Katayama S, Ishizaki F, Yamamura Y, Khoriyama T, Kito S
Third Department of Internal Medicine, Hiroshima University School of Medicine, Japan.
Res Commun Chem Pathol Pharmacol. 1990 Sep;69(3):261-70.
Anticholinergic antiparkinsonian drugs have been widely used for the treatment of extrapyramidal disorders for a long time although their pharmacological characterization has been unclear. We studied the rank of potency of the effects of anticholinergic antiparkinsonian drugs to binding of 3H-QNB and 3H-PZ and calculated the affinity of each drug to the M1 receptor. All the drugs were potent inhibitors of 3H-QNB and 3H-PZ binding. The order of potency for 3H-QNB being: mazaticol greater than atropine greater than piroheptine greater than trihexyphenidyl greater than biperiden greater than ethopropazine greater than pirenzepine. The order of potency for 3H-PZ being: mazaticol greater than atropine greater than trihexyphenidyl greater than biperiden greater than ethopropazine greater than pirenzepine. Ki ratio indicated that trihexiphenidyl and biperiden bound to the M1 receptors selectively with high affinity and mazaticol would bind to the M2 receptors with higher affinity than atropine. These data suggest that we may be able to consider the pathophysiology of some extrapyramidal disorders based on the therapeutic efficacy of anticholinergic drugs which selectively affect M1 or M2 receptors.
抗胆碱能抗帕金森病药物长期以来一直广泛用于治疗锥体外系疾病，尽管其药理学特性尚不清楚。我们研究了抗胆碱能抗帕金森病药物对3H-QNB和3H-PZ结合作用的效价顺序，并计算了每种药物对M1受体的亲和力。所有药物都是3H-QNB和3H-PZ结合的有效抑制剂。3H-QNB的效价顺序为：马扎替考大于阿托品大于匹罗卡品大于苯海索大于安克痉大于乙丙嗪大于哌仑西平。3H-PZ的效价顺序为：马扎替考大于阿托品大于苯海索大于安克痉大于乙丙嗪大于哌仑西平。Ki比值表明，苯海索和安克痉以高亲和力选择性地与M1受体结合，而马扎替考与M2受体结合的亲和力高于阿托品。这些数据表明，我们或许能够根据选择性作用于M1或M2受体的抗胆碱能药物的治疗效果来考虑某些锥体外系疾病的病理生理学。
