Dimethoxy-4-methylamphetamine is a psychedelic and a substituted amphetamine...
) do not cause addiction. Laboratory animals which were taught to use stimulants did not use hallucinogens on their own initiative.
Production, distribution and use
Free bases of amphetamines are liquids with limited resistance. Therefore, amphetamines are distributed as salts (sulfateSulfate
In inorganic chemistry, a sulfate is a salt of sulfuric acid.-Chemical properties:...
s, phosphate
Phosphate
A phosphate, an inorganic chemical, is a salt of phosphoric acid. In organic chemistry, a phosphate, or organophosphate, is an ester of phosphoric acid. Organic phosphates are important in biochemistry and biogeochemistry or ecology. Inorganic phosphates are mined to obtain phosphorus for use in...
s and chloride
Chloride
The chloride ion is formed when the element chlorine, a halogen, picks up one electron to form an anion Cl−. The salts of hydrochloric acid HCl contain chloride ions and can also be called chlorides. The chloride ion, and its salts such as sodium chloride, are very soluble in water...
s). Amphetamine is usually sold as tablets and sometimes as capsules or syrup. Methamphetamine is usually available as a powder for inhalation or preparing a solution for intravenous injection, and less often as tablets or capsules. Also common is crystalline methamphetamine hydrochloride intended for smoking. Methylenedioxyamphetamines (MDMA, MDEA) are usually tablets.
Amphetamines have good bioavailability
Bioavailability
In pharmacology, bioavailability is a subcategory of absorption and is used to describe the fraction of an administered dose of unchanged drug that reaches the systemic circulation, one of the principal pharmacokinetic properties of drugs. By definition, when a medication is administered...
upon oral or intranasal administration. Because of their lipophilicity, amphetamines easily penetrate the blood-brain barrier
Blood-brain barrier
The blood–brain barrier is a separation of circulating blood and the brain extracellular fluid in the central nervous system . It occurs along all capillaries and consists of tight junctions around the capillaries that do not exist in normal circulation. Endothelial cells restrict the diffusion...
. A typical oral dose is 5–20 mg for amphetamine and methamphetamine., 80–150 mg for MDA and MDMA, 3–10 mg for DOM
2,5-Dimethoxy-4-methylamphetamine
2,5-Dimethoxy-4-methylamphetamine is a psychedelic and a substituted amphetamine...
and 1–3 mg for DOB
2,5-Dimethoxy-4-bromoamphetamine
DOB, also known as Brolamfetamine and Bromo-DMA, is a psychedelic hallucinogenic drug and a substituted amphetamine of the phenethylamine class of compounds, which can be used as an entheogen. DOB was first synthesized by Alexander Shulgin in 1967...
. Biological half-life
Biological half-life
The biological half-life or elimination half-life of a substance is the time it takes for a substance to lose half of its pharmacologic, physiologic, or radiologic activity, as per the MeSH definition...
is 8–30 h for amphetamine, 12–34 h for methamphetamine and 5–10 h for MDMA.
The action of amphetamines usually lasts 4–6 hours, but in some cases up to 24 hours.
Treatment of amphetamine poisoning and addiction
One of the most dangerous manifestations of overdose with amphetamine-type stimulants are hyperthermia and hyperactivity which can cause various types of damage in skeletal muscles. Therefore, first aid in such overdose cases includes the physical immobilization of the patient, to prevent possible harm to the patient or others, and sedationSedation
Sedation is the reduction of irritability or agitation by administration of sedative drugs, generally to facilitate a medical procedure or diagnostic procedure...
by intravenous injection. Hyperthermia is reduced with external cooling and some measures might be taken to increase urination, in order to excrete the poison.
Treatment of addiction to amphetamine and its derivatives are similar to those for other stimulants such as cocaine. Because of the weak physical effect of amphetamine addiction, the use of amphetamines is interrupted abruptly instead of gradually reducing the drug dose.
The major symptoms of psychological addiction are depression, feeling of boredom and nostalgia for the pleasure associated with the drug. The treatment is usually based on individual work with the patient and the patient's desire to quit drug use. Despite ongoing intensive search, by 2008, efficient medical treatment has not been available. Although the tests are far from complete, some positive results were achieved with the following drugs:
- DextroamphetamineDextroamphetamineDextroamphetamine is a psychostimulant drug which is known to produce increased wakefulness and focus as well as decreased fatigue and decreased appetite....
, methylphenidateMethylphenidateMethylphenidate is a psychostimulant drug approved for treatment of attention-deficit hyperactivity disorder, postural orthostatic tachycardia syndrome and narcolepsy. It may also be prescribed for off-label use in treatment-resistant cases of lethargy, depression, neural insult and obesity...
and modafinilModafinilModafinil is an analeptic drug manufactured by Cephalon, and is approved by the U.S. Food and Drug Administration for the treatment of narcolepsy, shift work sleep disorder, and excessive daytime sleepiness associated with obstructive sleep apnea...
(stimulants); - BupropionBupropionBupropion is an atypical antidepressant and smoking cessation aid. The drug is a non-tricyclic antidepressant and differs from most commonly prescribed antidepressants such as SSRIs, as its primary pharmacological action is thought to be norepinephrine-dopamine reuptake inhibition...
(an antidepressant); - RisperidoneRisperidoneRisperidone is a second generation or atypical antipsychotic, sold under the trade name . It is used to treat schizophrenia , schizoaffective disorder, the mixed and manic states associated with bipolar disorder, and irritability in people with autism...
