Dopamine transporter as target for drug development of cocaine dependence medications

Eur J Pharmacol. 2003 Oct 31;479(1-3):93-106. doi: 10.1016/j.ejphar.2003.08.060.

Abstract

Because much evidence implicates the dopamine transporter in the reinforcing effects of cocaine, development of potential medications for cocaine dependence has included the dopamine transporter as a target. The present overview covers progress in the drug development area regarding several classes of dopamine uptake inhibitors, with an emphasis on structure-activity relationships that enhance potency and selectivity at transporters for dopamine compared with those for serotonin or norepinephrine. The following categories of compounds are covered: tropane, benztropine, 1-[2-[bis(4-fluorophenyl)methoxy]ethyl]-4-(3-phenylpropyl)piperazine (GBR), methylphenidate, mazindol, and phencyclidine analogs. Activity at transporters as well as on behavior is highlighted.

Publication types

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

MeSH terms

  • Animals
  • Cocaine-Related Disorders / drug therapy*
  • Cocaine-Related Disorders / metabolism
  • Dopamine Plasma Membrane Transport Proteins
  • Dopamine Uptake Inhibitors / administration & dosage*
  • Dopamine Uptake Inhibitors / chemistry
  • Dopamine Uptake Inhibitors / metabolism
  • Drug Delivery Systems / methods*
  • Humans
  • Membrane Glycoproteins*
  • Membrane Transport Modulators*
  • Membrane Transport Proteins / antagonists & inhibitors*
  • Membrane Transport Proteins / metabolism
  • Nerve Tissue Proteins / antagonists & inhibitors*
  • Nerve Tissue Proteins / metabolism

Substances

  • Dopamine Plasma Membrane Transport Proteins
  • Dopamine Uptake Inhibitors
  • Membrane Glycoproteins
  • Membrane Transport Modulators
  • Membrane Transport Proteins
  • Nerve Tissue Proteins