Ethylphenidate

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Ethylphenidate
Systematic (IUPAC) name
(RS)-ethyl 2-phenyl-2-piperidin-2-ylacetate
Clinical data
Legal statusUnscheduled (US)
RoutesInsufflation, Vaporized, Intravenous, Intramuscular, Rectal, Oral, Sublingual
Pharmacokinetic data
BioavailabilityVariable
Protein bindingUnknown
MetabolismHepatic transesterification of prodrugs methylphenidate and ethanol
Half-lifeLess than 4hrs[note 1][citation needed]
ExcretionUrine
Identifiers
CAS number57413-43-1 YesY
ATC codeNone
PubChemCID 3080846
ChemSpider2338571 YesY
Chemical data
FormulaC15H21NO2 
Mol. mass247.33274 g/mol
 YesY (what is this?)  (verify)
 
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Ethylphenidate
Systematic (IUPAC) name
(RS)-ethyl 2-phenyl-2-piperidin-2-ylacetate
Clinical data
Legal statusUnscheduled (US)
RoutesInsufflation, Vaporized, Intravenous, Intramuscular, Rectal, Oral, Sublingual
Pharmacokinetic data
BioavailabilityVariable
Protein bindingUnknown
MetabolismHepatic transesterification of prodrugs methylphenidate and ethanol
Half-lifeLess than 4hrs[note 1][citation needed]
ExcretionUrine
Identifiers
CAS number57413-43-1 YesY
ATC codeNone
PubChemCID 3080846
ChemSpider2338571 YesY
Chemical data
FormulaC15H21NO2 
Mol. mass247.33274 g/mol
 YesY (what is this?)  (verify)

Ethylphenidate (EP) 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 neurotransmitters in the brain, by binding to, and partially blocking the transporter proteins that normally remove those monoamines from the synaptic cleft.

Effects[edit]

As an analogue to the prescription-only stimulant drug methylphenidate (Ritalin), subjective effects are comparable. Due to the illicit nature of manufacture and the potential for psychoactive impurities, side effects can be unpredictable.[citation needed] Some anecdotal user reports indicate that even just a few uses via the insufflation (snorted) route of administration can result in a perforated septum.[1][2][3]

Pharmacokinetics[edit]

Ethylphenidate can be formed in-vivo when ethanol and methylphenidate are coingested, via hepatic transesterification.[4] 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.[5] This carboxylesterase-dependent transesterification process is also known to occur when cocaine and alcohol are consumed together, forming cocaethylene.[6] 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[7] Additionally, only a few percent of the consumed methylphendiate is converted to ethylphenidate so a pharmacologically significant dose would never be produced.[4]

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,[7] but has significantly less activity on the norepinephrine transporter (NET).[8] Its dopaminergic pharmacodynamic profile is nearly identical to methylphenidate, and is primarily responsible for its euphoric and reinforcing effects.[9]

The eudysmic ratio for ethylphenidate is superior to that of methylphenidate.[7]

The following is ethylphenidate's binding profile in the mouse, alongside methylphenidate's. Figures for both the racemic and the dextrorotary enantiomers are given:[8]

CompoundBinding DATBinding NETUptake DAUptake NE
d-methylphenidate1394082846
d-ethylphenidate276247924247
dl-methylphenidate10515602431
dl-ethylphenidate382482482408

Legality[edit]

Notes[edit]

  1. ^ Shorter lasting than methylphenidate according to subjective reports

References[edit]

  1. ^ http://www.bluelight.ru/vb/threads/611962-ethylphenidate-dosage?p=10369068&viewfull=1#post10369068
  2. ^ http://www.drugs-forum.com/forum/showthread.php?t=156994
  3. ^ http://www.ukchemicalresearch.org/Thread-Ethylphenidate
  4. ^ 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
  5. ^ 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
  6. ^ 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
  7. ^ 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
  8. ^ 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
  9. ^ 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
  10. ^ http://www.riksdagen.se/sv/Dokument-Lagar/Lagar/Svenskforfattningssamling/Forordning-19921554-om-kont_sfs-1992-1554/?bet=1992:1554
  11. ^ http://laws-lois.justice.gc.ca/eng/acts/C-38.8/page-26.html#h-30

See also[edit]