INHIBITION OF RIBOFLAVIN METABOLISM IN RAT-TISSUES BY CHLORPROMAZINE, IMIPRAMINE, AND AMITRIPTYLINE

Riboflavine (vitamin B2), phenothiazine drugs, and tricyclic antidepressants have similar structures. Whether the 2 types of drugs affect the conversion of riboflavine into its active coenzyme derivative, FAD, in rat tissues, was studied. Chlorpromazine, a phenothiazine derivative, and imipramine and amitriptyline, both tricyclic antidepressants, each inhibited the incorporation of [14C]riboflavine into [14C]FAD in liver, cerebrum, cerebellum and heart. A variety of psychoactive drugs structurally unrelated to riboflavine were ineffective. Chlorpromazine, imipramine and amitriptyline in vitro inhibited hepatic flavokinase, the first of 2 enzymes in the conversion of riboflavine to FAD. Evidence was obtained that chlorpromazine administration for 3 or 7 wk at doses comparable on a weight basis to those used clinically has significant effects upon riboflavine metabolism in the animal as a whole; the activity coefficient of erythrocyte glutathione reductase, an FAD-containing enzyme used as an index of riboflavine status physiologically, was elevated, a finding compatible with a deficiency state. The urinary excretion of riboflavine was more than twice that of age- and sex-matched pair-fed control rats and after administration of chloropromazine for 7 wk, tissue levels of flavine mononucleotide and FAD were significantly lower than those of pair-fed littermates, despite consumption of a diet estimated to contain 30 times the recommended dietary allowance. Certain psychotropic drugs interfere with riboflavine metabolism at least in part by inhibiting the conversion of riboflavine to its coenzyme derivatives, and as a consequence of such inhibition, the overall utilization of the vitamin is impaired.