Ethylphenidate

drugbox
IUPAC_name = ethyl 2-phenyl-2-piperidin-2-ylacetate

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CAS_number = 57413-43-1
ATC_prefix =
ATC_suffix =
PubChem = 3080846
DrugBank =
C=15|H=21|N=1|O=2
molecular_weight = 247.33274 g/mol
smiles = CCOC(=O)C(C1CCCCN1)C2=CC=CC=C2
bioavailability = Variable
protein_bound = Unknown
metabolism = Hepatic transesterification of prodrugs methylphenidate and ethanol
elimination_half-life = Dependent on methylphenidate administrationMarkowitz JS, DeVane CL, Boulton DW, Nahas Z, Risch SC, Diamond F, Patrick KS. Ethylphenidate formation in human subjects after the administration of a single dose of methylphenidate and ethanol. "Drug Metabolism and Disposition". 2000 Jun;28(6):620-4.]
excretion = Urine
pregnancy_AU =
pregnancy_US =
pregnancy_category=
legal_AU =
legal_CA =
legal_UK =
legal_US =
legal_status = Presumably Controlled in the US
routes_of_administration = N/A

Enantiomeric (dl)-"threo"-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 neaurotransmitters in the brain, by binding to, and partially blocking the transporter proteins that normally remove those monoamines from the synaptic cleft. It is 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 abuse or overdose scenarios. [Markowitz JS, Logan BK, Diamond F, Patrick KS. Detection of the novel metabolite ethylphenidate after methylphenidate overdose with alcohol coingestion. "Journal of Clinical Psychopharmacology". 1999 Aug;19(4):362-6.] This carboxylesterase-dependent transesterification process is also known to occur when cocaine and alcohol are consumed together, forming cocaethylene. [Bourland JA, Martin DK and Mayersohn M (1997) Carboxylesterase transesterification of meperidine (Demerol) and methylphenidate (Ritalin) in the presence of [2H6] ethanol: Preliminary in vitro findings using a rat liver preparation. J Pharm Sci 86: 1494-1496]

Ethylphenidate is more selective to the dopamine transporter (DAT) than methylphenidate, having approximately the same efficacy as the parent compound, [Patrick KS, Williard RL, VanWert AL, Dowd JJ, Oatis JE Jr, Middaugh LD. Synthesis and pharmacology of ethylphenidate enantiomers: the human transesterification metabolite of methylphenidate and ethanol. "Journal of Medicinal Chemistry". 2005 Apr 21;48(8):2876-81.] but has significantly less activity on the norepinephrine transporter (NET). [Williard RL, Middaugh LD, Zhu HJ, Patrick KS. Methylphenidate and its ethanol transesterification metabolite ethylphenidate: brain disposition, monoamine transporters and motor activity. "Behavioural Pharmacology". 2007 Feb;18(1):39-51.] It has nearly a identical dopaminergic pharmacodynamic profile as methylphenidate, possessing appreciable affinity for the inhibitory G protein-coupled dopamine subtype-2 receptors in the striatum and mesolimbic regions of the brain, [Schweri MM, Skolnick P, Rafferty MF, Rice KC, Janowsky AJ and Paul SM (1985) [3H] Threo-(±)-methylphenidate binding to 3,4-dihydroxyphenylethylamine uptake sites in corpus striatum: Correlation with the stimulant properties of ritalinic acid esters. J Neurochem 45: 1062-1070] including the nucleus accumbens, [Volkow ND, Ding Y-S, Wang G-L, Logan J, Gatley JS, Dewey S, Ashby C, Lieberman J, Hitzemann R and Wolf AP (1995) Is methylphenidate like cocaine? Studies on their pharmacokinetics and distribution in the human brain. Arch Gen Psychiatry 52: 456-463] which is primarily responsible for its pro-euphorant and reinforcing effects. [Jatlow P, Elsworth JD, Bradberry CW, Winger G, Taylor JR, Russell R and Roth RH (1991) Cocaethylene: A neuropharmacologically active metabolite associated with concurrent cocaine-ethanol ingestion. Life Sci 48: 1787-1794]

References

ee also

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