Monoamine transporters and psychostimulant drugs.
Most psychostimulants interact with monoamine transport proteins. This paper reviews work our laboratory has conducted to investigate the interaction of psychostimulants with monoamine transporters in order to advance our understanding of how these drugs affect the brain. We review two topics: (1) characterization of multiple binding sites for cocaine-like drugs and (2) an examination of the mechanisms of action of amphetamine-type anorectic agents. We conclude that the brain contains high abundance nonclassical binding sites for cocaine-like drugs that have micromolar affinity for cocaine and that none of the clinically available amphetamine-type appetite suppressants are equipotent substrates for dopamine transporter (DAT) and serotonin transporter (SERT) proteins. Future medications discovery efforts should focus on identifying new compounds which possess the equipotent substrate activity at DAT and SERT, but which lack the adverse effects of stimulants developed decades ago.[1]References
- Monoamine transporters and psychostimulant drugs. Rothman, R.B., Baumann, M.H. Eur. J. Pharmacol. (2003) [Pubmed]
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