Development of the strategy for the quantitative prediction and avoidance of drug-induced Parkinsonism based on pharmacokinetics and pharmacodynamics

1)研究了25种药物对吗啡D_1、D_2和M胆碱受体的毒性强度和体内受体的占有率。根据这些受体的出现，可以预测惊厥的强度。ii)研究结构与药物诱导的帕金森病之间的关系。二乙氨基甲基部分被发现在帕金森病的诱发中起重要作用。4)体外实验评估了25种药物对药物诱导帕金森综合征的定量预测所必需的多巴胺D_1、D_2和M胆碱受体的亲和力。v)利用上述研究结果，开发了用于人类药物诱导帕金森反应定量预测的策略。

i) The intensity of catalepsy and in vivo receptor occupancies for domapine D1, D2 and muscarinic acetylcholine receptors were investigated for 25 drugs in mice. The intensity of catalepsy was found to be predictable from these receptor occupancies.ii) The relationship between structure and drug-induced parkinsonism was investigated. The diethylaminomethyl moiety was found to play an important role in the induction of parkinsonism.iii) A case of propiverine-induced parkinsonism was found. The mechanisms underlying the induction of parkinsonism by propiverine was investigated in mice.iv) In vitro experiments were carried out to estimate the affinities of 25 drugs for dopamine D1, D2 and muscarinic acetylcholine receptors, which were indispensable for quantitative prediction of drug-induced parkinsonism.v) Developed was the strategy for the quantitative prediction of drug-induced parkinsonism in humans using the above results of i) and iv).vi) The above(iv) strategy was applied to develop a computer-aided drug information system for rational prescription.