MAZINDOL ANOREXIA IS MEDIATED BY ACTIVATION OF DOPAMINERGIC MECHANISMS

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Abstract
Anorexia in rats following injections of mazindol (0.1–8 mg/kg i.p.) could be antagonized by pretreatment with a dopamine receptor blocker (pimozide) but not by pretreatment with an α‐adrenoceptor blocker (phenoxybenzamine), a β‐adrenoceptor blocker ((‐)‐propranolol), or a 5‐hydroxytryptamine receptor blocker (methergoline). In rats with a unilateral lesion in the substantia nigra made by stereotaxic injection of 6‐hydroxydopamine, mazindol caused a dose‐dependent turning towards the lesioned side, indicating an indirect mechanism of action. This effect could be antagonized by pretreatment with a dopamine receptor blocker. In rats pretreated with reserpine and α‐methyl‐p‐tyrosine, mazindol did not have any motor stimulant action. In vitro studies with synaptosomes prepared from rat brain, indicated that mazindol blocks uptake and causes release of dopamine. It is concluded that the anorectic action of mazindol is mediated by a dopaminergic mechanism.