Role of brain monoamines in the anorectic activity of mazindol and d-amphetamine in the rat

The interaction of mazindol and d-amphetamine with brain monoamines was studied in rats. At each dose used, both compounds markedly counteracted the decrease of brain noradrenaline induced by 6-hydroxydopamine while only at high doses they did significantly reduce the effect of 6-hydroxydopamine on brain dopamine. Unlike d-amphetamine, mazindol significantly counteracted the decrease of brain serotonin induced by fenfluramine. The anorectic effect of mazindol and of d-amphetamine was markedly reduced by an electrolytic lesion at the level of the ventral noradrenergic bundle but not by an electrolytic lesion of the nucleus raphe medianus. An intrastriatal injection of 6-hydroxydopamine significantly reduced the effect of mazindol but not that of d-amphetamine. The results indicate that both compounds may block noradrenaline uptake in the brain while their effect on dopamine uptake is less evident. Ulike d-amphetamine, mazindol appears to inhibit serotonin uptake also. In addition, the integrity of the noradrenergic neurons in the brain appears to be an important condition for these drugs to exert their anorectic effect.