Effects of anticholinergic antiparkinsonian drugs on binding of muscarinic receptor subtypes in rat brain.

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.