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.
O'Neill
S K
SK
Division of Basic Medical Sciences, Memorial University of Newfoundland, St. John's, Canada.
Bolger
G T
GT
D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D015220:Calcium Channels; D003292:Convulsants / Q000494:pharmacology*; D003986:Dibenzocycloheptenes / Q000494:pharmacology*; D016291:Dizocilpine Maleate; D004305:Dose-Response Relationship, Drug; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects*; D009543:Nifedipine / Q000493:pharmacokinetics / Q000494:pharmacology*; D010622:Phencyclidine / Q000494:pharmacology*; D011978:Receptors, Nicotinic / Q000187:drug effects / Q000502:physiology; D012640:Seizures / Q000139:chemically induced* / Q000503:physiopathology
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D003292:Convulsants; D003986:Dibenzocycloheptenes; D011978:Receptors, Nicotinic; D016291:Dizocilpine Maleate; D009543:Nifedipine; D010622:Phencyclidine