Sympathomimetic amine
Encyclopedia
Sympathomimetic drugs mimic the effects of transmitter substances of the sympathetic nervous system
such as catecholamines, epinephrine
(adrenaline), norepinephrine
(noradrenaline), dopamine
, etc. Such drugs are used to treat cardiac arrest
and low blood pressure
, or even delay premature labor, among other things.
These drugs act at the postganglionic sympathetic terminal, either directly activating postsynaptic receptors
, blocking breakdown and reuptake
, or stimulating production and release of catecholamines.
s, release stimulants, and reuptake inhibitors.
s can produce sympathomimetic effects. Salbutamol
is a very commonly used direct-acting β2-agonist
. Other examples include phenylephrine
, isoproterenol
, and dobutamine
.
is used intravenously to treat hypertensive crisis.
, and cocaine
, which act by blocking and reversing norepinephrine transporter
(NET) activity. NET is a transport protein expressed on the surface of some cells that clears noradrenaline and adrenaline from the extracellular space and into cells
, terminating the signaling effects.
(MAO), thus the monoamine oxidase inhibitor
(MAOI) drugs can induce such effects. COMT inhibitor
s can also decrease metabolism of norepinephrine and epinephrine.
1- Substitution on aromatic ring-
The presence of hydroxy group in the benzene ring at 3rd and 4th position shows maximum alpha and beta activity
also affect dopamine
, and some substances like MDMA affect serotonin
.
Norepinephrine is synthesized by the body into epinephrine, causing central nervous system
stimulation. Thus, all sympathomimetic amines fall into the larger group of stimulant
s (see psychoactive drug
chart). Many of these stimulants have therepeutic use and abuse potential
, can induce tolerance, and possibly physical dependence
.
" and "sympathomimetic" are similar, but not identical. For example, both cause mydriasis
, but parasympatholytics reduce accommodation
(cycloplegia
) while sympathomimetics do not.
Sympathetic nervous system
The sympathetic nervous system is one of the three parts of the autonomic nervous system, along with the enteric and parasympathetic systems. Its general action is to mobilize the body's nervous system fight-or-flight response...
such as catecholamines, epinephrine
Epinephrine
Epinephrine is a hormone and a neurotransmitter. It increases heart rate, constricts blood vessels, dilates air passages and participates in the fight-or-flight response of the sympathetic nervous system. In chemical terms, adrenaline is one of a group of monoamines called the catecholamines...
(adrenaline), norepinephrine
Norepinephrine
Norepinephrine is the US name for noradrenaline , a catecholamine with multiple roles including as a hormone and a neurotransmitter...
(noradrenaline), 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...
, etc. Such drugs are used to treat cardiac arrest
Cardiac arrest
Cardiac arrest, is the cessation of normal circulation of the blood due to failure of the heart to contract effectively...
and low 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...
, or even delay premature labor, among other things.
These drugs act at the postganglionic sympathetic terminal, either directly activating postsynaptic receptors
Receptor (biochemistry)
In biochemistry, a receptor is a molecule found on the surface of a cell, which receives specific chemical signals from neighbouring cells or the wider environment within an organism...
, blocking breakdown and reuptake
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....
, or stimulating production and release of catecholamines.
Mechanisms of action
The mechanisms of sympathomimetic drugs can be direct-acting, such as α-adrenergic agonists, β-adrenergic agonists, and dopaminergic agonists; or indirect-acting, such as MAOIs, COMT inhibitorCOMT inhibitor
A COMT inhibitor is a drug that inhibits the action of catechol-O-methyl transferase. This enzyme is involved in degrading neurotransmitters. COMT inhibitors are used in the treatment of Parkinson's disease....
s, release stimulants, and reuptake inhibitors.
