The present study was undertaken to determine whether treatment with
chlorpromazine accelerates the depletion of tissue stores of
flavin adenine dinucleotide during dietary
riboflavin deficiency. These investigations derived their impetus from earlier findings that low doses of
chlorpromazine in rats fed abundant
riboflavin increase urinary
riboflavin excretion and reduce hepatic
flavin stores. From 6 to 10 days after beginning to feed on a
riboflavin-deficient diet, rats treated with
chlorpromazine, 2 mg/kg
body weight twice daily, had approximately twice the urinary
riboflavin excretion of that of pair-fed saline-treated controls. When the
riboflavin-deficient diets and
chlorpromazine treatments were extended for 3 weeks and the animals killed,
FAD levels in liver, kidney, and heart were markedly lower in
drug-treated than in saline-treated animals. When studies were extended for 7 weeks, tissue
FAD levels in saline-treated animals declined further and were equal to those of
chlorpromazine-treated rats after only 3 weeks of dietary deficiency. Thus,
chlorpromazine treatment accelerated urinary
riboflavin loss and accelerated tissue depletion of
FAD levels during dietary
riboflavin deficiency. Brain levels of
FAD by contrast were relatively resistant to both dietary
riboflavin withdrawal and treatment with
chlorpromazine. Subsequent studies showed that urinary
riboflavin excretion began to increase within 6 hr of treatment with
chlorpromazine. It is concluded that significant
riboflavin depletion occurs following treatment with low doses of
chlorpromazine, both in animals fed a normal diet and in animals fed a
riboflavin-deficient diet, particularly during the early stages of deficiency.