BEHAVIORAL AND NEUROCHEMICAL EFFECTS OF OPC-14597, A NOVEL ANTIPSYCHOTIC DRUG, ON DOPAMINERGIC MECHANISMS IN RAT-BRAIN

OPC-14597 is a new antipsychotic drug with a unique pharmacological profile. In a behavioural study in rats OPC-14597 did not show cataleptogenic activity even at the highest dose (40 mg/kg, i.p.), whereas it antagonized apomorphine-induced stereotypy dose-dependently (0.5-40 mg/kg). In vivo microdialysis showed that extracellular dopamine (DA) in the striatum was decreased significantly after OPC-14597 administration at the higher doses of 10 and 40 mg/kg. DOPAC and HVA were increased at low doses (2.5 and 10 mg/kg) but returned to control level at 40 mg/kg. Similar results were obtained in extracellular dopamine concentration in the frontal cortex, although the changes in DOPAC and HVA concentrations were smaller than those in the striatum. OPC-14597 also antagonized DA increase induced by the DA autoreceptor antagonist (+)-AJ76. These results suggest that OPC-14597 acts either as an antagonist at postsynaptic dopamine receptors or as an agonist at presynaptic dopamine autoreceptors.