Cardioselective profile of AF-DX 116, a muscarine M2 receptor antagonist.
Cardioselective profile of AF-DX 116, a muscarine M2 receptor antagonist.
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AF-DX 116（一种毒蕈碱 M2 受体拮抗剂）的心脏选择性特征。
DOI：
10.1016/0024-3205(86)90410-8
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发表时间：
1986
期刊：
影响因子：
6.1
通讯作者：
E. Montagna
中科院分区：
文献类型：
--
作者：
A. Giachetti;R. Micheletti;E. Montagna
AF-DX 116（化学名称见下文）是外周器官中肌碱受体的竞争性拮抗剂。与吡仑西平相反，它在功能实验中的行为表明对M2muscarinic亚型有选择性。在灌胃大鼠中，AF-DX 116抑制迷走神经诱导的心动过缓，表现为m2反应（ED5032 μg/kg i.v），优于m1介导的McN-A-343的降压反应（ED50211 μg/kg i.v）。AF-DX 116进一步区分m2受体，显示出对心肌肌碱受体的高亲和力。在分离制剂中，AF-DX 116对心脏肌碱受体（pA27.33）的亲和力比对平滑肌受体（pA26.39−6.44）的亲和力高10倍。动物研究中也出现了同样的情况，与血管、平滑肌或分泌反应相比，该化合物是内源性或外源性激活的心脏肌碱反应的更有效拮抗剂。一般来说，在心脏和其他肌碱介导的功能中观察到的效价（ED50）之比在30到50之间。在相同剂量范围内，阿托品对所有毒蕈碱反应均无明显的抑制作用。在清醒的狗体内静脉注射AF-DX 116增加了基础心率，并完全逆转了可乐定引起的反射性心动过缓。心动过速与剂量相关（ED5079 μg/kg静脉注射），与背景交感神经张力无关。AF-DX 116清楚区分M1和m2介导的反应；它还强调了长期以来公认的外周m2亚型之间的异质性。AF-DX 116因其明显的心脏选择性，可能在治疗窦性心动过缓方面具有治疗潜力。
AF-DX 116 (see chemical name below) is a competitive antagonist of muscarine receptors in peripheral organs. In contrast to pirenzepine, its behaviour in functional experiments indicates selectivity for the M2muscarinic subtype. In pithed rats AF-DX 116 inhibits vagally-induced bradycardia, an M2response, (ED5032 μg/kg i.v.) in preference to the M1-mediated pressor response to McN-A-343 (ED50211 μg/kg i.v.). AF-DX 116 further discriminates among M2receptors, showing a high affinity for the cardiac muscarine receptors. In isolated preparations, AF-DX 116 has a tenfold higher affinity for the muscarine receptors of the heart (pA27.33) than for those in smooth muscles (pA26.39 −6.44). The same profile appears from animal studies, where the compound is a more potent antagonist of either endogenously or exogenously activated cardiac muscarine responses as compared to vascular, smooth muscle or secretory responses. In general, the ratios of potencies (ED50) observed in cardiac vs. other muscarine mediated functions ranged between 30 and 50. Atropine showed no discrimination, inhibiting all muscarine responses in the same range of doses. In the conscious dog intravenuos AF-DX 116 increased basal heart rate, and completely reversed the reflex bradycardia induced by clonidine. Tachycardia was dose-related (ED5079 μg/kg i.v.), and occurred independently of background sympathetic tone. AF-DX 116 clearly distinguishes between M1- and M2-mediated responses; it also emphasizes the long-recognized heterogeneity among the peripheral M2subtypes. AF-DX 116, for its pronounced cardioselectivity, may have a therapeutic potential in the treatment of sinus bradycardia.
[3H]哌仑西平和[3H]奎宁环苯苯甲酸与大鼠脑中毒蕈碱胆碱能受体结合的比较。
DOI：
--
发表时间：
1984
期刊：
The Journal of pharmacology and experimental therapeutics
影响因子：
--
作者：
Luthin,GR;Wolfe,BB
通讯作者：
Wolfe,BB
哌仑西平区分毒蕈碱受体介导的磷酸肌醇分解和腺苷酸环化酶抑制。
DOI：
--
发表时间：
1985
期刊：
The Journal of pharmacology and experimental therapeutics
影响因子：
--
作者：
Gil,DW;Wolfe,BB
通讯作者：
Wolfe,BB
[3h]pirenzepine 选择性识别大鼠大脑皮层中毒蕈碱胆碱能受体的高亲和力群体。
影响因子：
6.1
作者：
Watson,M;Roeske,WR;Yamamura,HI
通讯作者：
Yamamura,HI