Adrenergic receptor agonists
Direct stimulation of the α- and β-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 can produce sympathomimetic effects. Salbutamol
Salbutamol
Salbutamol or albuterol is a short-acting β2-adrenergic receptor agonist used for the relief of bronchospasm in conditions such as asthma and chronic obstructive pulmonary disease. It is marketed as Ventolin among other brand names....
is a very commonly used direct-acting β2-agonist
Beta2-adrenergic receptor agonist
β2-adrenergic agonists, also known as β2-adrenergic receptor agonists, are a class of drugs used to treat asthma and other pulmonary disease states.-Uses:...
. Other examples include phenylephrine
Phenylephrine
Phenylephrine is a selective α1-adrenergic receptor agonist used primarily as a decongestant, as an agent to dilate the pupil, and to increase blood pressure...
, isoproterenol
Isoproterenol
Isoprenaline or isoproterenol is a medication used for the treatment of bradycardia , heart block, and rarely for asthma...
, and dobutamine
Dobutamine
Dobutamine is a sympathomimetic drug used in the treatment of heart failure and cardiogenic shock. Its primary mechanism is direct stimulation of β1 receptors of the sympathetic nervous system. Dobutamine was developed by a laboratory led by Drs...
.
Dopaminergic agonists
Stimulation of the D1 receptor by dopaminergic agonists such as fenoldopamFenoldopam
Fenoldopam is a drug and synthetic benzazepine derivative which acts as a peripheral selective D1 receptor weak partial agonist/antagonist and is used as an antihypertensive. It was approved by the Food and Drug Administration in September 1997...
is used intravenously to treat hypertensive crisis.
Norepinephrine transporter blockade
Classical sympathomimetic drugs are amphetamines (including MDMA), ephedrineEphedrine
Ephedrine is a sympathomimetic amine commonly used as a stimulant, appetite suppressant, concentration aid, decongestant, and to treat hypotension associated with anaesthesia....
, and 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...
, which act by blocking and reversing norepinephrine transporter
Norepinephrine transporter
The norepinephrine transporter , also known as solute carrier family 6 member 2 , is a protein that in humans is encoded by the SLC6A2 gene....
(NET) activity. NET is a transport protein expressed on the surface of some cells that clears noradrenaline and adrenaline from the extracellular space and into cells
Cell (biology)
The cell is the basic structural and functional unit of all known living organisms. It is the smallest unit of life that is classified as a living thing, and is often called the building block of life. The Alberts text discusses how the "cellular building blocks" move to shape developing embryos....
, terminating the signaling effects.
Inhibition of epinephrine and norepinephrine metabolism
Inhibition of norepinephrine or epinephrine metabolism can produce sympathomimetic effects. Both are metabolized mainly by the enzyme monoamine oxidaseMonoamine oxidase
L-Monoamine oxidases are a family of enzymes that catalyze the oxidation of monoamines. They are found bound to the outer membrane of mitochondria in most cell types in the body. The enzyme was originally discovered by Mary Bernheim in the liver and was named tyramine oxidase...
(MAO), thus the monoamine oxidase inhibitor
Monoamine oxidase inhibitor
Monoamine oxidase inhibitors are a class of antidepressant drugs prescribed for the treatment of depression. They are particularly effective in treating atypical depression....
(MAOI) drugs can induce such effects. COMT inhibitor
COMT inhibitor
A COMT inhibitor is a drug that inhibits the action of catechol-O-methyl transferase. This enzyme is involved in degrading neurotransmitters. COMT inhibitors are used in the treatment of Parkinson's disease....
s can also decrease metabolism of norepinephrine and epinephrine.
Structure Activity Relationship
A primary or secondary aliphatic amine separated by 2 carbons from a substituted benzene ring is minimally required for high agonist activity. The pKa of the amine is approximately 8.5-10.1- Substitution on aromatic ring-
The presence of hydroxy group in the benzene ring at 3rd and 4th position shows maximum alpha and beta activity
Cross-reactivity
Substances like cocaineCocaine
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...
also affect 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...
, and some substances like MDMA affect 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...
.
