Ethylphenidate

Ethylphenidate

Systematic (IUPAC) name
(RS)-ethyl 2-phenyl-2-piperidin-2-ylacetate
Clinical data
Trade names	EPH
Legal status	DE: Anlage II (Prohibited) UK: Class B Temporary Class Drug
Routes of administration	Insufflation, vaporized, intravenous, intramuscular, rectal, oral, sublingual
Pharmacokinetic data
Bioavailability	Variable
Protein binding	Unknown
Metabolism	Hepatic transesterification of prodrugs methylphenidate and ethanol
Biological half-life	Less than 4hrs
Excretion	Urine
Identifiers
CAS Number	57413-43-1 Y
ATC code	none
PubChem	CID: 3080846
ChemSpider	2338571 Y
Chemical data
Formula	C15H21NO2
Molecular mass	247.33274 g/mol
SMILES CCOC(=O)C(C1CCCCN1)C2=CC=CC=C2
InChI InChI=1S/C15H21NO2/c1-2-18-15(17)14(12-8-4-3-5-9-12)13-10-6-7-11-16-13/h3-5,8-9,13-14,16H,2,6-7,10-11H2,1H3 Y Key:AIVSIRYZIBXTMM-UHFFFAOYSA-N Y
(verify)

Ethylphenidate (EPH) is a psychostimulant and a close analog of methylphenidate.

Ethylphenidate acts as both a dopamine reuptake inhibitor and norepinephrine reuptake inhibitor, meaning it effectively boosts the levels of the norepinephrine and dopamine neurotransmitters in the brain, by binding to, and partially blocking the transporter proteins that normally remove those monoamines from the synaptic cleft.

There have been anecdotal reports of a perforated septum resulting from even just a few uses of ethylphenidate by insufflation (snorting). This is almost certainly due to ethylphenidate being caustic or containing caustic impurities, as users report that insufflation is extremely painful.

Pharmacokinetics

Ethylphenidate can be formed in vivo 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. 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 so a pharmacologically significant dose would never be produced. Ethylphenidate also metabolizes into methylphenidate and ritalinic acid.

Pharmacodynamics

All available data on ethylphenidate's pharmacokinetics are drawn from studies conducted on rodents. 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). Its dopaminergic pharmacodynamic profile is nearly identical to methylphenidate, and is primarily responsible for its euphoric and reinforcing effects.

The eudysmic ratio 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 and the dextrorotary enantiomers are given:

Compound	Binding DAT	Binding NET	Uptake DA	Uptake NE
d-methylphenidate	139	408	28	46
d-ethylphenidate	276	2479	24	247
dl-methylphenidate	105	1560	24	31
dl-ethylphenidate	382	4824	82	408

Legality

• Ethylphenidate is not controlled internationally; see Convention on Psychotropic Substances
• Ethylphenidate is not controlled in the Netherlands, as the Opium Law does not cover it, nor is there any law covering analogs of controlled drugs (methylphenidate is covered).
• Ethylphenidate is not explicitly controlled in US but it could possibly be considered an analog of a Schedule II substance (methylphenidate) under the Federal Analog Act 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 Order which automatically places it in the Class B category.
• 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 methylphenidate under this legislation.
• Ethylphenidate is not controlled in Canada under the Controlled Drugs and Substances Act as the inclusion of methylphenidate in Schedule III only bans salts, not analogues (unlike drugs covered by Schedule I).
• 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
• As of October 2015 Ethylphenidate is a controlled substance in China.

See also

• 3,4-Dichloromethylphenidate
• HDEP-28
• HDMP-28
• Naphthylisopropylamine
• Naphyrone
• 2β-Propanoyl-3β-(2-naphthyl)-tropane (WF-23)
• Isopropylphenidate
• Propylphenidate

See also

• Cocaethylene (compound formed when cocaine and ethanol are taken together)
• Methylphenidate
• Ethanol (drinking alcohol)