(antipsychotic); - RivastigmineRivastigmineRivastigmine is a parasympathomimetic or cholinergic agent for the treatment of mild to moderate dementia of the Alzheimer’s type and dementia due to Parkinson's disease. The drug can be administered orally or via a transdermal patch; the latter form reduces the prevalence of side effects, which...
(an inhibitor of acetylcholinesterase); - LobelineLobelineLobeline is a natural alkaloid found in "Indian tobacco" , "Devil's tobacco" , "cardinal flower" , "great lobelia" , and Hippobroma longiflora...
(an inhibitor of dopamine reuptake).
Synthesis
Most amphetamines are syntheticChemical synthesis
In chemistry, chemical synthesis is purposeful execution of chemical reactions to get a product, or several products. This happens by physical and chemical manipulations usually involving one or more reactions...
compounds. Exceptions include cathinone which is present in khat leaves and ephedrine and pseudoephedrine
Pseudoephedrine
Pseudoephedrine is a sympathomimetic drug of the phenethylamine and amphetamine chemical classes. It is used as a nasal/sinus decongestant and stimulant, or as a wakefulness-promoting agent....
, the active components of Ephedra
Ephedra
Ephedra refers to the plant Ephedra sinica. E. sinica, known in Chinese as ma huang , has been used in traditional Chinese medicine for 5,000 years for the treatment of asthma and hay fever, as well as for the common cold...
. These natural alkaloids have a much weaker effect than the amphetamine.
From ephedrine and its derivatives
Methamphetamine can be obtained through one of the following redoxRedox
Redox reactions describe all chemical reactions in which atoms have their oxidation state changed....
reactions of ephedrine. Ephedrine itself can be extracted from Ephedra
Ephedra
Ephedra refers to the plant Ephedra sinica. E. sinica, known in Chinese as ma huang , has been used in traditional Chinese medicine for 5,000 years for the treatment of asthma and hay fever, as well as for the common cold...
.
- Conversion of ephedrine to chloroephedrine using thionyl chlorideThionyl chlorideThionyl chloride is an inorganic compound with the formula SOCl2. It is a reactive chemical reagent used in chlorination reactions. It is a colorless, distillable liquid at room temperature and pressure that decomposes above 140 °C. Thionyl chloride is sometimes confused with sulfuryl...
(SOCl2), followed by catalyticCatalysisCatalysis is the change in rate of a chemical reaction due to the participation of a substance called a catalyst. Unlike other reagents that participate in the chemical reaction, a catalyst is not consumed by the reaction itself. A catalyst may participate in multiple chemical transformations....
hydrogenationHydrogenationHydrogenation, to treat with hydrogen, also a form of chemical reduction, is a chemical reaction between molecular hydrogen and another compound or element, usually in the presence of a catalyst. The process is commonly employed to reduce or saturate organic compounds. Hydrogenation typically...
. The most catalysts for this reaction are palladiumPalladiumPalladium is a chemical element with the chemical symbol Pd and an atomic number of 46. It is a rare and lustrous silvery-white metal discovered in 1803 by William Hyde Wollaston. He named it after the asteroid Pallas, which was itself named after the epithet of the Greek goddess Athena, acquired...
or platinumPlatinumPlatinum is a chemical element with the chemical symbol Pt and an atomic number of 78. Its name is derived from the Spanish term platina del Pinto, which is literally translated into "little silver of the Pinto River." It is a dense, malleable, ductile, precious, gray-white transition metal...
);
- Reduction of ephedrine using hydroiodic acid in the presence of red phosphorus.
Similarly, from norephedrine (phenylpropanolamine) can be obtained from amphetamine. Methcathinone
Methcathinone
Methcathinone , is a psychoactive stimulant, sometimes used as a recreational drug and considered addictive. It is usually snorted, but can be smoked, injected, or taken orally...
(the n-methyl homologue of cathinone) can be obtained by oxidation of ephedrine with potassium permanganate
Potassium permanganate
Potassium permanganate is an inorganic chemical compound with the formula KMnO4. It is a salt consisting of K+ and MnO4− ions. Formerly known as permanganate of potash or Condy's crystals, it is a strong oxidizing agent. It dissolves in water to give intensely purple solutions, the...
in the presence of acetic acid
Acetic acid
Acetic acid is an organic compound with the chemical formula CH3CO2H . It is a colourless liquid that when undiluted is also called glacial acetic acid. Acetic acid is the main component of vinegar , and has a distinctive sour taste and pungent smell...
. Cathinone can be produced by a similar oxidation of phenylpropanolamine
Phenylpropanolamine
Phenylpropanolamine , also known as the stereoisomers norephedrine and norpseudoephedrine, is a psychoactive drug of the phenethylamine and amphetamine chemical classes which is used as a stimulant, decongestant, and anorectic agent. It is commonly used in prescription and over-the-counter cough...
(norephedrine).
From safrole
SafroleSafrole
Safrole, also known as shikimol, is a phenylpropene. It is a colorless or slightly yellow oily liquid. It is typically extracted from the root-bark or the fruit of sassafras plants in the form of sassafras oil , or synthesized from other related methylenedioxy...
– the main component of the Sassafras
Sassafras
Sassafras is a genus of three extant and one extinct species of deciduous trees in the family Lauraceae, native to eastern North America and eastern Asia.-Overview:...
oil – is used for the synthesis of MDA, MDMA and other amphetamines containing methylenedioxyphenyl group as follows:
- Reaction of Safrole with hexamineHexamineHexamethylenetetramine is a heterocyclic organic compound with the formula 6N4. This white crystalline compound is highly soluble in water and polar organic solvents. It has a cage-like structure similar to adamantane. It is useful in the synthesis of other chemical compounds, e.g. plastics,...
in the presence of sodium iodideSodium iodideSodium iodide is a white, crystalline salt with chemical formula NaI used in radiation detection, treatment of iodine deficiency, and as a reactant in the Finkelstein reaction.-Uses:Sodium iodide is commonly used to treat and prevent iodine deficiency....
results in MDA3,4-Methylenedioxyamphetamine3,4-Methylenedioxyamphetamine , also known as tenamfetamine , is a psychedelic and entactogenic drug of the phenethylamine and amphetamine chemical classes...