Norepinephrine is synthesized by the body into epinephrine, causing 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...
stimulation. Thus, all sympathomimetic amines fall into the larger group of stimulant
Stimulant
Stimulants are psychoactive drugs which induce temporary improvements in either mental or physical function or both. Examples of these kinds of effects may include enhanced alertness, wakefulness, and locomotion, among others...
s (see psychoactive drug
Psychoactive drug
A psychoactive drug, psychopharmaceutical, or psychotropic is a chemical substance that crosses the blood–brain barrier and acts primarily upon the central nervous system where it affects brain function, resulting in changes in perception, mood, consciousness, cognition, and behavior...
chart). Many of these stimulants have therepeutic use and abuse potential
Drug abuse
Substance abuse, also known as drug abuse, refers to a maladaptive pattern of use of a substance that is not considered dependent. The term "drug abuse" does not exclude dependency, but is otherwise used in a similar manner in nonmedical contexts...
, can induce tolerance, and possibly physical dependence
Physical dependence
Physical dependence refers to a state resulting from chronic use of a drug that has produced tolerance and where negative physical symptoms of withdrawal result from abrupt discontinuation or dosage reduction...
.
Comparison
"ParasympatholyticParasympatholytic
A parasympatholytic agent is a substance or activity that reduces the activity of the parasympathetic nervous system. A parasympatholytic agent is a substance or activity that reduces the activity of the parasympathetic nervous system. A parasympatholytic agent is a substance or activity that...
" and "sympathomimetic" are similar, but not identical. For example, both cause 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...
, but parasympatholytics reduce accommodation
Accommodation (eye)
Accommodation is the process by which the vertebrate eye changes optical power to maintain a clear image on an object as its distance changes....
(cycloplegia
Cycloplegia
Cycloplegia is paralysis of the ciliary muscle of the eye, resulting in a loss of accommodation.-Anatomy:The iris is the heavily pigmented colored part of the eye. It has a contractile diaphragm in front of the lens with a central opening called the pupil...
) while sympathomimetics do not.
Examples
- ephedrineEphedrineEphedrine is a sympathomimetic amine commonly used as a stimulant, appetite suppressant, concentration aid, decongestant, and to treat hypotension associated with anaesthesia....
(found in EphedraEphedraEphedra 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...
) - pseudoephedrinePseudoephedrinePseudoephedrine 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....
(also found in Ephedra species) - amphetamineAmphetamineAmphetamine 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,...
- methamphetamineMethamphetamineMethamphetamine is a psychostimulant of the phenethylamine and amphetamine class of psychoactive drugs...
- 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...
(Ritalin) - lisdexamfetamine (Vyvanse)
- cocaineCocaineCocaine 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...
(found in Erythroxylum coca, Coca) - cathinoneCathinoneCathinone, 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...
(found in Catha edulis, Khat) - cathineCathineCathine, also known as d-norpseudoephedrine, is a psychoactive drug of the phenethylamine and amphetamine chemical classes which acts as a stimulant...
(also found in Catha edulis) - methcathinoneMethcathinoneMethcathinone , 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...
- benzylpiperazineBenzylpiperazineBenzylpiperazine is a recreational drug with euphoric, stimulant properties. The effects produced by BZP are comparable to those produced by amphetamine. Adverse effects have been reported following its use including acute psychosis, renal toxicity, and seizures...
(BZP) - methylenedioxypyrovalerone (MDPV)
- 4-methylaminorex
- pemolinePemolinePemoline was first synthesized in 1913 but it's activity was not discovered until the 1930s. Under the names it was used as a medication used to treat attention-deficit hyperactivity disorder and narcolepsy. Under the Convention on Psychotropic Substances, it is a Schedule IV drug...
(Cylert) - phenmetrazinePhenmetrazinePhenmetrazine is a stimulant drug of the morpholine chemical class that was previously used as an appetite suppressant, but has since been withdrawn from the market...
(Preludin) - propylhexedrinePropylhexedrinePropylhexedrine is a stimulant drug related to methamphetamine. It is used mainly to provide temporary symptomatic relief of nasal congestion due to colds, allergies and allergic rhinitis...
(Benzedrex)