Pharmacological comparison of muscarinic ligands: Historical versus more recent muscarinic M1-preferring receptor agonists
Pharmacological comparison of muscarinic ligands: Historical versus more recent muscarinic M1-preferring receptor agonists
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DOI：
10.1016/j.ejphar.2008.12.044
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发表时间：
2009-03-01
影响因子：
5
通讯作者：
Mayer, Scott C.
中科院分区：
文献类型：
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作者：
Heinrich, Julia N.;Butera, John A.;Mayer, Scott C.
在使用五种毒蕈碱受体亚型的功能分析评估中，第二代毒蕈碱M-1偏好受体激动剂[AC-42 (1), AC-260584 (2), 77- hh -28-1(3)和LY-593039(4)]与历史激动剂[talsaclidine (8), sabcomeline (10), xanomeline (11), WAY-132983(12)，塞维米林(9)和NGX-267(6)]相比，对毒蕈碱M-1具有更高的选择性。这些新化合物的另一个显著区别是它们对多巴胺D-2和5-HT2B受体的亲和力。综上所述，这些结果表明，与历史上的激动剂相比，新化合物可能具有更高的临床安全性，特别是在毒蕈碱M-3受体介导的事件方面，但它们对其他受体的亲和力仍可能影响它们在验证毒蕈碱M-1受体激动剂治疗潜力方面的应用。(C) 2009 Elsevier B.V.版权所有
In functional assay assessments using the five muscarinic receptor subtypes, a second generation of muscarinic M-1-preferring receptor agonists [AC-42 (1), AC-260584 (2), 77-LH-28-1 (3) and LY-593039 (4)] was shown to have higher selectivity for muscarinic M-1 over M-3 receptor as compared to historical agonists [talsaclidine (8), sabcomeline (10), xanomeline (11), WAY-132983 (12), cevimeline (9) and NGX-267 (6)]. Another striking difference of these more recent compounds is their affinities for the dopamine D-2 and 5-HT2B receptors. Taken together, these results suggest that the newer compounds may have a greater clinical safety profile, especially with regard to muscarinic M-3 receptor-mediated events, than the historical agonists, but their affinities for other receptors may still compromise their use to validate the therapeutic potential of muscarinic M-1 receptor agonists. (C) 2009 Elsevier B.V. All rights reserved.