AMPEROZIDE, A PUTATIVE ANTIPSYCHOTIC DRUG - UPTAKE INHIBITION AND RELEASE OF DOPAMINE INVITRO IN THE RAT-BRAIN

The effects of amperozide (a diphenylbutylpiperazinecarboxamide derivative) on the uptake and release of 3H-dopamine in vitro were investigated. Amperozide inhibited the amphetamine-stimulated release of dopamine from perfused rat striatal tissue in a dose-dependent manner. With 1 and 10 μm amperozide there was significant inhibition of the amphetamine-stimulated release of dopamine, to 44 and 36 % of control. In contrast, 10 μM amperozide significantly strengthened the electrically stimulated release of dopamine from perfused striatal slices. Amperozide 1-10 μM had no significant effect on the potassium-stimulated release of dopamine, 10 μM amperozide also slightly increased the basal release of 3H-dopamine from perfused striatal tissue. These effects on various types of release are similar to those reported for uptake inhibitors (Bowyer et al, 1984). The uptake of dopamine in striatal tissue was inhibited by amperozide with IC50 values of 18 μM for uptake in chopped tissue and 1.0 μM for uptake in synaptosomes. Amperozide also inhibited the uptake of serotonin in synaptosomes from frontal cortex, IC50 = 0.32 μM and the uptake of noradrenaline in cortical synaptosomes, IC50 = 0.78 μM. In conclusio, amperozide shows uptake-inhibiting properties in both release and uptake studies done in vitro on the rat. In the in vivo studies, however, amperozide differs from dopamine uptake inhibitors. © 1990.