title: 1-[1-2-Benzo[b]thiopheneyl)cyclohexyl]piperidine hydrochloride (BTCP) yields two active primary metabolites in vitro: synthesis, identification from rat liver microsome extracts, and affinity for the neuronal dopamine transporter.
abstract: 1-[1-(2-Benzo[b]thiopheneyl)cyclohexyl]piperidine hydrochloride (BTCP, 1) and cocaine bind to the neuronal dopamine transporter to inhibit dopamine (DA) reuptake. However, on chronic administration, cocaine produces sensitization, but 1 produces tolerance. Because metabolites of 1 might be responsible for some of its pharmacological properties, we have identified the primary metabolites of 1 produced by rat liver microsomes and determined their affinities for the DA transporter. Five monohydroxylated derivatives (3, 5, 9, 10, 14) and two degradation compounds (15, 16) were identified as metabolites through comparison with synthetic standards in HPLC and GC systems. Standards were obtained utilizing synthetic schemes previously used for the synthesis of phencyclidine metabolites. In vitro, two compounds (3, 5) showed a high affinity for the DA transporter. These active metabolites might be important in the pharmacology of 1.
authors.affiliation: CNRS ERS 155, INSERM U 249, Montpellier, France.
authors.forename: C
authors.initials: C
authors.lastname: Deleuze-Masquefa
authors.forename: M
authors.initials: M
authors.lastname: Michaud
authors.forename: J
authors.initials: J
authors.lastname: Vignon
authors.forename: J M
authors.initials: JM
authors.lastname: Kamenka
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D018491:Dopamine Agonists / Q000138:chemical synthesis* / Q000378:metabolism; D050483:Dopamine Plasma Membrane Transport Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D008862:Microsomes, Liver / Q000378:metabolism*; D009419:Nerve Tissue Proteins; D010622:Phencyclidine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000378:metabolism; D051381:Rats; D013329:Structure-Activity Relationship
chemical_list: D002352:Carrier Proteins; D018491:Dopamine Agonists; D050483:Dopamine Plasma Membrane Transport Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; C056415:1-(1-(2-benzo(b)thienyl)cyclohexyl)piperidine; D010622:Phencyclidine