Ethylphenidate (EPH), also known as Baxtercaine in the

United Kingdom The United Kingdom of Great Britain and Northern Ireland, commonly known as the United Kingdom (UK) or Britain, is a country in Europe, off the north-western coast of the continental mainland. It comprises England, Scotland, Wales and North ...

is a psychostimulant and a close

analog Analog or analogue may refer to: Computing and electronics * Analog signal, in which information is encoded in a continuous variable ** Analog device, an apparatus that operates on analog signals *** Analog electronics, circuits which use analog ...

methylphenidate Methylphenidate, sold under the brand names Ritalin and Concerta among others, is the most widely prescribed central nervous system (CNS) stimulant medication used to treat attention deficit hyperactivity disorder (ADHD) and, to a lesser extent, ...

. Ethylphenidate acts as both a

dopamine reuptake inhibitor A dopamine reuptake inhibitor (DRI) is a class of drug which acts as a reuptake inhibitor of the monoamine neurotransmitter dopamine by blocking the action of the dopamine transporter (DAT). Reuptake inhibition is achieved when extracellular dopa ...

and

norepinephrine reuptake inhibitor A norepinephrine reuptake inhibitor (NRI, NERI) or noradrenaline reuptake inhibitor or adrenergic reuptake inhibitor (ARI), is a type of drug that acts as a reuptake inhibitor for the neurotransmitters norepinephrine (noradrenaline) and epineph ...

, meaning it effectively boosts the levels of the

norepinephrine Norepinephrine (NE), also called noradrenaline (NA) or noradrenalin, is an organic chemical in the catecholamine family that functions in the brain and body as both a hormone and neurotransmitter. The name "noradrenaline" (from Latin '' ad'', ...

and

dopamine Dopamine (DA, a contraction of 3,4-dihydroxyphenethylamine) is a neuromodulatory molecule that plays several important roles in cells. It is an organic compound, organic chemical of the catecholamine and phenethylamine families. Dopamine const ...

neurotransmitter A neurotransmitter is a signaling molecule secreted by a neuron to affect another cell across a synapse. The cell receiving the signal, any main body part or target cell, may be another neuron, but could also be a gland or muscle cell. Neuro ...

s in the brain, by binding to, and partially blocking the transporter

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...

s that normally remove those

monoamine Monoamine neurotransmitters are neurotransmitters and neuromodulators that contain one amino group connected to an aromatic ring by a two-carbon chain (such as -CH2-CH2-). Examples are dopamine, norepinephrine and serotonin. All monoamines are ...

s from the

synaptic cleft Chemical synapses are biological junctions through which neurons' signals can be sent to each other and to non-neuronal cells such as those in muscles or glands. Chemical synapses allow neurons to form circuits within the central nervous syste ...

. However, considering the close similarities between ethylphenidate and methylphenidate and the fact that methylphenidate, like

cocaine Cocaine (from , from , ultimately from Quechuan languages, Quechua: ''kúka'') is a central nervous system (CNS) stimulant mainly recreational drug use, used recreationally for its euphoria, euphoric effects. It is primarily obtained from t ...

, actually does not primarily act as a "classical" reuptake inhibitor, but rather as an "

inverse agonist In pharmacology, an inverse agonist is a drug that binds to the same receptor as an agonist but induces a pharmacological response opposite to that of the agonist. A neutral antagonist has no activity in the absence of an agonist or inverse agon ...

at the DAT" (also called a "

negative allosteric modulator In pharmacology and biochemistry, allosteric modulators are a group of substances that bind to a receptor to change that receptor's response to stimulus. Some of them, like benzodiazepines, are drugs. The site that an allosteric modulator binds t ...

at the DAT"), it is at least very likely that ethylphenidate also primarily acts as an inverse DAT agonist instead of (or at least only secondarily) as a classical reuptake inhibitor (which could be called a "

competitive antagonist A receptor antagonist is a type of receptor ligand or drug that blocks or dampens a biological response by binding to and blocking a receptor rather than activating it like an agonist. Antagonist drugs interfere in the natural operation of recep ...

at the DAT" using a similar terminology as "negative allosteric modulator at the DAT", which per definition means that its mechanism is non-competitive).

Pharmacokinetics

Ethylphenidate metabolizes into methylphenidate and

ritalinic acid Ritalinic acid is a substituted phenethylamine and an inactive major metabolite of the stimulant, psychostimulant drugs methylphenidate and ethylphenidate. When administered orally, methylphenidate is extensively metabolized in the liver by hydro ...

