Cocaine's reinforcing effects are believed to be related to its ability to inhibit dopamine uptake. From behavioral studies, it appears that the D1, D2, D3, (and perhaps D4) receptor subtypes are involved in the reinforcing effects of cocaine. Selective antagonists for these receptor subtypes might be useful in the treatment of cocaine vs. D1 and D2, may be especially useful. Computational studies are currently underway to aid in the design of selective D3 (and D4) antagonist compounds. We require structural data for as man high-activity D2 and D3 compounds as possible to aid in our molecular modeling studies. This requested starting grant will be used to search x-ray crystallographic databases for that information.
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