Antagonism of phencyclidine action by metaphit in rat cerebellar Purkinje neurons: an electrophysiological study

Abstract

Metaphit (1-[1-(3-isothiocyanatophenyl)-cyclohexyl]piperidine), a derivative of the psychotomimetic drug phencyclidine (PCP), is postulated to bind irreversibly to PCP receptors. We examined here the electrophysiological interactions of metaphit with PCP in rat cerebellar cortex, since a specific effect of PCP on cerebellar neuronal circuitry has been shown. Metaphit, applied locally to Purkinje neurons by micropressure ejection through multibarreled micropipettes, has a reversible depressant action lasting for 5-20 min. Following this, PCP-induced inhibition is blocked with no recovery despite repeated applications of PCP for over an hour. This blockade was not seen unless the dose of metaphit was sufficient to transiently depress Purkinje neuron discharge. Metaphit does not antagonize inhibitory effects of locally applied norepinephrine or gamma-aminobutyric acid. This electrophysiological data suggests that metaphit is an irreversible antagonist of PCP in the cerebellum.