Ethylphenidate

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Ethylphenidate
Ethylphenidate.svg
Ethylphenidate-3D-ball-model.png
Systematic (IUPAC) name
(RS)-ethyl 2-phenyl-2-piperidin-2-ylacetate
Clinical data
Trade names EPH
Legal status
  • Unscheduled (US) (UK)
Routes Insufflation, Vaporized, Intravenous, Intramuscular, Rectal, Oral, Sublingual
Pharmacokinetic data
Bioavailability Variable
Protein binding Unknown
Metabolism Hepatic transesterification of prodrugs methylphenidate and ethanol
Half-life Less than 4hrs[note 1][citation needed]
Excretion Urine
Identifiers
CAS number 57413-43-1 YesY
ATC code None
PubChem CID 3080846
ChemSpider 2338571 YesY
Chemical data
Formula C15H21NO2 
Mol. mass 247.33274 g/mol
 YesY (what is this?)  (verify)

Ethylphenidate (EPH) is a psychostimulant and a close analog of methylphenidate. The two drugs have very similar pharmacological effects.[medical citation needed]

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.

Pharmacokinetics[edit]

Ethylphenidate can be formed in vivo when ethanol and methylphenidate are coingested, via hepatic transesterification.[1] 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.[2] This carboxylesterase-dependent transesterification process is also known to occur when cocaine and alcohol are consumed together, forming cocaethylene.[3] 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 (+)-enanatiomer of methylphenidate.[4] Additionally, only a few percent of the consumed methylphenidate is converted to ethylphenidate so a pharmacologically significant dose would never be produced.[1]

Pharmacodynamics[edit]

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,[4] but has significantly less activity on the norepinephrine transporter (NET).[5] Its dopaminergic pharmacodynamic profile is nearly identical to methylphenidate, and is primarily responsible for its euphoric and reinforcing effects.[6]

The eudysmic ratio for ethylphenidate is superior to that of methylphenidate.[4][not in citation given]

The following is ethylphenidate's binding profile in the mouse, alongside methylphenidate's. Figures for both the racemic and the dextrorotary enantiomers are given:[5]

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[edit]

  • 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.
  • Ethylphenidate is illegal in Sweden as of 15 December 2012.[7]
  • Ethylphenidate is not controlled in the UK, as there is no generic legislation for ritalinic esters, nor is it explicitly named in the Misuse of Drugs Act
  • Ethylphenidate is illegal in Jersey under the Misuse of Drugs (Jersey) Law 1978.[8]
  • 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.[citation needed]
  • 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).[9]
  • Ethylphenidate is illegal in Germany as of 05.07.2013 [10]
  • 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.[11]

Notes[edit]

  1. ^ Shorter lasting than methylphenidate according to subjective reports

References[edit]

  1. ^ a b Markowitz, J. S.; Devane, C. L.; Boulton, D. W.; Nahas, Z.; Risch, S. C.; Diamond, F.; Patrick, K. S. (2000). "Ethylphenidate formation in human subjects after the administration of a single dose of methylphenidate and ethanol". Drug metabolism and disposition: the biological fate of chemicals 28 (6): 620–624. PMID 10820132.  edit
  2. ^ Markowitz, J. S.; Logan, B. K.; Diamond, F.; Patrick, K. S. (1999). "Detection of the novel metabolite ethylphenidate after methylphenidate overdose with alcohol coingestion". Journal of Clinical Psychopharmacology 19 (4): 362–366. doi:10.1097/00004714-199908000-00013. PMID 10440465.  edit
  3. ^ Bourland, J.; Martin, D.; Mayersohn, M. (1997). "Carboxylesterase-mediated transesterification of meperidine (Demerol) and methylphenidate (Ritalin) in the presence of 2H6ethanol: preliminary in vitro findings using a rat liver preparation". Journal of pharmaceutical sciences 86 (12): 1494–1496. doi:10.1021/js970072x. PMID 9423167.  edit
  4. ^ a b c Patrick, K.; Williard, R.; Vanwert, A.; Dowd, J.; Oatis, J.; Middaugh, L. (2005). "Synthesis and pharmacology of ethylphenidate enantiomers: the human transesterification metabolite of methylphenidate and ethanol". Journal of Medicinal Chemistry 48 (8): 2876–2881. doi:10.1021/jm0490989. PMID 15828826.  edit
  5. ^ a b Williard, R.; Middaugh, L.; Zhu, H.; Patrick, K. (2007). "Methylphenidate and its ethanol transesterification metabolite ethylphenidate: brain disposition, monoamine transporters and motor activity". Behavioural Pharmacology 18 (1): 39–51. doi:10.1097/FBP.0b013e3280143226. PMID 17218796.  edit
  6. ^ Jatlow, P.; Elsworth, J. D.; Bradberry, C. W.; Winger, G.; Taylor, J. R.; Russell, R.; Roth, R. H. (1991). "Cocaethylene: a neuropharmacologically active metabolite associated with concurrent cocaine-ethanol ingestion". Life Sciences 48 (18): 1787–1794. doi:10.1016/0024-3205(91)90217-Y. PMID 2020260.  edit
  7. ^ http://www.riksdagen.se/sv/Dokument-Lagar/Lagar/Svenskforfattningssamling/Forordning-19921554-om-kont_sfs-1992-1554/?bet=1992:1554
  8. ^ http://www.jerseylaw.je/law/Display.aspx?url=/law/lawsinforce/consolidated/08/08.680.60_MisuseofDrugs(GeneralProvisions)Order2009_RevisedEdition_1January2014.pdf
  9. ^ http://laws-lois.justice.gc.ca/eng/acts/C-38.8/page-26.html#h-30
  10. ^ http://www.gesetze-im-internet.de/btmg_1981/anlage_ii_60.html
  11. ^ https://www.retsinformation.dk/Forms/R0710.aspx?id=145195

See also[edit]