Elucidating the role of muscarinic receptors in psychosis
Elucidating the role of muscarinic receptors in psychosis
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DOI：
10.1016/s0024-3205(01)01059-1
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发表时间：
2001-04-27
期刊：
影响因子：
6.1
通讯作者：
Wess, J
中科院分区：
文献类型：
--
作者：
Felder, CC;Porter, AC;Wess, J
基于来自临床前和临床研究的药理学证据，毒蕈碱受体已经涉及认知和精神病的调节。毒蕈碱激动剂在临床上已显示出改善认知和减少阿尔茨海默病患者精神病发作的前景。然而，由于在较高剂量下观察到的麻烦的副作用，缺乏选择性毒蕈碱配体限制了它们的使用。如果没有选择性配体，很难将特定的毒蕈碱受体亚型分配给这些高级心理过程。毒蕈碱受体敲除小鼠的最新发展为在行为测定中研究认知和精神病以及确定与拟副交感神经生理学相关的受体亚型提供了额外的工具。生物化学研究表明，M-1受体在调节海马和皮质中G α介导的信号转导中起重要作用。行为研究表明，M-4受体参与运动调节和惊吓反射的前脉冲抑制，这是一种注意力的测量。这些发现支持了M-1和M-4受体激动剂在开发用于症状包括认知障碍和精神病行为的疾病中的作用。(C)2001 Elsevier Science Inc. All rights reserved.
Muscarinic receptors have been implicated in the regulation of cognition and psychosis based on pharmacological evidence from pre-clinical and clinical studies. Muscarinic agonists have shown promise in the clinic in improving cognition and reducing psychotic episodes in Alzheimer's patients. However, lack of selective muscarinic ligands has limited their use due to troublesome side effects observed at higher doses. Without selective ligands, it has been difficult to assign a specific muscarinic receptor subtype to these high order mental processes. Recent development of muscarinic receptor knockout mice has provided additional tools to investigate cognition and psychosis in behavioral assays and to determine the receptor subtypes associated with parasympathomimetic physiology. Biochemical studies indicate that the M-1 receptor plays a significant role in regulating G alphaq-mediated signal transduction in the hippocampus and cortex. Behavioral studies suggest that the M-4 receptor is involved in movement regulation and prepulse inhibition of the startle reflex, a measure of attention. These findings support a role for the development of M-1 and M-4 receptor agonists for diseases in which symptoms include cognitive impairment and psychotic behaviors. (C) 2001 Elsevier Science Inc. All rights reserved.