Differential relationships among dopamine transporter affinities and stimulant potencies of various uptake inhibitors

Eur J Pharmacol. 1994 Oct 3;263(3):277-83. doi: 10.1016/0014-2999(94)90723-4.


Binding to the dopamine transporter and inhibiting dopamine reuptake are considered important factors in regulating behavioral effects of cocaine. One prominent behavioral effect of cocaine and other dopamine uptake inhibitors is the stimulation of locomotor activity. To examine the relationship between action at the dopamine transporter and behavior, the displacement of [3H]WIN 35,428 (CFT naphthalene sulfate; 2-beta-carbomethoxy-3-beta-(4-fluorophenyl)tropane-1,5-naphthalene disulfonate) binding in rat caudate putamen by cocaine and other uptake inhibitors was compared with stimulation of mouse locomotor activity. There was a significant correlation among affinities for binding and potencies for stimulating activity for cocaine and structurally similar compounds. For structurally dissimilar uptake inhibitors, however, there was no significant correlation among potencies for stimulation of activity and affinity for displacement of [3H]WIN 35,428 binding. These findings provide evidence that cocaine analogs may bind to the dopamine transporter in a manner that is fundamentally different from that for structurally dissimilar uptake inhibitors.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Binding, Competitive
  • Carrier Proteins / metabolism*
  • Caudate Nucleus / drug effects
  • Caudate Nucleus / metabolism
  • Cocaine / administration & dosage
  • Cocaine / analogs & derivatives*
  • Cocaine / metabolism
  • Cocaine / pharmacology
  • Computer Simulation
  • Dopamine Antagonists / administration & dosage
  • Dopamine Antagonists / metabolism
  • Dopamine Antagonists / pharmacology*
  • Dopamine Plasma Membrane Transport Proteins
  • Male
  • Membrane Glycoproteins*
  • Membrane Transport Proteins*
  • Mice
  • Motor Activity / drug effects*
  • Nerve Tissue Proteins*
  • Rats
  • Rats, Sprague-Dawley
  • Structure-Activity Relationship


  • Carrier Proteins
  • Dopamine Antagonists
  • Dopamine Plasma Membrane Transport Proteins
  • Membrane Glycoproteins
  • Membrane Transport Proteins
  • Nerve Tissue Proteins
  • (1R-(exo,exo))-3-(4-fluorophenyl)-8-methyl-8- azabicyclo(3.2.1)octane-2-carboxylic acid, methyl ester
  • Cocaine