; - Reaction with methanolMethanolMethanol, also known as methyl alcohol, wood alcohol, wood naphtha or wood spirits, is a chemical with the formula CH3OH . It is the simplest alcohol, and is a light, volatile, colorless, flammable liquid with a distinctive odor very similar to, but slightly sweeter than, ethanol...
solution of ammoniaAmmoniaAmmonia is a compound of nitrogen and hydrogen with the formula . It is a colourless gas with a characteristic pungent odour. Ammonia contributes significantly to the nutritional needs of terrestrial organisms by serving as a precursor to food and fertilizers. Ammonia, either directly or...
at high temperature and pressure also yields MDA; similar reactions with methylamineMethylamineMethylamine is the organic compound with a formula of CH3NH2. This colourless gas is a derivative of ammonia, but with one H atom replaced by a methyl group. It is the simplest primary amine. It is sold as a solution in methanol, ethanol, THF, and water, or as the anhydrous gas in pressurized...
and ethylamineEthylamineEthylamine is an organic compound with the formula CH3CH2NH2. This colourless gas has a strong ammonia-like odor. It is miscible with virtually all solvents and is considered to be a weak base, as is typical for amines. Ethylamine is widely used in chemical industry and organic...
result, respectively, in MDMA and MDEA.
From phenyl-2-propanone (P2P) and its derivatives
Methamphetamine can be produced by reacting phenyl-2-propanone and (P2P) with methylamine in the presence of aluminiumAluminium
Aluminium or aluminum is a silvery white member of the boron group of chemical elements. It has the symbol Al, and its atomic number is 13. It is not soluble in water under normal circumstances....
amalgam
Amalgam (chemistry)
An amalgam is a substance formed by the reaction of mercury with another metal. Almost all metals can form amalgams with mercury, notable exceptions being iron and platinum. Silver-mercury amalgams are important in dentistry, and gold-mercury amalgam is used in the extraction of gold from ore.The...
.
P2P itself is usually obtained from phenylacetic acid
Phenylacetic acid
Phenylacetic acid is an organic compound containing a phenyl functional group and a carboxylic acid functional group. It is a white solid with a disagreeable odor...
and acetic anhydride
Acetic anhydride
Acetic anhydride, or ethanoic anhydride, is the chemical compound with the formula 2O. Commonly abbreviated Ac2O, it is the simplest isolatable acid anhydride and is a widely used reagent in organic synthesis...
.
Similarly, MDA or MDMA can be produced from 3,4-methylenedioxyphenyl-2-propanone (MDP2P
MDP2P
3,4-phenyl-2-propanone , is a chemical compound consisting of a phenylacetone moiety substituted with a methylenedioxy functional group, an entactogen and stimulant of the phenethylamine, amphetamine, and cathinone classes...
), and the MDP2P can be obtained from piperonal
Piperonal
Piperonal, also known as heliotropin, is an aromatic aldehyde that comes as transparent crystals, C8H6O3, and has a floral odor commonly described as being similar to that of vanillin and cherry. It is used as flavoring and in perfume. It can be obtained by oxidation of piperonyl alcohol or the...
.
From benzaldehyde and its derivatives
Amphetamines can be synthesized by condensation of benzaldehydeBenzaldehyde
Benzaldehyde is an organic compound consisting of a benzene ring with a formyl substituent. It is the simplest aromatic aldehyde and one of the most industrially useful. This colorless liquid has a characteristic pleasant almond-like odor...
with nitroethane
Nitroethane
Nitroethane is an organic compound having the chemical formula C2H5NO2. Similar in many regards to nitromethane, nitroethane is an oily liquid at standard temperature and pressure. Pure nitroethane is colourless and has a fruity odor.- Preparation :...
using amine
Amine
Amines are organic compounds and functional groups that contain a basic nitrogen atom with a lone pair. Amines are derivatives of ammonia, wherein one or more hydrogen atoms have been replaced by a substituent such as an alkyl or aryl group. Important amines include amino acids, biogenic amines,...
as a catalyst, followed by reduction using, e.g. lithium aluminum hydride. Derivatives of benzaldehyde are used in reactions occurring via substitution of the phenyl group of benzaldehyde. For example, piperonal
Piperonal
Piperonal, also known as heliotropin, is an aromatic aldehyde that comes as transparent crystals, C8H6O3, and has a floral odor commonly described as being similar to that of vanillin and cherry. It is used as flavoring and in perfume. It can be obtained by oxidation of piperonyl alcohol or the...
is used for preparing MDA, and it can in turn be extracted as alkaloid piperine
Piperine
Piperine is the alkaloid responsible for the pungency of black pepper and long pepper, along with chavicine . It has also been used in some forms of traditional medicine and as an insecticide. Piperine forms monoclinic needles, is slightly soluble in water and more so in alcohol, ether or...
present in black pepper
Black pepper
Black pepper is a flowering vine in the family Piperaceae, cultivated for its fruit, which is usually dried and used as a spice and seasoning. The fruit, known as a peppercorn when dried, is approximately in diameter, dark red when fully mature, and, like all drupes, contains a single seed...
