Direct effect of a nomifensine derivative on dopamine receptors

A study was made of the effects of nomifensine, 4'-hydroxynomifensine and 3',4'-dihydroxynomifensine on dopamine receptors in rat striatum and nucleus accumbens, using the dopamine-sensitive adenylate cyclase assay. Nomifensine and its 4'-hydroxy metabolite were both inactive as dopaminergic agonists. 3',4'-dihydroxynomifensine was, however, a potent agonist, being approximately 2 to 4 times less active than dopamine. The effects of dopamine and of 3',4'-dihydroxynomifensine were blocked by fluphenazine. It is concluded that the dopaminergic activity of 3',4'-dihydroxynomifensine is dependent upon the presence of the two hydroxyl groups.