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Dopamine transporter uptake blockers Structure-activity relationships

The dopamine transporter (DAT), a protein located on presynaptic nerve terminals (4), plays a major role in the reuptake of released dopamine. Uptake of DA is sodium- and chloride Ion-, as well as temperature- and lime-dependent, and is inhibited by a variety of compounds, including cocaine. Even though cocaine binds to several sites in the brain, only binding potencies at the DA site have been shown to correlate with the reinforcing properties of cocaine in animal models, which are the primary factors in its abuse. Thus, the DAT has been called a cocaine receptor (21) and may be the initial site responsible for producing cocaine's drug reinforcement. The cDNA for the DAT has been cloned from rat (3), bovine (88), and human (92) brains. The hydrophobicity profile indicates 12 possible membrane-spanning regions with the ammo and carboxy termini located intracellularly. The protein from human and rat brains contains three and four extracellular N-glycosylation sites, respectively.


Carroll, F., Lewin, A., & Kuhar, M. (1996). Dopamine transporter uptake blockers: Structure-activity relationships. In MEA. Reith (Ed.), Neurotransmitter Transporters: Structure, Function, and Regulation (pp. 263-296). Totowa, NJ: Humana Press.