. Tiny amounts of ethylphenidate can be formed ''

in vivo Studies that are ''in vivo'' (Latin for "within the living"; often not italicized in English) are those in which the effects of various biological entities are tested on whole, living organisms or cells, usually animals, including humans, and ...

'' when a

solvent A solvent (s) (from the Latin '' solvō'', "loosen, untie, solve") is a substance that dissolves a solute, resulting in a solution. A solvent is usually a liquid but can also be a solid, a gas, or a supercritical fluid. Water is a solvent for ...

(specifically

ethanol Ethanol (abbr. EtOH; also called ethyl alcohol, grain alcohol, drinking alcohol, or simply alcohol) is an organic compound. It is an Alcohol (chemistry), alcohol with the chemical formula . Its formula can be also written as or (an ethyl ...

) and

are coingested, via

hepatic The liver is a major organ only found in vertebrates which performs many essential biological functions such as detoxification of the organism, and the synthesis of proteins and biochemicals necessary for digestion and growth. In humans, it i ...

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. The reaction can ...

. 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 A drug overdose (overdose or OD) is the ingestion or application of a drug or other substance in quantities much greater than are recommended.

scenarios. However, the transesterfication process of methylphenidate to ethylphenidate, as tested in mice liver, was dominant in the inactive (−)-enantiomer but showed a prolonged and increased maximal plasma concentration of the active (+)-enantiomer of methylphenidate. Additionally, only a few percent of the consumed methylphenidate is converted to ethylphenidate. This

carboxylesterase The enzyme carboxylesterase (or carboxylic-ester hydrolase, EC 3.1.1.1; systematic name carboxylic-ester hydrolase) catalyzes reactions of the following form: :a carboxylic ester + H2O \rightleftharpoons an alcohol + a carboxylate Most enzymes f ...

-dependent transesterification process is also known to occur when

and alcohol are consumed together, forming

cocaethylene Cocaethylene (ethylbenzoylecgonine) is the ethyl ester of benzoylecgonine. It is structurally similar to cocaine, which is the methyl ester of benzoylecgonine. Cocaethylene is formed by the liver when cocaine and ethanol coexist in the blood. In ...

Pharmacodynamics

All available data on ethylphenidate's pharmacokinetics are drawn from studies conducted on rodents. Ethylphenidate is more selective to the

dopamine transporter The dopamine transporter (also dopamine active transporter, DAT, SLC6A3) is a membrane-spanning protein that pumps the neurotransmitter dopamine out of the synaptic cleft back into cytosol. In the cytosol, other transporters sequester the dopam ...

(DAT) than methylphenidate, having approximately the same efficacy as the parent compound, but has significantly less activity on the

norepinephrine transporter The norepinephrine transporter (NET), also known as noradrenaline transporter (NAT), is a protein that in humans is encoded by the solute carrier family 6 member 2 (SLC6A2) gene. NET is a monoamine transporter and is responsible for the sodium- ...

(NET). Its

dopaminergic Dopaminergic means "related to dopamine" (literally, "working on dopamine"), dopamine being a common neurotransmitter. Dopaminergic substances or actions increase dopamine-related activity in the brain. Dopaminergic brain pathways facilitate d ...

pharmacodynamic Pharmacodynamics (PD) is the study of the biochemical and physiologic effects of drugs (especially pharmaceutical drugs). The effects can include those manifested within animals (including humans), microorganisms, or combinations of organisms (for ...

profile is nearly identical to methylphenidate, and is primarily responsible for its

euphoric Euphoria ( ) is the experience (or affect) of pleasure or excitement and intense feelings of well-being and happiness. Certain natural rewards and social activities, such as aerobic exercise, laughter, listening to or making music and da ...

and reinforcing effects. The

eudysmic ratio The eudysmic ratio (also spelled eudismic ratio) represents the difference in pharmacologic activity between the two enantiomers of a drug. In most cases where a chiral compound is biologically active, one enantiomer is more active than the other. ...

for ethylphenidate is superior to that of methylphenidate. The following is ethylphenidate's binding profile in the mouse, alongside methylphenidate's. Figures for both the

racemic In chemistry, a racemic mixture, or racemate (), is one that has equal amounts of left- and right-handed enantiomers of a chiral molecule or salt. Racemic mixtures are rare in nature, but many compounds are produced industrially as racemates. ...

