Displacement of RTI-55 from the dopamine transporter by cocaine

Eur J Pharmacol. 1996 Jan 25;296(2):145-51. doi: 10.1016/0014-2999(95)00698-2.


The cocaine analog 3 beta-(4-iodophenyl)tropane-2 beta-carboxylic acid methyl ester (RTI-55 or beta CIT) has a higher affinity for the dopamine transporter and may be potentially useful in interfering with cocaine's actions in brain. However, imaging studies have demonstrated displacement of tracer doses of [123I]RTI-55 by a subsequent dose of cocaine. Similar displacement of pharmacological doses of RTI-55 might compromize therapy with RTI-55 in cocaine abuse. The reduction in dopamine transporter availability, assessed in vivo in mouse striatum using [3H]cocaine, caused by pretreatment with RTI-55 was significantly mitigated by subsequent administration of cocaine. In a similar experiment using a tracer dose of [123I]RTI-55 significant reductions of striatal radioligand binding by pretreatment with cocaine or RTI-55 were not observed. These results suggest that: (1) cocaine can displace pharmacological doses of RTI-55 from striatum, and (2) radioligands used to assess binding site occupancy should have a lower affinity than the occupying drug.

Publication types

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

MeSH terms

  • Animals
  • Binding, Competitive
  • Brain / metabolism
  • Carrier Proteins / metabolism*
  • Cocaine / analogs & derivatives*
  • Cocaine / metabolism*
  • Dopamine / metabolism*
  • Dopamine Plasma Membrane Transport Proteins
  • Iodine Radioisotopes
  • Male
  • Membrane Glycoproteins*
  • Membrane Transport Proteins*
  • Mice
  • Nerve Tissue Proteins*
  • Radioligand Assay
  • Tritium


  • Carrier Proteins
  • Dopamine Plasma Membrane Transport Proteins
  • Iodine Radioisotopes
  • Membrane Glycoproteins
  • Membrane Transport Proteins
  • Nerve Tissue Proteins
  • Tritium
  • 2beta-carbomethoxy-3beta-(4-iodophenyl)tropane
  • Cocaine
  • Dopamine