COMPARISON OF THE EFFECT OF SUBSTITUTED BENZAMIDES ON MIDBRAIN DOPAMINE NEURONS AFTER TREATMENT OF RATS FOR 21 DAYS

We have tested five different substituted benzamides (nemonapride, D,L -sulpiride, remoxipride, raclopride and zacopride) for their potential to decrease the number of spontaneously active dopamine neurones in t he rat midbrain after treatment for 21 days. Nemonapride, D,L-sulpirid e, and remoxipride significantly reduced the number of spontaneously a ctive dopamine neurones in the ventral tegmental area, indicating an a ntipsychotic potential, while raclopride and zacopride induced but min or effects. The number of active dopamine neurones in the substantia n igra pars compacta was reduced by nemonapride at higher doses which sh ould indicate the propensity for developing extrapyramidal side-effect s. In conclusion, several of the substituted benzamides showed an anti psychotic profile in this test model. In addition, some of the benzami des also showed,a propensity for extrapyramidal side-effects and these results are in accordance with the profile reported from clinical tri als. However, the results obtained with this model indicate that raclo pride neither has antipsychotic potential nor induces extrapyramidal s ide-effects. The reason for this discrepancy is at present not known.