Evidence for mutually exclusive binding of cocaine, BTCP, GBR 12935, and dopamine to the dopamine transporter

Eur J Pharmacol. 1992 Dec 1;227(4):417-25. doi: 10.1016/0922-4106(92)90160-w.


The present study addressed the possibility that there are distinct but allosterically interacting populations of binding sites for dopamine/cocaine and BTCP/GBR (N-[1-(2-benzo[b]thiophenyl)cyclohexyl]piperidine/1-(2-diphenylmethox y) - ethyl]-4-(3-phenylpropyl)piperazine) (selective dopamine uptake blockers) on the dopamine transporter in the rat striatum. Dopamine uptake sites were labeled in vitro with the cocaine analog [3H]CFT (2 beta-carbomethoxy-3 beta-(4-fluorophenyl)-tropane), and the inhibition of binding by CFT or cocaine was measured. A graphic method was adopted for studying shifts in inhibitory potency resulting from the addition of a second compound. Under the conditions used, the co-presence of dopamine, GBR 12935, or BTCP decreased the inhibitory potency of CFT or cocaine to the extent predicted by a model in which all compounds bind to the same site or the binding of all compounds is mutually exclusive. No evidence for negative allosteric interactions between CFT and BTCP was found in experiments comparing inhibition of [3H]CFT binding by BTCP at a low and high concentration of [3H]CFT.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Binding Sites / drug effects
  • Binding, Competitive
  • Cocaine / metabolism*
  • Corpus Striatum / drug effects
  • Corpus Striatum / metabolism
  • Dopamine / metabolism*
  • Dopamine Antagonists
  • Female
  • Phencyclidine / analogs & derivatives*
  • Phencyclidine / metabolism
  • Piperazines / metabolism*
  • Rats
  • Rats, Sprague-Dawley


  • Dopamine Antagonists
  • Piperazines
  • 1-(1-(2-benzo(b)thienyl)cyclohexyl)piperidine
  • 1-(2 (diphenylmethoxy)ethyl)-4-(3-phenylpropyl)piperazine
  • Cocaine
  • Phencyclidine
  • Dopamine