Potential benefits of muscarinic M3 receptor selectivity
Potential benefits of muscarinic M3 receptor selectivity
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DOI：
10.1016/s1569-9056(02)00045-3
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发表时间：
2002-07-01
影响因子：
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通讯作者：
Andersson, KE
中科院分区：
文献类型：
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作者：
Andersson, KE
逼尿肌含有M-2（约2/3）和M-3（约1/3）亚型的毒蕈碱受体。M-3受体主要负责正常的排尿收缩，而M-2受体的作用尚未阐明。在某些疾病状态下，M-2受体也可能有助于膀胱收缩。不同的毒蕈碱受体亚型可以促进细胞活化或抑制的过程。例如，在唾液腺中，M-1和M-3受体亚型都可以控制分泌。在心血管系统中，M-2受体亚型可介导副交感神经驱动的心动过缓和心输出量减少。在大脑中，皮层M1受体在认知中的作用已被充分证明，M1受体阻断剂将被预期损害中枢神经系统功能。介导人睫状肌收缩的毒蕈碱受体最可能是M-3和M-5。对M-3受体具有选择性的药物可能预期对逼尿肌过度活动具有临床疗效，并减少与阻断其他受体亚型相关的不良事件。然而，药物的临床有效性不仅取决于其受体亲和力，还取决于其药代动力学和特定毒蕈碱受体对给定器官功能的重要性。(C)2002 Elsevier Science B. V.保留所有权利。
Detrusor smooth muscle contains muscarinic receptors of the M-2 (approximate to2/3) and M-3 (approximate to1/3) subtypes. M-3 receptors are mainly responsible for normal micturition contraction, whereas, the role Of M-2 receptors has not yet been clarified. In certain disease states, M-2 receptors may also contribute to bladder contraction. Different muscarinic receptor subtypes can contribute to processes of cellular activation or inhibition. For example, in salivary glands, both M-1 and M-3 receptor subtypes may control secretion. In the cardiovascular system, the M-2 receptor subtype can mediate parasympathetically-driven bradycardia and a decrease in cardiac output. In the brain, where the role of cortical M, receptors in cognition is well documented, M-1 receptor blockade would be expected to compromise central nervous system function. Muscarinic receptors that mediate contraction of human ciliary muscle are most probably M-3 and M-5. Drugs selective for the M-3 receptor might be expected to have clinical efficacy in detrusor overactivity with a reduction in adverse events related to the blockade of other receptor subtypes. However, the clinical effectiveness of a drug depends not only on its receptor affinity, but also on its pharmacokinetics and the importance of specific muscarinic receptors for a given organ function. (C) 2002 Elsevier Science B.V. All rights reserved.