The effect of quipazine on brain monoamines and the significance of this interaction in its anorectic activity was studied in rats. At doses ranging from 2.5 to 10 mg/kg quipazine markedly reduced brain 5-hydroxyindolacetic acid concentrations without significant effects on steady-state levels of serotonin, noradrenaline and dopamine. Striatal levels of homovanillic acid were significantly reduced by 10 mg/kg of quipazine but not modified by a dose of 5 mg/kg. Quipazine counteracted the decrease of brain serotonin induced by fenfluramine but did not significantly modify the effect of 6-hydroxydopamine on brain nonadrenaline and dopamine. The decrease of food intake induced by 5 mg/kg of quipazine was completely prevented by pretreatment with methergoline but was not affected by an intraventricular injection of 6-hydroxydopamine or pretreatment with penfluridol, propranolol or phentolamine. The results indicate that at doses between 2.5 and 5 mg/kg quipazine specifically acts on brain serotonin and this interaction may be important for its anorectic activity.
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