Metaphit, a proposed phencyclidine receptor acylator: disruption of mouse motor behavior and absence of PCP antagonist activity.
Metaphit, a derivative of phencyclidine (PCP) differing by the meta substitution of an isothiocyanate group on the phenyl ring, was given into the lateral cerebral ventricle of mice alone and as a pretreatment to the subsequent i.p. injection of PCP and pentobarbital. Drug effects on motor performance as an index of neurologic impairment were quantified using the mouse platform test. The ED50 of metaphit to disrupt mouse platform behavior 5 min after i.c.v. administration was 0.48 mumol. An isobolographic analysis indicated that metaphit interacted additively with PCP and pentobarbital. Animals that recovered 24 or 48 hr after a large dose (1 mumol i.c.v.) of metaphit or phenylisothiocyanate, a nonspecific acylating control substance, were then given PCP (18.3 mumol/kg i.p.) or pentobarbital (76.7 mumol/kg i.p.). Both agents enhanced PCP-induced failure of mice to climb to the top of the platform. Metaphit also enhanced pentobarbital-induced failure of mice to climb to the top of the platform. No evidence was obtained that metaphit antagonized the behavioral effects of PCP in mice.
Domino
E F
EF
Department of Pharmacology, University of Michigan, Ann Arbor.
Gole
D
D
Koek
W
W
D000818:Animals; D002552:Cerebral Ventricles / Q000187:drug effects / Q000502:physiology*; D007276:Injections, Intraventricular; D017879:Isothiocyanates; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009043:Motor Activity / Q000187:drug effects*; D010424:Pentobarbital / Q000494:pharmacology; D010622:Phencyclidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology*; D017981:Receptors, Neurotransmitter / Q000187:drug effects / Q000502:physiology*; D017478:Receptors, Phencyclidine; D013861:Thiocyanates / Q000494:pharmacology
D017879:Isothiocyanates; D017981:Receptors, Neurotransmitter; D017478:Receptors, Phencyclidine; D013861:Thiocyanates; C005441:phenylisothiocyanate; C044705:metaphit; D010424:Pentobarbital; D010622:Phencyclidine