.
Market
Methylphenidate
Methylphenidate is a psychostimulant drug approved for treatment of attention-deficit hyperactivity disorder, postural orthostatic tachycardia syndrome and narcolepsy. It may also be prescribed for off-label use in treatment-resistant cases of lethargy, depression, neural insult and obesity...
(Ritalin) are used in the treatment of narcolepsy
Narcolepsy
Narcolepsy is a chronic sleep disorder, or dyssomnia, characterized by excessive sleepiness and sleep attacks at inappropriate times, such as while at work. People with narcolepsy often experience disturbed nocturnal sleep and an abnormal daytime sleep pattern, which often is confused with insomnia...
and attention-deficit hyperactivity disorder
Attention-deficit hyperactivity disorder
Attention deficit hyperactivity disorder is a developmental disorder. It is primarily characterized by "the co-existence of attentional problems and hyperactivity, with each behavior occurring infrequently alone" and symptoms starting before seven years of age.ADHD is the most commonly studied and...
. Bupropion
Bupropion
Bupropion is an atypical antidepressant and smoking cessation aid. The drug is a non-tricyclic antidepressant and differs from most commonly prescribed antidepressants such as SSRIs, as its primary pharmacological action is thought to be norepinephrine-dopamine reuptake inhibition...
, a substituted cathinone with very weak psychostimulant properties relative to most chemicals of this class, is widely used as an atypical antidepressant
Antidepressant
An antidepressant is a psychiatric medication used to alleviate mood disorders, such as major depression and dysthymia and anxiety disorders such as social anxiety disorder. According to Gelder, Mayou &*Geddes people with a depressive illness will experience a therapeutic effect to their mood;...
and smoking cessation
Smoking cessation
Smoking cessation is the process of discontinuing the practice of inhaling a smoked substance. This article focuses exclusively on cessation of tobacco smoking; however, the methods described may apply to cessation of smoking other substances that can be difficult to stop using due to the...
aid, under the brand names Wellbutrin and Zyban, and is also used off-label to treat attention-deficit hyperactive disorder.
According to UN Office on Drugs and Crime
United Nations Office on Drugs and Crime
The United Nations Office on Drugs and Crime is a United Nations agency that was established in 1997 as the Office for Drug Control and Crime Prevention by combining the United Nations International Drug Control Program and the Crime Prevention and Criminal Justice Division in the United Nations...
(UNODC), the world's illegal production in 2007 was 230 to 640 tons of amphetamine-type stimulants (amphetamine, methamphetamine, methcathinone and derivatives) and 72 to 137 tons of methylenedioxyamphetamine (MDA, MDMA, MDEA). The global market for amphetamine-type stimulants is estimated at $65 billion. Production of amphetamines is mainly concentrated near the markets. The trade is mainly concentrated within a country in order to avoid customs control. North America (mainly the states California
California
California is a state located on the West Coast of the United States. It is by far the most populous U.S. state, and the third-largest by land area...
and Oregon
Oregon
Oregon is a state in the Pacific Northwest region of the United States. It is located on the Pacific coast, with Washington to the north, California to the south, Nevada on the southeast and Idaho to the east. The Columbia and Snake rivers delineate much of Oregon's northern and eastern...
) is the leader in the production of methamphetamine, whereas Europe dominates the production of amphetamine and methylenedioxyamphetamine (MDA, MDMA, MDEA).
UNODC
United Nations Office on Drugs and Crime
The United Nations Office on Drugs and Crime is a United Nations agency that was established in 1997 as the Office for Drug Control and Crime Prevention by combining the United Nations International Drug Control Program and the Crime Prevention and Criminal Justice Division in the United Nations...
estimates that between 15 and 50 million people used amphetamines at least once during the year of 2007, that constitutes 0.4–1.2% of the total population aged 15 to 64. In Russia, amphetamines are the third most popular type of drug after marijuana and opiate
Opiate
In medicine, the term opiate describes any of the narcotic opioid alkaloids found as natural products in the opium poppy plant.-Overview:Opiates are so named because they are constituents or derivatives of constituents found in opium, which is processed from the latex sap of the opium poppy,...
s.