and the

dextrorotary Optical rotation, also known as polarization rotation or circular birefringence, is the rotation of the orientation of the plane of polarization about the optical axis of linearly polarized light as it travels through certain materials. Circul ...

enantiomer In chemistry, an enantiomer ( /ɪˈnænti.əmər, ɛ-, -oʊ-/ ''ih-NAN-tee-ə-mər''; from Ancient Greek ἐνάντιος ''(enántios)'' 'opposite', and μέρος ''(méros)'' 'part') – also called optical isomer, antipode, or optical ant ...

s are given:

Legality

* Ethylphenidate is not controlled internationally; see

Convention on Psychotropic Substances The Convention on Psychotropic Substances of 1971 is a United Nations treaty designed to control psychoactive drugs such as #Amphetamine-type stimulants, amphetamine-type stimulants, barbiturates, benzodiazepines, and Psychedelic drug, psychede ...

* Ethylphenidate is illegal in the

Netherlands ) , anthem = ( en, "William of Nassau") , image_map = , map_caption = , subdivision_type = Sovereign state , subdivision_name = Kingdom of the Netherlands , established_title = Before independence , established_date = Spanish Netherl ...

, as the

Opium Law The Opium Law (or ''Opiumwet'' in Dutch) is the section of the Dutch law which covers nearly all psychotropic drugs. Origin and history In 1912, the First International Opium Conference took place in The Hague, where agreements were made about ...

Lijst I covers it, as of 27 April 2018 * Ethylphenidate is not explicitly controlled in the US as part of the

Controlled Substances Act The Controlled Substances Act (CSA) is the statute establishing federal government of the United States, federal drug policy of the United States, U.S. drug policy under which the manufacture, importation, possession, use, and distribution of ...

but it could possibly be considered an analog of a Schedule II substance (methylphenidate) under the

Federal Analog Act The Federal Analogue Act, , is a section of the United States Controlled Substances Act passed in 1986 which allows any chemical "substantially similar" to a controlled substance listed in Controlled Substances Act#Schedule I controlled substance ...

if sold for human consumption. * Ethylphenidate is illegal in Sweden as of 15 December 2012. * Ethylphenidate is illegal to manufacture, distribute or import in the UK, as of 10 April 2015 it has been placed under a

Temporary Class Drug A temporary class drug is a relatively new status for controlled drugs, which has been adopted in some jurisdictions, notably New Zealand and the United Kingdom, to attempt to bring newly synthesised designer drugs under legal control. The controll ...

Order which automatically places it in a Class-B-like category. Though ordinarily the TCDO would only last 1 year, the ACMD reported that since its invocation prevalence of MPA had significantly decreased, and that it had been challenging to collect information about the drug. As a result of this, they requested that the TCDO be extended a further year from 26 June 2016. * Ethylphenidate is illegal in Jersey under the Misuse of Drugs (Jersey) Law 1978. * Australian state and federal legislation contains provisions that mean that analogues of controlled drugs are also covered by the legislation. Ethylphenidate would be an analogue of

under this legislation. * Ethylphenidate is controlled in Canada under the

Controlled Drugs and Substances Act The ''Controlled Drugs and Substances Act'' (french: Loi réglementant certaines drogues et autres substances) (the ''Act'') is Canada's federal drug control statute. Passed in 1996 under Prime Minister Jean Chrétien's government, it repeals ...

under Schedule III as of 05.05.2017. * Ethylphenidate is illegal in Germany as of 05.07.2013 * Ethylphenidate is illegal in Austria by the "Neue Psychoaktive Substanzen Gesetz" (=new psychoactive substances act) NPSG since 1 January 2012 * Ethylphenidate is illegal in Denmark as of 1 February 2013. * Ethylphenidate is illegal in Poland by "the Act on Counteracting Drug Addiction" since 1 July 2015 * It is illegal in Lithuania to use, buy, possess, transport, sell or import Ethylphenidate from 2015 * As of October 2015 Ethylphenidate is a controlled substance in China.

References

{{Monoamine reuptake inhibitors Alcohol Drug culture Ethyl esters 2-Benzylpiperidines Sympathomimetic amines Norepinephrine–dopamine reuptake inhibitors Stimulants Designer drugs Euphoriants

Pharmacokinetics

Pharmacodynamics

Legality

See also

References