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钙通道阻滞剂在小鼠中诱发的僵住症。

Catalepsy induced by calcium channel blockers in mice.

作者信息

Haraguchi K, Ito K, Kotaki H, Sawada Y, Iga T

机构信息

Department of Pharmacy, University of Tokyo Hospital, Faculty of Medicine, Japan.

出版信息

Biopharm Drug Dispos. 1998 Mar;19(2):115-22. doi: 10.1002/(sici)1099-081x(199803)19:2<115::aid-bdd86>3.0.co;2-q.

Abstract

It is known that calcium channel blockers induce Parkinsonism. In this study, amlodipine-, diltiazem-, and verapamil-induced catalepsy was investigated in mice. All of these three calcium channel blockers induced catalepsy. Dopamine D1, D2, and mACh receptor occupancies were estimated under the same conditions, and the affinities of these drugs for each receptor were also estimated in vitro. Intensity of catalepsy was predicted by dopamine D1, D2, and mACh receptor occupancies with the dynamic model which had already been constructed and was compared with the observed values. The predicted and the observed values were comparable (r = 0.98, p < 0.001). In conclusion, the dynamic model considering D1, and D2, and mACh receptor occupancy may be useful for quantitative prediction of drug-induced catalepsy.

摘要

已知钙通道阻滞剂可诱发帕金森症。在本研究中,对小鼠进行了氨氯地平、地尔硫䓬和维拉帕米诱发的僵住症研究。这三种钙通道阻滞剂均可诱发僵住症。在相同条件下估算多巴胺D1、D2和毒蕈碱型乙酰胆碱(mACh)受体占有率,并在体外评估这些药物对每种受体的亲和力。利用已构建的动力学模型,通过多巴胺D1、D2和mACh受体占有率预测僵住症强度,并与观测值进行比较。预测值与观测值具有可比性(r = 0.98,p < 0.001)。总之,考虑D1、D2和mACh受体占有率的动力学模型可能有助于药物诱发僵住症的定量预测。

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