新型II组代谢型谷氨酸受体激动剂LY379268的临床前特性。
The preclinical properties of a novel group II metabotropic glutamate receptor agonist LY379268.
作者信息
Imre Gabor
机构信息
Department of Behavioral Pharmacology, Gedeon Richter Ltd., Budapest, Hungary.
出版信息
CNS Drug Rev. 2007 Winter;13(4):444-64. doi: 10.1111/j.1527-3458.2007.00024.x.
Abstract
Activation of group II metabotropic glutamate (mGlu2/3) receptors reduces excessive glutamate release that is often associated with neurodegenerative and psychiatric disorders. This finding encouraged the search for potent and selective agonists as potential therapeutic agents. The search led to the discovery of LY379268 {(-)-2-oxa-4-aminobicyclo[3.1.0]hexane-4,6-dicarboxylic acid}, which is a highly potent and systemically available mGlu2/3 receptor agonist. LY379268 was effective in several animal models of stroke, epilepsy, drug abuse, schizophrenia, and pain. Suppression of motor activity is the major side effect of LY379268. Upon repeated administration tolerance develops to this side effect, while the therapeutic effects of LY379268 remain. To date, no clinical data with LY379268 are available. This review article summarizes the preclinical pharmacology of LY379268.
摘要
II 型代谢型谷氨酸（mGlu2/3）受体的激活可减少通常与神经退行性疾病和精神疾病相关的过量谷氨酸释放。这一发现促使人们寻找强效且选择性的激动剂作为潜在治疗药物。这一探索导致了LY379268 {(-)-2-氧杂-4-氨基双环[3.1.0]己烷-4,6-二甲酸} 的发现，它是一种高效且可全身应用的 mGlu2/3 受体激动剂。LY379268 在中风、癫痫、药物滥用、精神分裂症和疼痛的多种动物模型中均有效。运动活动抑制是 LY379268 的主要副作用。反复给药后会对这种副作用产生耐受性，而 LY379268 的治疗效果依然存在。迄今为止，尚无关于 LY379268 的临床数据。这篇综述文章总结了 LY379268 的临床前药理学。
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