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用于治疗帕金森病的胆碱受体拮抗剂对纹状体毒蕈碱受体的拮抗作用，抑制多巴胺D1受体刺激的腺苷酸环化酶活性。

Antagonism of striatal muscarinic receptors inhibiting dopamine D1 receptor-stimulated adenylyl cyclase activity by cholinoceptor antagonist used to treat Parkinson's disease.

作者信息

Olianas M C, Onali P

机构信息

Department of Neurosciences, University of Cagliari, Italy.

出版信息

Br J Pharmacol. 1996 Jun;118(4):827-8. doi: 10.1111/j.1476-5381.1996.tb15474.x.

DOI:10.1111/j.1476-5381.1996.tb15474.x
PMID:8799550
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC1909524/
Abstract

A number of cholinoceptor antagonists used in the treatment of Parkinson's disease were examined for their ability to antagonize either the muscarinic receptor-mediated inhibition of dopamine D1 receptor-stimulated adenylyl cyclase or the muscarinic receptor-mediated stimulation of [3H]-inositol phosphates ([3H]-IPs) formation in rat striatal membranes. The drugs were found to block the receptors inhibiting adenylyl cyclase activation with high affinity and more potently than those stimulating [3H]-IPs formation. Moreover, their rank order of potencies for the former effect showed good correlation with their clinical efficacies. These data suggest that the blockade of the muscarinic receptor-mediated inhibition of striatal dopamine D1 receptor activation may be one of the mechanisms by which cholinoceptor blocking drugs exert their antiparkinsonian effect.

摘要

对一些用于治疗帕金森病的胆碱受体拮抗剂进行了研究，考察它们拮抗毒蕈碱受体介导的对多巴胺D1受体刺激的腺苷酸环化酶的抑制作用，或拮抗毒蕈碱受体介导的大鼠纹状体膜中[3H]-肌醇磷酸酯（[3H]-IPs）生成的刺激作用的能力。发现这些药物以高亲和力阻断抑制腺苷酸环化酶激活的受体，且比阻断刺激[3H]-IPs生成的受体更有效。此外，它们对前一种效应的效价顺序与其临床疗效显示出良好的相关性。这些数据表明，阻断毒蕈碱受体介导的对纹状体多巴胺D1受体激活的抑制作用可能是胆碱受体阻断药物发挥抗帕金森病作用的机制之一。

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Antagonism by antimuscarinic and neuroleptic compounds at the five cloned human muscarinic cholinergic receptors expressed in Chinese hamster ovary cells.抗毒蕈碱和抗精神病化合物对中国仓鼠卵巢细胞中表达的五种克隆人毒蕈碱胆碱能受体的拮抗作用。
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