The effect of the atypical antipsychotic drug, amperozide, on carrier- mediated striatal dopamine release measured in vivo

BK Yamamoto and HY Meltzer

Department of Psychiatry, Case Western Reserve University, School of Medicine, Cleveland, Ohio.

The effect of the novel atypical antipsychotic drug, amperozide, on carrier-mediated dopamine efflux was studied using in vivo microdialysis in the striatum of awake-behaving rats. Amperozide was infused directly through the dialysis probe. This local infusion produced a concentration-dependent increase in striatal dopamine overflow. This increase was attenuated when a Ca(++)-free perfusion medium was used. Local infusion of amperozide blocked dopamine efflux after the systemic administration of amphetamine in a concentration- dependent manner. The antagonistic effect of amperozide (50 microM) on amphetamine-induced efflux of dopamine was not attenuated under Ca(++)- free conditions. Similar to its effects on amphetamine-induced dopamine efflux, amperozide (50 microM) attenuated the increase in dopamine overflow produced by ouabain (10 microM) but not veratridine (15 microM). The systemic coadministration of amperozide (10 mg/kg, i.p.) and haloperidol (2 mg/kg, i.p.) increased extracellular dopamine levels in an additive manner when compared to the increases observed after the administration of either drug alone. Overall, these data indicate that amperozide acts on the dopamine transporter to inhibit carrier-mediated release.

Volume 263, Issue 1, pp. 180-185, 10/01/1992
Copyright © 1992 by American Society for Pharmacology and Experimental Therapeutics