Legal status
Because of potential abuse, distribution of amphetamines and their analogues are controlled by the authorities. Those substances are categorized into schedules I-V. Schedule I substances may be used only for scientific or very limited medical purposes with a special license; those substances may not be sold to individuals, even with a prescription. Turnover of substances from Schedule II is allowed under strict control.| Agents | Legal status by 2009. | ||
|---|---|---|---|
| UN Convention on Psychotropic Substances of 1971 | US | Russia | |
| D, L-amphetamine Amphetamine Amphetamine or amfetamine is a psychostimulant drug of the phenethylamine class which produces increased wakefulness and focus in association with decreased fatigue and appetite.Brand names of medications that contain, or metabolize into, amphetamine include Adderall, Dexedrine, Dextrostat,... (racemic) |
Schedule II | Schedule II | Schedule II |
| Dextroamphetamine Dextroamphetamine Dextroamphetamine is a psychostimulant drug which is known to produce increased wakefulness and focus as well as decreased fatigue and decreased appetite.... (D-amphetamine) |
Schedule II | Schedule II | Schedule I |
| Levamphetamine (L-amphetamine) | Schedule II | Schedule II | Schedule III |
| Methamphetamine Methamphetamine Methamphetamine is a psychostimulant of the phenethylamine and amphetamine class of psychoactive drugs... |
Schedule II | Schedule II | Schedule I |
| Cathinone Cathinone Cathinone, or Benzoylethanamine, is a monoamine alkaloid found in the shrub Catha edulis and is chemically similar to ephedrine, cathine and other amphetamines. Cathinone induces the release of dopamine from striatal preparations that are prelabelled either with dopamine or its precursors. It is... Methcathinone Methcathinone Methcathinone , is a psychoactive stimulant, sometimes used as a recreational drug and considered addictive. It is usually snorted, but can be smoked, injected, or taken orally... |
Schedule I | Schedule I | Schedule I |
| MDA 3,4-Methylenedioxyamphetamine 3,4-Methylenedioxyamphetamine , also known as tenamfetamine , is a psychedelic and entactogenic drug of the phenethylamine and amphetamine chemical classes... , MDMA, MDEA Methylenedioxyethylamphetamine 3,4-Methylenedioxy-N-ethylamphetamine is an entactogen, psychedelic, and stimulant of the phenethylamine and amphetamine chemical classes.... |
Schedule I | Schedule I | Schedule I |
| PMA | Schedule I | Schedule I | Schedule I |
| DOB 2,5-Dimethoxy-4-bromoamphetamine DOB, also known as Brolamfetamine and Bromo-DMA, is a psychedelic hallucinogenic drug and a substituted amphetamine of the phenethylamine class of compounds, which can be used as an entheogen. DOB was first synthesized by Alexander Shulgin in 1967... , DOM 2,5-Dimethoxy-4-methylamphetamine 2,5-Dimethoxy-4-methylamphetamine is a psychedelic and a substituted amphetamine... , 3,4,5-TMA Trimethoxyamphetamine TMAs, also known as trimethoxyamphetamines, are a family of isomeric psychedelic hallucinogenic drugs. There exist six different TMAs that differ only in the position of the three methoxy groups: TMA, TMA-2, TMA-3, TMA-4, TMA-5, and TMA-6. The TMAs are analogs of the phenethylamine cactus alkaloid... |
Schedule I | Schedule I | Schedule I |
| Methylphenidate Methylphenidate Methylphenidate is a psychostimulant drug approved for treatment of attention-deficit hyperactivity disorder, postural orthostatic tachycardia syndrome and narcolepsy. It may also be prescribed for off-label use in treatment-resistant cases of lethargy, depression, neural insult and obesity... |
Schedule II | Schedule II | Schedule I |
Chemical derivatives of substituted amphetamine
| Standard Name | Chemical Name | # of Subs |
|---|---|---|
| Amphetamine Amphetamine Amphetamine or amfetamine is a psychostimulant drug of the phenethylamine class which produces increased wakefulness and focus in association with decreased fatigue and appetite.Brand names of medications that contain, or metabolize into, amphetamine include Adderall, Dexedrine, Dextrostat,... |
α-Methyl-2-phenylethylamine | 0 |
| Methamphetamine Methamphetamine Methamphetamine is a psychostimulant of the phenethylamine and amphetamine class of psychoactive drugs... |
N-Methylamphetamine, (1R,2S)- | 1 |
| Ethylamphetamine Ethylamphetamine Ethylamphetamine , also known as etilamfetamine or N-ethylamphetamine, is a stimulant drug of the phenethylamine and amphetamine chemical classes... |
N-Ethylamphetamine | 1 |
| Propylamphetamine Propylamphetamine Propylamphetamine is a psychoactive drug and research chemical of the phenethylamine and amphetamine chemical classes which acts as a stimulant. It was first developed in the 1970s, mainly for research into the metabolism of, and as a comparison tool to other amphetamines... |
N-Propylamphetamine | 1 |
| Isopropylamphetamine Isopropylamphetamine Isopropylamphetamine is a psychostimulant of the phenethylamine and amphetamine chemical classes. It is an isomer of propylamphetamine.- See also :* Amphetamine* Ethylamphetamine* Isoprenaline* Methamphetamine* Propylamphetamine- References :... |
N-iso-Propylamphetamine | 1 |
