Ethylphenidate
Encyclopedia
Ethylphenidate is a potent psychostimulant
that acts as both a dopamine reuptake inhibitor
and norepinephrine reuptake inhibitor
, meaning it effectively boosts the levels of the norepinephrine
and dopamine
neurotransmitter
s in the brain, by binding to, and partially blocking the transporter protein
s that normally remove those monoamines from the synaptic cleft.
It is most commonly formed when ethanol
and methylphenidate
are coingested, via hepatic
transesterification
. Ethylphenidate formation appears to be more common when large quantities of methylphenidate and alcohol are consumed at the same time, such as in non-medical use or overdose scenarios. This carboxylesterase
-dependent transesterification process is also known to occur when cocaine
and alcohol are consumed together, forming cocaethylene
.
Ethylphenidate is more selective to the dopamine transporter
(DAT) than methylphenidate, having approximately the same efficacy as the parent compound, but has significantly less activity on the norepinephrine transporter
(NET). It has a near-identical dopaminergic pharmacodynamic
profile as methylphenidate, which is primarily responsible for its euphoric
and reinforcing effects.
Interestingly, the eudysmic ratio
for ethylphenidate is superior to that seen for TMP.
TEP is less stimulatory than TMP at 5mg/kg, although both compounds generalize at 10mg/kg. This is suggestive of a noradrenergic stimulatory effect present for TMP at lower doses.
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...
that acts as both a dopamine reuptake inhibitor
Dopamine reuptake inhibitor
A dopamine reuptake inhibitor is a type of drug that acts as a reuptake inhibitor for the neurotransmitter dopamine by blocking the action of the dopamine transporter...
and norepinephrine reuptake inhibitor
Norepinephrine reuptake inhibitor
A norepinephrine reuptake inhibitor or adrenergic reuptake inhibitor , is a type of drug which acts as a reuptake inhibitor for the neurotransmitters norepinephrine and epinephrine by blocking the action of the norepinephrine transporter...
, meaning it effectively boosts the levels of the norepinephrine
Norepinephrine
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...
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...
s in the brain, by binding to, and partially blocking the transporter protein
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
s that normally remove those monoamines from the synaptic cleft.
It is most commonly formed when ethanol
Alcoholic beverage
An alcoholic beverage is a drink containing ethanol, commonly known as alcohol. Alcoholic beverages are divided into three general classes: beers, wines, and spirits. They are legally consumed in most countries, and over 100 countries have laws regulating their production, sale, and consumption...
and 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...
are coingested, via hepatic
Liver
The liver is a vital organ present in vertebrates and some other animals. It has a wide range of functions, including detoxification, protein synthesis, and production of biochemicals necessary for digestion...
transesterification
Transesterification
In organic chemistry, transesterification is the process of exchanging the organic group R″ of an ester with the organic group R′ of an alcohol. These reactions are often catalyzed by the addition of an acid or base catalyst...
. Ethylphenidate formation appears to be more common when large quantities of methylphenidate and alcohol are consumed at the same time, such as in non-medical use or overdose scenarios. This carboxylesterase
Carboxylesterase
In enzymology, a carboxylesterase is an enzyme that catalyzes the chemical reactionThus, the two substrates of this enzyme are carboxylic ester and H2O, whereas its two products are alcohol and carboxylate....
-dependent transesterification process is also known to occur when 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...
and alcohol are consumed together, forming cocaethylene
Cocaethylene
Cocaethylene is the ethyl ester of benzoylecgonine. It is structurally similar to cocaine, which is the methyl ester of benzoylecgonine. Cocaethylene is formed in vivo when cocaine and ethyl alcohol have been ingested simultaneously....
.
Ethylphenidate is more selective to the dopamine transporter
Dopamine transporter
The dopamine transporter is a membrane-spanning protein that pumps the neurotransmitter dopamine out of the synapse back into cytosol, from which other transporters sequester DA and NE into vesicles for later storage and release...
(DAT) than methylphenidate, having approximately the same efficacy as the parent compound, but has significantly less activity on the 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). It has a near-identical dopaminergic pharmacodynamic
Pharmacodynamics
Pharmacodynamics is the study of the biochemical and physiological effects of drugs on the body or on microorganisms or parasites within or on the body and the mechanisms of drug action and the relationship between drug concentration and effect...
profile as methylphenidate, which is primarily responsible for its euphoric
Euphoria
Euphoria is an emotional and mental state defined as a sense of great elation and well being.Euphoria may also refer to:* Euphoria , a genus of scarab beetles* Euphoria, a genus name previously used for the longan and other trees...
and reinforcing effects.
Interestingly, the eudysmic ratio
Eudysmic ratio
The Eudysmic ratio is a common term in pharmacology, chemistry, and molecular biology. The eudysmic ratio describes the difference in pharmacologic activity between the two enantiomers of a drug....
for ethylphenidate is superior to that seen for TMP.
| Compound | Binding DAT | Binding NET | Uptake DA | Uptake NE |
|---|---|---|---|---|
| d-TMP | 139 | 408 | 28 | 46 |
| d-TEP | 276 | 2479 | 24 | 247 |
| dl-TMP | 105 | 1560 | 24 | 31 |
| dl-TEP | 382 | 4824 | 82 | 408 |
TEP is less stimulatory than TMP at 5mg/kg, although both compounds generalize at 10mg/kg. This is suggestive of a noradrenergic stimulatory effect present for TMP at lower doses.
See also
- CocaethyleneCocaethyleneCocaethylene is the ethyl ester of benzoylecgonine. It is structurally similar to cocaine, which is the methyl ester of benzoylecgonine. Cocaethylene is formed in vivo when cocaine and ethyl alcohol have been ingested simultaneously....
(compound formed when 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...
and ethanolEthanolEthanol, also called ethyl alcohol, pure alcohol, grain alcohol, or drinking alcohol, is a volatile, flammable, colorless liquid. It is a psychoactive drug and one of the oldest recreational drugs. Best known as the type of alcohol found in alcoholic beverages, it is also used in thermometers, as a...
are taken together) - 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...
- Ethanol (drinking alcohol)EthanolEthanol, also called ethyl alcohol, pure alcohol, grain alcohol, or drinking alcohol, is a volatile, flammable, colorless liquid. It is a psychoactive drug and one of the oldest recreational drugs. Best known as the type of alcohol found in alcoholic beverages, it is also used in thermometers, as a...