Phencyclidine and MK-801: a behavioral and neurochemical comparison of their interactions with dihydropyridine calcium antagonists.

The impairment of rotarod ability and the convulsive activity of phencyclidine (PCP) and MK-801 were compared in male CD-1 mice. The putative interaction between nifedipine and PCP and MK-801 on these behavioral measurements was also quantitated and compared. MK-801 produced a dose dependent inhibition of rotarod ability with an ED50 of 0.5 mg/kg. Nifedipine potentiated the impairment of rotarod ability by MK-801. Both PCP and MK-801 produced convulsive behavior in mice which was characterized by jumping and wild running fits; the CD50 for MK-801 was 1.3 mg/kg. Nifedipine dose dependently inhibited the convulsions associated with MK-801 and PCP. PCP but not MK-801 increased [3H]nitrendipine binding to dihydropyridine (DHP) binding sites on mouse brain membranes. MK-801 blocked the effects of PCP on [3H]nitrendipine binding. These findings suggest that MK-801 is a potent PCP-like drug which interacts with nifedipine and neuronal DHP binding sites. Nifedipine's reduction of the hyperactivity and convulsions elicited by MK-801 may be of importance in the eventual development of MK-801 as an antiischaemic and anticonvulsant drug.