3H]N-[1-(2-Benzo(b)thiophenyl) cycohexyl]piperidine ([ 3H]BTCP): a new phencyclidine analog selective for the dopamine uptake complex

Abstract

A benzothiopenyl group instead of a phenyl ring on phencyclidine (PCP) yields a molecule N-[1-(2-benzo( (b)thiophenyl)cyclohexyl]piperidine (BTCP), which is one of the more potent known dopamine (DA) uptake inhibitors (IC 50=7 nM). This compound also has low affinity for the PCP receptor (K 0.5=6 μM). The sodium-dependent [ 3H]BTCP binding to rat striatal membranes was investigated. [ 3H]BTCP bound to two different sites: one with very high affinity (K d1=0.9 nM, B max1=3.5 pmol/mg protein) which paralleled the distribution of dopaminergic nerve endings and a second with lower affinity (K d2=20 nM, B max2=7.5 pmol/mg protein). There was a good correlation between the abilities of drugs specific for the DA uptake complex and of PCP analogs to inhibit high affinity [ 3H]BTCP binding and [ 3H]DA synaptosomal uptake. This study also demonstrated that PCP interacts with the DA uptake site since it is a competitive inhibitor of high affinity [ 3H]BTCP binding. This site, however, is not the PCP receptor, which has a different pharmacological selectivity.