1,2,5-Thiadiazole derivatives of arecoline stimulate M1 receptors coupled to phosphoinositide turnover.
1,2,5-Thiadiazole derivatives of arecoline stimulate M1 receptors coupled to phosphoinositide turnover.
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槟榔碱的 1,2,5-噻二唑衍生物刺激与磷酸肌醇转换相关的 M1 受体。
DOI：
10.1016/0006-8993(95)00724-5
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发表时间：
1995
期刊：
影响因子：
2.9
通讯作者：
Hoss,W
中科院分区：
文献类型：
--
作者：
Periyasamy,S;MesserJr,WS;Roknich,S;Sauerberg,P;Hoss,W
为了开发M1毒蕈碱受体激动剂，合成了一系列槟榔碱烷氧基-1，2，5-噻二唑衍生物。3-丁烯氧基，2-丁炔氧基，环丙基甲氧基，和己氧基衍生物刺激磷酸肌醇营业额通过毒蕈碱受体在大鼠海马。与槟榔碱相比，2-丁炔氧基、环丙基甲氧基和己氧基化合物的剂量-反应曲线被发现是双相的。槟榔碱和己氧基化合物一起的最大PI周转响应与各自单独的响应相同。哌仑西平在抑制低浓度噻二唑衍生物产生的反应方面比AF-DX 116更有效。这些数据表明，环丙基甲氧基-TZTP衍生物是功能上的选择性M1激动剂。分子力学计算表明，槟榔碱的1，2，5-噻二唑衍生物的反式可能对M1受体有活性。
A series of alkoxy-1,2,5-thiadiazole derivatives of arecoline was synthesized in an effort develop M1muscarinic agonists. The 3-butenyloxy, 2-butynyloxy, cyclopropylmethyloxy, and hexyloxy derivatives stimulated phosphoinositide turnover through muscarinic receptors in the rat hippocampus. The dose-response curves of 2-butynyloxy, cyclopropylmethyloxy and hexyloxy compounds were found to be biphasic compared to arecoline. The maximal PI turnover response of arecoline and the hexyloxy compound together was the same as the response of each separately. Pirenzepine was somewhat more potent than AF-DX 116 for inhibiting the responses produced by low concentrations of the thiadiazole derivatives. The data suggest that the cyclopropylmethyloxy-TZTP derivative is functionally a selective M1agonist. Molecular mechanics calculations indicate that the anti form of the 1,2,5-thiadiazole derivatives of arecoline may be active at M1receptors.