In vitro and in vivo evaluation of cis-methyl-phencyclidine (CIS-MPCP) as a potential antagonist of phencyclidine (PCP).
In four preparations/tests (isolated nerve, ventricular strip, rotarod, and mouse acute lethality), cis-N-phenyl-4-methyl-cyclohexyl piperidine (cis-MPCP) was consistently less active than PCP and trans-MPCP. As expected, cis-MPCP, at 10(-4)M, which did not depress the action potential evoked on frog sciatic nerves, reduced by half both the nerve block and prolongation of relative refractory period caused by PCP. However, cis-MPCP at 10(-6)M, which by itself had little effect, failed to reduce the positive inotropic effect of PCP on the field-stimulated rat ventricular strip. Cis-MPCP also failed to decrease the ataxic effect of 6 mg/kg PCP (ED80) in the mouse rotarod test. Finally, at a dose that was neither ataxic nor lethal to mice (20 mg/kg), cis-MPCP failed to reduce the 24-hour LD50 of PCP. These data suggest that the actions of PCP are mediated through a multiple receptor system.
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D004353:Drug Evaluation, Preclinical; D007700:Kinetics; D007928:Lethal Dose 50; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D009200:Myocardial Contraction / Q000187:drug effects; D010622:Phencyclidine / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors* / Q000494:pharmacology / Q000633:toxicity; D011894:Rana pipiens; D051381:Rats; D011919:Rats, Inbred Strains; D012584:Sciatic Nerve / Q000502:physiology; D016276:Ventricular Function
C034525:1-(1-phenylcyclohexyl)-4-methylpiperidine; D010622:Phencyclidine