Action of Some Centrally Active Drugs and Heavy Metals on In Vitro Oxidation of Dopamine by Rat Brain Tissue

Abstract

The effect of chlorpromazine, amitryptyline, amphetamine, diphenhydramine, and iproniazid on the in vitro oxidation of dopamine to melanin by rat brain mitochondrial preparation was investigated. Chlorpromazine and amitryptyline very markedly inhibited the oxidation (ED50 60 and 180 μM, respectively) while iproniazid was ineffective. Other drugs were moderately active. The reaction was enzyme catalyzed and could not be ascribed to the anionic component. Chronic administration of chlorpromazine and amitryptyline (19 and 9.5 mg/kg, i.p.) produced a biphasic response characterized by stimulation of melanogenesis during the first 2–3 weeks followed by inhibition. On the other hand, physostigmine and choline markedly stimulated the oxidation process. The chronic ingestion of heavy metals; mercury, lead, and cadmium, up to toxic levels had no effect on the in vitro oxidation of dopamine.