Antagonistic Effects of OPC-14597, a Novel Antipsychotic Drug, on Quinpirole- and (–)-Sulpiride-induced Changes in Evoked Dopamine Release in Rat Striatal Slices

The effects of a newly synthesized quinolinone derivative, 7-[4-(4-(2,3-dichlorophenyl)-1-piperazinyl) butoxy)-3,4-dihydro-2-(1H)-quinolinone (OPC-14597), a novel antipsychotic drug, on electrically evoked dopamine release in rat striatal slices were investigated. OPC-14597 (0.1-10 microM) had no effect on the dopamine release evoked in the striatal slices. The decrease induced by quinpirole, a dopamine receptor agonist, in evoked dopamine release was attenuated by superfusion with OPC-14597 (1 and 10 microM) which by itself had no effect on evoked dopamine release. The increase induced by (-)-sulpiride, a dopamine receptor antagonist, in evoked dopamine release was, moreover, also attenuated by 1 and 10 microM OPC-14597. These findings indicate that OPC-14597 antagonizes both dopamine agonist- and antagonist-induced changes in evoked dopamine release in striatal slices in rats.