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 μmol. An isobolographic analysis indicated that metaphit interacted additively with PCP and pentobarbital. Animals that recovered 24 or 48 hr after a large dose (1 μmol i.c.v.) or metaphit or phenylisothiocyanate, a nonspecific acylating control substance, were then given PCP (18.3 μmol/kg i.p.) or pentobarbital (76.7 μmol/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.