title: Synthesis and pharmacology of ethylphenidate enantiomers: the human transesterification metabolite of methylphenidate and ethanol.
abstract: Ethanol elevates methylphenidate (1) plasma concentrations and yields the metabolite ethylphenidate (2). The therapeutic implications are under investigation. The IC(50) for dopamine reuptake inhibition by (+)-2 was 27 nM compared to 367 nM for cocaine and 1730 nM for (-)-2. Binding selectivity for dopamine versus norepinephrine transporters was greater for (+)-2 than for cocaine. Intraperitoneal (+)-2 was approximately half as active as (+)-1 in stimulating mouse motor activity at 5 mg/kg, but (+)-2 was as active as (+)-1 at 10 mg/kg.
authors.affiliation: Department of Pharmaceutical Sciences, Medical University of South Carolina, Charleston, South Carolina 29425, USA. patrickk@musc.edu
authors.forename: Kennerly S
authors.initials: KS
authors.lastname: Patrick
authors.forename: Robin L
authors.initials: RL
authors.lastname: Williard
authors.forename: Adam L
authors.initials: AL
authors.lastname: VanWert
authors.forename: Justin J
authors.initials: JJ
authors.lastname: Dowd
authors.forename: John E
authors.initials: JE
authors.lastname: Oatis
authors.forename: Lawrence D
authors.initials: LD
authors.lastname: Middaugh
mesh_terms: D000818:Animals; D002460:Cell Line; D003042:Cocaine / Q000378:metabolism; D050483:Dopamine Plasma Membrane Transport Proteins; D004951:Esterification; D000431:Ethanol / Q000378:metabolism*; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism; D026901:Membrane Transport Proteins / Q000378:metabolism; D008774:Methylphenidate / Q000031:analogs & derivatives* / Q000737:chemistry* / Q000378:metabolism* / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000187:drug effects; D009419:Nerve Tissue Proteins / Q000378:metabolism; D050484:Norepinephrine Plasma Membrane Transport Proteins; D011485:Protein Binding; D011869:Radioligand Assay; D011954:Receptors, Dopamine / Q000378:metabolism; D011985:Receptors, Serotonin / Q000378:metabolism; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D027981:Symporters / Q000378:metabolism
chemical_list: D050483:Dopamine Plasma Membrane Transport Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D050484:Norepinephrine Plasma Membrane Transport Proteins; D011954:Receptors, Dopamine; D011985:Receptors, Serotonin; C493227:SLC6A2 protein, human; C493228:Slc6a2 protein, mouse; D027981:Symporters; D008774:Methylphenidate; D000431:Ethanol; C042400:ethylphenidate; D003042:Cocaine