MOLECULAR MODELING OF DOPAMINE ANTAGONISTS

可可碱的强化作用被认为与其 抑制多巴胺摄取的能力。 从行为研究来看， 似乎D1，D2，D3（可能还有D4）受体亚型是 与可卡因的强化作用有关 选择性拮抗剂 对于这些受体亚型， 可卡因与D1和D2相比，可能特别有用。 计算 目前正在进行研究，以帮助设计选择性D3 (and D4）拮抗剂化合物。 我们需要人类的结构数据 高活性D2和D3化合物，以帮助我们的分子 建模研究。 申请的启动补助金将用于 在X射线晶体学数据库中搜索这些信息。

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.