Human 5HT 1E Serotonin Receptor Drug Development (RMI)

描述（由申请人提供）：5HT1E 5 -羟色胺受体是人类14种5 -羟色胺受体之一。它在人类大脑皮质组织中特别高表达，表明通过药物调节该受体可能对认知和/或情绪产生强大的影响。令人惊讶的是，关于该受体固有功能的信息很少，可能是由于缺乏选择性药物来刺激或拮抗5HT1E受体。为了进一步发展5HT1E受体的药理学研究，我们提出开发一种高通量筛选5HT1E受体选择性激动剂和拮抗剂的方法。本提案的具体目的是证明重组细胞系具有允许使用SPA（闪烁接近测定）的HTS应用于开发这种未被研究的人脑5 -羟色胺受体的新型特异性激动剂和拮抗剂的特性。5HT1E受体的选择性激动剂和拮抗剂至少应该提供有关这种高表达受体功能的信息，并可能导致治疗脑功能障碍的新方法。

DESCRIPTION (provided by applicant): The 5HT1E serotonin receptor is one of fourteen serotonin receptors expressed in humans. It is especially highly expressed in human cortical brain tissue, indicating modulation of this receptor by drugs may produce robust effects on cognition and/or mood. There has been surprisingly little information on the inherent function of this receptor, presumably due to the lack of selective drugs to stimulate or antagonize the 5HT1E receptor. In order to advance the field of 5HT1E receptor pharmacology we propose to develop a high throughput screen (NTS) for selective agonists and antagonists for the human 5HT1E receptor. The specific aims of this proposal are to demonstrate that the recombinant cell line possesses the properties that will allow the application of HTS using SPA (Scintillation Proximity Assays) to the development of novel, specific agonists and antagonists for this understudied human brain serotonin receptor. Selective agonists and antagonists for the 5HT1E receptor should, at the least, provide information on the function of this highly expressed receptor, and may lead to novel therapeutics for brain dysfunction.