Behavioural 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 higher doses of 10 and 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 that OPC-14597 acts either as an antagonist at postsynaptic dopamine receptors or as an agonist at presynaptic dopamine autoreceptors.
Semba
J
J
Division of Health Sciences, University of the Air, Chiba, Japan.
Watanabe
A
A
Kito
S
S
Toru
M
M
D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D000068180:Aripiprazole; D017660:Autoreceptors / Q000187:drug effects; D001522:Behavior, Animal / Q000187:drug effects*; D001921:Brain / Q000187:drug effects*; D004298:Dopamine / Q000378:metabolism*; D006220:Haloperidol / Q000494:pharmacology; D008297:Male; D017551:Microdialysis; D009474:Neurons / Q000187:drug effects; D010879:Piperazines / Q000494:pharmacology*; D015363:Quinolones / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D014150:Antipsychotic Agents; D017660:Autoreceptors; D010879:Piperazines; D015363:Quinolones; D000068180:Aripiprazole; D006220:Haloperidol; D004298:Dopamine