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

Eur J Pharmacol. 1988 Apr 13;148(3):427-36. doi: 10.1016/0014-2999(88)90122-7.

Abstract

A benzothiophenyl 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 (IC50 = 7 nM). This compound also has low affinity for the PCP receptor (K0.5 = 6 microM). The sodium-dependent [3H]BTCP binding to rat striatal membranes was investigated. [3H]BTCP bound to two different sites: one with very high affinity (Kd1 = 0.9 nM, Bmax1 = 3.5 pmol/mg protein) which paralleled the distribution of dopaminergic nerve endings and a second with lower affinity (Kd2 = 20 nM, Bmax2 = 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Corpus Striatum / metabolism
  • Dopamine / metabolism*
  • In Vitro Techniques
  • Phencyclidine / analogs & derivatives*
  • Phencyclidine / pharmacology
  • Radioligand Assay
  • Rats
  • Rats, Inbred Strains
  • Receptors, Dopamine / drug effects*
  • Synaptosomes / metabolism
  • Tritium

Substances

  • Receptors, Dopamine
  • Tritium
  • 1-(1-(2-benzo(b)thienyl)cyclohexyl)piperidine
  • Phencyclidine
  • Dopamine