二苯基丁基哌啶类抗精神分裂症药物作为钙通道拮抗剂发挥作用。
Antischizophrenic drugs of the diphenylbutylpiperidine type act as calcium channel antagonists.
作者信息
Gould R J, Murphy K M, Reynolds I J, Snyder S H
出版信息
Proc Natl Acad Sci U S A. 1983 Aug;80(16):5122-5. doi: 10.1073/pnas.80.16.5122.
Abstract
Antischizophrenic neuroleptic drugs of the diphenylbutylpiperidine class, which includes pimozide, fluspirilene, penfluridol, and clopimozide, inhibit [3H]nitrendipine binding with IC50 values of 13-30 nM. This inhibition involves receptors for the verapamil/prenylamine class of calcium channel antagonists. These diphenylbutylpiperidines also inhibit potassium-induced calcium-dependent contractions of rat vas deferens at concentrations of 40-350 nM. Other phenothiazine and butyrophenone neuroleptics lack such potent calcium-antagonist actions. Diphenylbutylpiperidines also differ from other neuroleptics in their ability to relieve negative symptoms of schizophrenia, such as emotional withdrawal, as well as the positive symptoms which respond to all neuroleptics. We suggest that these unique antischizophrenic actions are related to a blockade by diphenylbutylpiperidines of voltage-operated calcium channels.
摘要
二苯基丁基哌啶类抗精神分裂症的神经安定药物，包括匹莫齐特、氟司必林、五氟利多和氯哌莫齐，抑制[3H]尼群地平结合，IC50值为13 - 30 nM。这种抑制作用涉及维拉帕米/普尼拉明类钙通道拮抗剂的受体。这些二苯基丁基哌啶在浓度为40 - 350 nM时也能抑制大鼠输精管钾诱导的钙依赖性收缩。其他吩噻嗪类和丁酰苯类神经安定药缺乏这种强效的钙拮抗剂作用。二苯基丁基哌啶在缓解精神分裂症阴性症状（如情感退缩）以及对所有神经安定药都有反应的阳性症状方面也与其他神经安定药不同。我们认为这些独特的抗精神分裂症作用与二苯基丁基哌啶对电压门控钙通道的阻断有关。
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本文引用的文献
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The binding of [3H]nitrendipine to receptors for calcium channel antagonists in the heart, cerebral cortex, and ileum of rats.[3H]尼群地平与大鼠心脏、大脑皮层及回肠中钙通道拮抗剂受体的结合。
Life Sci. 1982 Jun 21;30(25):2191-202. doi: 10.1016/0024-3205(82)90293-4.
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Pimozide versus Haloperidol in acute schizophrenia. A double blind controlled study.匹莫齐特与氟哌啶醇治疗急性精神分裂症的双盲对照研究。
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