CATALEPSY INDUCED BY CALCIUM-CHANNEL BLOCKERS IN MICE

It is known that calcium channel blockers induce Parkinsonism. In this study, amlodipine-, diltiazem-, and verayamil-induced catalepsy was i nvestigated in mice. All of these three calcium channel blockers induc ed catalepsy. Dopamine D-1, D-2, and mACh receptor occupancies were es timated under the same conditions, and the affinities of these drugs f or each receptor were also estimated in vitro. Intensity of catalepsy was predicted by dopamine D-1, D-2, 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 con sidering D-1, and D-2, and mACh receptor occupancy may be useful for q uantitative prediction of drug-induced catalepsy. (C) 1998 John Wiley & Sons, Ltd.