| Phentermine Phentermine Phentermine, a contraction of "phenyl-tertiary-butylamine", is a psychostimulant drug of the phenethylamine class, chemically related to amphetamine. It is used medically as an appetite suppressant.... |
α-Methylamphetamine | 1 |
| Phenylpropanolamine Phenylpropanolamine Phenylpropanolamine , also known as the stereoisomers norephedrine and norpseudoephedrine, is a psychoactive drug of the phenethylamine and amphetamine chemical classes which is used as a stimulant, decongestant, and anorectic agent. It is commonly used in prescription and over-the-counter cough... (PPA) |
β-Hydroxyamphetamine, (1R,2S)- | 1 |
| Cathine Cathine Cathine, also known as d-norpseudoephedrine, is a psychoactive drug of the phenethylamine and amphetamine chemical classes which acts as a stimulant... |
β-Hydroxyamphetamine, (1S,2S)- | 1 |
| Cathinone Cathinone Cathinone, or Benzoylethanamine, is a monoamine alkaloid found in the shrub Catha edulis and is chemically similar to ephedrine, cathine and other amphetamines. Cathinone induces the release of dopamine from striatal preparations that are prelabelled either with dopamine or its precursors. It is... |
β-Ketoamphetamine | 1 |
| Ortetamine Ortetamine Ortetamine is a stimulant drug of the amphetamine class. In animal drug discrimination tests it substituted for dextroamphetamine more closely than either 3- or 4-methylamphetamine, although with only around 1/10 the potency of dextroamphetamine itself.- See also :* 2-Fluoroamphetamine*... |
2-Methylamphetamine | 1 |
| 2-Fluoroamphetamine 2-Fluoroamphetamine 2-Fluoroamphetamine is a stimulant drug from the amphetamine family which has rarely been sold as a designer drug. In addition, both 2-fluorophenethylamine and amphetamine have been found to act as potent agonists at the trace amine-associated receptor TAAR1, making it likely that... (2-FA) |
2-Fluoroamphetamine | 1 |
| 3-Methylamphetamine 3-Methylamphetamine 3-Methylamphetamine is a stimulant drug from the amphetamine family. It is self-administered by mice to a similar extent to 4-fluoroamphetamine and has comparable properties as a monoamine releaser, although with a more balanced release of all three monoamines, as opposed to the more... (3-MA) |
3-Methylamphetamine | 1 |
| 3-Fluoroamphetamine 3-Fluoroamphetamine 3-Fluoroamphetamine is a stimulant drug from the amphetamine family which acts as a monoamine releaser with similar potency to methamphetamine but more selectivity for dopamine and noradrenaline release over serotonin... (3-FA) |
3-Fluoroamphetamine | 1 |
| Norfenfluramine Norfenfluramine Norfenfluramine is a psychoactive drug which functions as a serotonin releasing agent and potent 5HT2B receptor agonist. The action of norfenfluramine on 5HT2B receptors on heart valves leads to a characteristic pattern of heart failure following proliferation of cardiac fibroblasts on the... |
3-Trifluoromethylamphetamine | 1 |
| 4-Methylamphetamine 4-Methylamphetamine 4-Methylamphetamine is a stimulant and anorectic drug of the phenethylamine and amphetamine chemical classes.... (4-MA) |
4-Methylamphetamine | 1 |
| para-Methoxyamphetamine (PMA) | 4-Methoxyamphetamine | 1 |
| para-Ethoxyamphetamine Para-Ethoxyamphetamine para-Ethoxyamphetamine, also known as 4-ethoxyamphetamine , is a psychoactive drug and research chemical of the phenethylamine and amphetamine chemical classes which is closely related to the infamous para-methoxyamphetamine . para-Ethoxyamphetamine has similar effects to PMA in animal studies,... |
4-Ethoxyamphetamine | 1 |
| 4-Methylthioamphetamine (4-MTA) | 4-Methylthioamphetamine | 1 |
| Norpholedrine (α-Me-TRA) | 4-Hydroxyamphetamine | 1 |
| para-Bromoamphetamine Para-Bromoamphetamine para-Bromoamphetamine , also known as 4-bromoamphetamine , is an amphetamine derivative which acts as a serotonin-norepinephrine-dopamine releasing agent and produces stimulant effects... (PBA, 4-BA) |
4-Bromoamphetamine | 1 |
| para-Chloroamphetamine Para-Chloroamphetamine para-Chloroamphetamine , also known as 4-chloroamphetamine , is an amphetamine derivative and monoamine releaser similar to MDMA, but with substantially higher neurotoxicity, thought to be due to the unrestrained release of both serotonin and dopamine as with MDMA itself... (PCA, 4-CA) |
4-Chloroamphetamine | 1 |
| para-Fluoroamphetamine (PFA, 4-FA, 4-FMP) | 4-Fluoroamphetamine | 1 |
| para-Iodoamphetamine Para-Iodoamphetamine para-Iodoamphetamine , also known as 4-iodoamphetamine , is a research chemical of the phenethylamine and amphetamine chemical classes.It acts as a selective serotonin releasing agent and is also a MAOI.... (PIA, 4-IA) |
4-Iodoamphetamine | 1 |
| Dimethylamphetamine Dimethylamphetamine Dimethylamphetamine , also referred to as dimetamfetamine and N,N-dimethylamphetamine, is a stimulant drug of the phenethylamine and amphetamine chemical classes. Dimethylamphetamine has weaker stimulant effects than amphetamine or methamphetamine and is considerably less addictive and less... |
N,N-Dimethylamphetamine | 2 |
| Benzphetamine Benzphetamine Benzphetamine is an anorectic drug marketed under this brand in the USA by Pharmacia. Benzphetamine is used as a short term adjunct in management of exogenous obesity. It is closely related to amphetamine.- Pharmacology :... |
