Chlorpromazine and its metabolites alter polymerization and gelation of actin.
Chlorpromazine and its metabolites alter polymerization and gelation of actin.
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氯丙嗪及其代谢物改变肌动蛋白的聚合和凝胶化。
DOI：
10.1126/science.574316
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发表时间：
1979
期刊：
影响因子：
56.9
通讯作者：
J. Boyer
中科院分区：
文献类型：
--
作者：
E. Elias;J. Boyer
氯丙嗪（10（-5）M至10（-4）M）是一种常用的吩噻嗪类镇静剂，其肝脏羟基化代谢物可与丝状肌动蛋白形成固体凝胶，但毒性较小的氯丙嗪亚砜代谢物则不能。在较高浓度（5 × 10（-4）M）时，氯丙嗪抑制肌动蛋白聚合。这些剂量-反应关系平行的药物在体内的肝毒性，并建议氯丙嗪或氯丙嗪代谢产物和肌动蛋白之间的相互作用可能是细胞损伤的潜在机制。
Hepatic hydroxylated metabolites of chlorpromazine (10(-5)M to 10(-4)M), a frequently used phenothiazine tranquilizer, produce solid gel formation with filamentous actin, but the less toxic chlorpromazine sulfoxide metabolite does not. At higher concentrations (5 x 10(-4)M) chlorpromazine inhibits actin polymerization. These dose-response relationships parallel the drug's hepatic toxicity in vivo and suggest that interactions between chloropromazine or chlorpromazine metabolites and actin could be an underlying mechanism of cell injury.