Antagonists at Metabotropic Glutamate Receptor Subtype 5 Structure Activity Relationships and Therapeutic Potential for Addiction
Antagonists at Metabotropic Glutamate Receptor Subtype 5 Structure Activity Relationships and Therapeutic Potential for Addiction
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DOI：
10.1196/annals.1441.015
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发表时间：
2008-01-01
期刊：
影响因子：
--
通讯作者：
Carroll, F. Ivy
中科院分区：
文献类型：
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作者：
Carroll, F. Ivy
作为深入研究的结果，特别是在制药工业中，已经发现了许多有效的和选择性的代谢型谷氨酸受体亚型5（mGluR5）拮抗剂。本文综述了导致这些mGluR5拮抗剂发现的构效关系研究。在模拟药物奖励、强化和复发的动物模型中对选定的mGluR5拮抗剂进行的研究结果似乎很有希望。药物滥用与焦虑和抑郁症之间的共病性使得药物在这些疾病中的作用引起了极大的兴趣。临床研究表明，mGluR5拮抗剂非诺班是一种有效的抗焦虑药物。几种新的mGluR5拮抗剂在这些疾病的动物模型中产生抗焦虑和抗抑郁样作用。临床和动物研究的结果为寻找机制上不同的药物疗法的新方法提供了信息，以帮助患者实现并保持对可卡因、甲基苯丙胺、阿片类药物、乙醇和尼古丁（吸烟）的戒断。
As a result of intensive investigation, particularly in the pharmaceutical industry, a number of potent and selective metabotropic glutamate receptor subtype 5 (mGluR5) antagonists have been discovered. The structure activity relationship studies that led to the discovery of these mGluR5 antagonists are presented in this review. Results from studies on selected mGluR5 antagonists in animal models that simulate drug reward, reinforcement, and relapse appear promising. The comorbidity between drug abuse and anxiety and depression make drugs active in these disorders of great interest. Clinical studies showed that the mGluR5 antagonist fenobam was an active anxiolytic drug. Several new mGluR5 antagonists produced anxiolytic and antidepressant-like effects in animal models of these disorders. The results from the clinical and animal studies provide information for new approaches to finding mechanistically distinct pharmacotherapies to help patients achieve and maintain abstinence from cocaine, methamphetamine, opiates, ethanol, and nicotine (smoking).