N-Benzyl-N-methylamphetamine | 2 |
| Selegiline Selegiline Selegiline is a drug used for the treatment of early-stage Parkinson's disease, depression and senile dementia. In normal clinical doses it is a selective irreversible MAO-B inhibitor, however in larger doses it loses its specificity and also inhibits MAO-A... |
N-Methyl-N-propargylamphetamine, (R)- | 2 |
| Mephentermine Mephentermine Mephentermine is a cardiac stimulant. It was formerly used in Wyamine nasal decongestant inhalers and before that as a stimulant in psychiatry.It has been used as a treatment for hypotension.-References:... |
N-Methyl-α-methylamphetamine | 2 |
| Phenpentermine Phenpentermine Pentorex , also known as phenpentermine or α,β-dimethylamphetamine, is a stimulant drug related to phentermine which is used as an anorectic to assist with weight loss. It also acts as a diuretic. Pentorex was developed by Nordmark in the 1960s.... |
α,β-Dimethylamphetamine | 2 |
| Ephedrine Ephedrine Ephedrine is a sympathomimetic amine commonly used as a stimulant, appetite suppressant, concentration aid, decongestant, and to treat hypotension associated with anaesthesia.... (EPH) |
β-Hydroxy-N-methylamphetamine, (1R,2S)- | 2 |
| Pseudoephedrine Pseudoephedrine Pseudoephedrine is a sympathomimetic drug of the phenethylamine and amphetamine chemical classes. It is used as a nasal/sinus decongestant and stimulant, or as a wakefulness-promoting agent.... (PSE) |
β-Hydroxy-N-methylamphetamine, (1S,2S)- | 2 |
| Methcathinone Methcathinone Methcathinone , is a psychoactive stimulant, sometimes used as a recreational drug and considered addictive. It is usually snorted, but can be smoked, injected, or taken orally... |
β-Keto-N-methylamphetamine | 2 |
| Ethcathinone Ethcathinone Ethcathinone, also known as ethylpropion, is a stimulant drug of the phenethylamine, amphetamine, and cathinone chemical classes. It is an active metabolite of the prodrug diethylcathinone and is fully responsible for its effects... |
β-Keto-N-ethylamphetamine | 2 |
| Clortermine Clortermine Clortermine was developed by Ciba in the 1960s and is an anorectic drug of the amphetamine class. It is the 2-chloro analogue of the better known appetite suppressant phentermine, and is the 2-chloro positional isomer of chlorphentermine... |
2-Chloro-α-methylamphetamine | 2 |
| Methoxymethylamphetamine (MMA) | 3-Methoxy-4-methylamphetamine | 2 |
| Fenfluramine Fenfluramine Fenfluramine is a drug that was part of the Fen-Phen anti-obesity medication . Fenfluramine was introduced on the U.S. market in 1973. It is the racemic mixture of two enantiomers, dextrofenfluramine and levofenfluramine... |
3-Trifluoromethyl-N-ethylamphetamine | 2 |
| Dexfenfluramine Dexfenfluramine Dexfenfluramine, marketed as dexfenfluramine hydrochloride under the name Redux, is a serotoninergic anorectic drug: it reduces appetite by increasing the amount of extracellular serotonin in the brain... |
3-Trifluoromethyl-N-ethylamphetamine, (S)- | 2 |
| 4-Methylmethamphetamine 4-Methylmethamphetamine 4-Methylmethamphetamine is a putative stimulant and entactogen drug of the amphetamine class. It is the β-deketo analogue of mephedrone.- See also :* 4-Methylamphetamine * 4-Methylmethcathinone * 3-Methoxymethamphetamine... (4-MMA) |
4-Methyl-N-methylamphetamine | 2 |
| Para-methoxymethamphetamine (PMMA) | 4-Methoxy-N-methylamphetamine | 2 |
| para-Methoxyethylamphetamine (PMEA) | 4-Methoxy-N-ethylamphetamine | 2 |
| Pholedrine Pholedrine Pholedrine , also known as 4-hydroxy-N-methylamphetamine and para-hydroxymethamphetamine, is a drug that stimulates the sympathetic nervous system. It is administered as a topical eye drop form for the purpose of dilating the pupil and can be used to diagnose Horner's syndrome.- References :... |
4-Hydroxy-N-methylamphetamine | 2 |
| Chlorphentermine Chlorphentermine Chlorphentermine is an appetite suppressant of the phenethylamine class. Developed in 1962, it is the 4-chloro derivative of the better known appetite suppressant phentermine, which is still in current use.Chlorphentermine itself is a relatively weak stimulant with little abuse potential, but is... |
4-Chloro-α-methylamphetamine | 2 |
| para-Fluoromethamphetamine (PFMA, 4-FMA) | 4-Fluoro-N-methylamphetamine | 2 |
| Xylopropamine | 3,4-Dimethylamphetamine | 2 |
| α-Methyldopamine (α-Me-DA) | 3,4-Dihydroxyamphetamine | 2 |
| Methylenedioxyamphetamine (MDA) | 3,4-Methylenedioxyamphetamine | 2 |
| Dimethoxyamphetamine Dimethoxyamphetamine DMA, or dimethoxyamphetamine, is a series of lesser-known psychedelic drugs similar in structure to amphetamine and to trimethoxyamphetamine . They were first synthesized by Alexander Shulgin and written up in his book PiHKAL ... (DMA) |
X,X-Dimethoxyamphetamine | 2 |
| Nordefrin (α-Me-NE) | β,3,4-Trihydroxyamphetamine, (R)- | 3 |
| Oxilofrine Oxilofrine Oxilofrine ' is a stimulant drug of the amphetamine chemical class.... |
β,4-Dihydroxy-N-methylamphetamine | 3 |
