Ethylphenidate
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| Systematic (IUPAC) name | |
| (RS)-ethyl 2-phenyl-2-piperidin-2-ylacetate | |
| Clinical data | |
| Pregnancy cat. | ? |
| Legal status | Unregulated / not available as Rx; "not illegal" (US) |
| Routes | N/A |
| Pharmacokinetic data | |
| Bioavailability | Variable |
| Protein binding | Unknown |
| Metabolism | Hepatic transesterification of prodrugs methylphenidate and ethanol |
| Half-life | Dependent on methylphenidate administration.[1] |
| Excretion | Urine |
| Identifiers | |
| CAS number | 57413-43-1  |
| ATC code | None |
| PubChem | CID 3080846 |
| ChemSpider | 2338571 |
| Chemical data | |
| Formula | C15H21NO2 |
| Mol. mass | 247.33274 g/mol |
| SMILES | eMolecules & PubChem |
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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.
It is most commonly formed 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]
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] It has a near-identical dopaminergic pharmacodynamic profile as methylphenidate, which is primarily responsible for its euphoric and reinforcing effects.[6]
Interestingly, the eudysmic ratio for ethylphenidate is superior to that seen for methylphenidate.[4]
| Compound[5] | Binding DAT | Binding NET | Uptake DA | Uptake NE |
|---|---|---|---|---|
| d-TMP | 139 | 408 | 28 | 46 |
| d-TEP | 276 | 2479 | 24 | 247 |
| dl-TMP | 105 | 1560 | 24 | 31 |
| dl-TEP | 382 | 4824 | 82 | 408 |
TEP is less stimulatory than TMP at 5mg/kg, although both compounds generalize at 10mg/kg. This is suggestive of a noradrenergic stimulatory effect present for TMP at lower doses.
[edit] Legality
- Ethylphenidate is controlled by the US federal analogue act as an analogue of methylphenidate.
- Ethylphenidate is legal in the UK, as there is no catch-all act for ritalinic esters, nor is it explicitly named in the Misuse of Drugs Act
- Ethylphenidate is covered by the Australian analogue act as an analogue of ketamine "alkyl, alkenyl or alkynyl groups with up to 6 carbon
atoms in the group, where the group is attached to oxygen (for example, an ester or an ether group),nitrogen, sulphur or carbon;"
[edit] References
- ^ a b Markowitz, JS; Devane, CL; Boulton, DW; Nahas, Z; Risch, SC; Diamond, F; Patrick, KS (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): 620–4. PMID 10820132.
- ^ 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.
- ^ 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.
- ^ a b 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.
- ^ 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.
- ^ Jatlow, P; Elsworth, JD; Bradberry, CW; Winger, G; Taylor, JR; Russell, R; Roth, RH (1991). "Cocaethylene: a neuropharmacologically active metabolite associated with concurrent cocaine-ethanol ingestion". Life sciences 48 (18): 1787–94. doi:10.1016/0024-3205(91)90217-Y. PMID 2020260.
[edit] See also
- Cocaethylene (compound formed when cocaine and ethanol are taken together)
- Methylphenidate
- Ethanol (drinking alcohol)
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