SINGLE ORAL DOSES OF AMISULPRIDE DO NOT ENHANCE THE EFFECTS OF ALCOHOL ON THE PERFORMANCE AND MEMORY OF HEALTHY-SUBJECTS

Objectives: Amisulpride is a benzamide antipsychotic that binds select ively to dopamine D-2- and D-3-receptors, preferentially in limbic and hippocampal structures. Since other substituted benzamides have a lim ited or negligible interaction with alcohol on human performance, amis ulpride was studied for this potential. Methods: In a randomised doubl e-blind crossover study, 18 young, non-smoking men took single oral do ses of placebo and amisulpride 50 mg and 200 mg, without and with etha nol (0.8 g . kg(-1)) taken 30 min later. Objective performance tests a nd self-ratings were done at baseline and 1.5, 3.5 and 6.5 h after dru g intake. Memory (immediate and delayed recall) was tested 2 h after d osing. Breath ethanol and the plasma concentrations of amisulpride and prolactin were measured. Three-way ANOVA + Newman-Keul tests were use d for statistical analyses; interactions were confirmed by factorial c ontrast ANOVA. Results: Mean blood ethanol was 0.94, 0.62 and 0.26 g . l(-1) at the three test times. It produced significant impairment in all performance tests (symbol digit substitution, simulated driving, b ody sway, flicker fusion, tapping, nystagmus), reduced both immediate and delayed recall in memory tests, and caused subjective clumsiness, muzziness and mental slowness, mainly between 1.5 to 4.5 h after dosin g. Amisulpride, 50 and 200 mg elevated plasma prolactin but had minima l or no effect on performance, attention and memory. The decreases in immediate free recall after the 50 mg dose and in delayed free recall after the 200 mg dose were slight. Amisulpride neither modified blood ethanol concentrations nor enhanced the detrimental effect of ethanol on skilled and cognitive performance; it slightly antagonised ethanol in the digit copying test. Ethanol did not modify the effect of amisul pride on plasma prolactin, and the plasma concentrations of amisulprid e were little changed by ethanol. Conclusions: Amisulpride in single o ral doses of 50 and 200 mg did not interact significantly with the eff ects of high, moderate or low concentrations of ethanol on human skill ed and cognitive performance. The drugs did interact pharmacokinetical ly.