| Aleph Aleph (psychedelic) Aleph, or 2,5-dimethoxy-4-methylthioamphetamine, is a psychedelic hallucinogenic drug and a substituted amphetamine of the phenethylamine class of compounds, which can be used as an entheogen. It was first synthesized by Alexander Shulgin. In his book PiHKAL , Shulgin lists the dosage range as... |
2,5-dimethoxy-4-methylthioamphetamine | 3 |
| Dimethoxybromoamphetamine (DOB) | 2,5-Dimethoxy-4-bromoamphetamine | 3 |
| Dimethoxychloroamphetamine (DOC) | 2,5-Dimethoxy-4-chloroamphetamine | 3 |
| Dimethoxyfluoroethylamphetamine (DOEF) | 2,5-Dimethoxy-4-fluoroethylamphetamine | 3 |
| Dimethoxyethylamphetamine (DOET) | 2,5-Dimethoxy-4-ethylamphetamine | 3 |
| Dimethoxyfluoroamphetamine (DOF) | 2,5-Dimethoxy-4-fluoroamphetamine | 3 |
| Dimethoxyiodoamphetamine (DOI) | 2,5-Dimethoxy-4-iodoamphetamine | 3 |
| Dimethoxymethylamphetamine (DOM) | 2,5-Dimethoxy-4-methylamphetamine | 3 |
| Dimethoxynitroamphetamine (DON) | 2,5-Dimethoxy-4-nitroamphetamine | 3 |
| Dimethoxypropylamphetamine (DOPR) | 2,5-Dimethoxy-4-propylamphetamine | 3 |
| Dimethoxytrifluoromethylamphetamine (DOTFM) | 2,5-Dimethoxy-4-trifluoromethylamphetamine | 3 |
| Methylenedioxymethamphetamine (MDMA) | 3,4-Methylenedioxy-N-methylamphetamine | 3 |
| Methylenedioxyethylamphetamine Methylenedioxyethylamphetamine 3,4-Methylenedioxy-N-ethylamphetamine is an entactogen, psychedelic, and stimulant of the phenethylamine and amphetamine chemical classes.... (MDEA) |
3,4-Methylenedioxy-N-ethylamphetamine | 3 |
| Methylenedioxyhydroxyamphetamine (MDOH) | 3,4-Methylenedioxy-N-hydroxyamphetamine | 3 |
| 2-Methyl-MDA 2-Methyl-MDA 2-Methyl-3,4-methylenedioxyamphetamine is an entactogen and psychedelic drug of the amphetamine class. It acts as a selective serotonin releasing agent , with IC50 values of 93nM, 12,000nM, and 1,937nM for serotonin, dopamine, and norepinephrine efflux. 2-Methyl-MDA is more potent than MDA,... |
3,4-Methylenedioxy-2-methylamphetamine | 3 |
| 5-Methyl-MDA | 4,5-Methylenedioxy-3-methylamphetamine | 3 |
| Methoxymethylenedioxyamphetamine (MMDA) | 3-Methoxy-4,5-methylenedioxyamphetamine | 3 |
| Trimethoxyamphetamine Trimethoxyamphetamine TMAs, also known as trimethoxyamphetamines, are a family of isomeric psychedelic hallucinogenic drugs. There exist six different TMAs that differ only in the position of the three methoxy groups: TMA, TMA-2, TMA-3, TMA-4, TMA-5, and TMA-6. The TMAs are analogs of the phenethylamine cactus alkaloid... (TMA) |
X,X,X-Trimethoxyamphetamine | 3 |
| Dimethylcathinone Dimethylcathinone Metamfepramone is a stimulant drug of the phenethylamine, and cathinone chemical classes... |
β-Keto-N,N-dimethylamphetamine | 3 |
| Diethylcathinone Diethylcathinone Amfepramone , is a stimulant drug of the phenethylamine, amphetamine, and cathinone chemical classes that is used as an appetite suppressant.- Pharmacology :Amfepramone itself lacks any affinity for the... |
β-Keto-N,N-diethylamphetamine | 3 |
| Bupropion Bupropion Bupropion is an atypical antidepressant and smoking cessation aid. The drug is a non-tricyclic antidepressant and differs from most commonly prescribed antidepressants such as SSRIs, as its primary pharmacological action is thought to be norepinephrine-dopamine reuptake inhibition... |
β-Keto-3-chloro-N-tert-butylamphetamine | 3 |
| Mephedrone (4-MMC) | β-Keto-4-methyl-N-methylamphetamine | 3 |
| Methedrone (PMMC) | β-Keto-4-methoxy-N-methylamphetamine | 3 |
| Brephedrone (4-BMC) | β-Keto-4-bromo-N-methylamphetamine | 3 |
| Flephedrone Flephedrone Flephedrone, also known as 4-fluoromethcathinone , is a stimulant drug of the cathinone chemical class.- History :Flephedrone started to be sold as a designer drug in 2008, along with its structural isomer 3-fluoromethcathinone .- Toxicity :Flephedrone has only a short history of human use and its... (4-FMC) |
β-Keto-4-fluoro-N-methylamphetamine | 3 |
| Ganesha Ganesha (psychedelic) Ganesha, or 2,5-dimethoxy-3,4-dimethylamphetamine, is a lesser-known psychedelic drug. It is also a substituted amphetamine. It was first synthesized by Alexander Shulgin. In his book PiHKAL , the dosage range is listed as 24–32 mg. Ganesha is sold in the form of dark red crystals... |
2,5-Dimethoxy-3,4-dimethylamphetamine | 4 |
| Dimethoxymethylenedioxyamphetamine (DMMDA) | 2,5-Dimethoxy-3,4-methylenedioxyamphetamine | 4 |
| FLEA FLEA (psychedelic) 3,4-Methylenedioxy-N-hydroxy-N-methylamphetamine is an entactogen, psychedelic, and stimulant of the phenethylamine and amphetamine chemical classes. It is the N-hydroxy homologue of MDMA , and the N-methyl homologue of MDOH. MDHMA was first synthesized and assayed by Alexander Shulgin... (MDMHA) |
3,4-Methylenedioxy-N-methyl-N-hydroxyamphetamine | 4 |
| Methoxymethylenedioxymethamphetamine (MMDMA) | 3-Methoxy-4,5-methylenedioxy-N-methylamphetamine | 4 |
| EDMA EDMA 3,4-Ethylenedioxy-N-methylamphetamine is an entactogen drug of the amphetamine class. It is an analogue of MDMA where the methylenedioxy ring has been replaced by an ethylenedioxy ring. EDMA was first synthesized by Alexander Shulgin. In his book PiHKAL, the dosage is listed as 150–250 mg,... (MDMC) |
3,4-Ethylenedioxy-N-methylamphetamine | 4 |
| Ethylone (MDEC, bk-MDEA) | β-Keto-3,4-methylenedioxy-N-ethylamphetamine | 4 |