J. Semba et al., BEHAVIORAL AND NEUROCHEMICAL EFFECTS OF OPC-14597, A NOVEL ANTIPSYCHOTIC DRUG, ON DOPAMINERGIC MECHANISMS IN RAT-BRAIN, Neuropharmacology, 34(7), 1995, pp. 785-791
OPC-14597 is a new antipsychotic drug with a unique pharmacological pr
ofile. In a behavioural study in rats OPC-14597 did not show catalepto
genic activity even at the highest dose (40 mg/kg, i.p.), whereas it a
ntagonized 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 administratio
n 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 m
g/kg. Similar results were obtained in extracellular dopamine concentr
ation in the frontal cortex, although the changes in DOPAC and HVA con
centrations were smaller than those in the striatum. OPC-14597 also an
tagonized DA increase induced by the DA autoreceptor antagonist (+)-AJ
76. These results suggest that OPC-14597 acts either as an antagonist
at postsynaptic dopamine receptors or as an agonist at presynaptic dop
amine autoreceptors.