Inhibition of Riboflavin Metabolism in Cardiac and Skeletal Muscles of Rats by Quinacrine and Tetracycline

The acridine derivative quinacrine, the broad spectrum antibiotic tetracycline, and the 4-aminoquinoline compound chloroquine, all have antimalarial properties. Based on our recent proposal that the antimalarial effects of certain drugs may be related to their inhibition of riboflavin metabolism, the present study was conducted to determine whether these drugs will act as riboflavin antagonists. Adult Holtzman rats were injected intraperitoneally with either tetracycline, quinacrine, or chloroquine for three days at a dose of 20mg/kg body weight. Agematched, pair-fed control rats received an equivalent volume of normal saline. One hour prior to sacrifice, all rats received a single subcutaneous injection of [14C]riboflavin (25μCi/kg body weight). After decapitation, heart and skeletal muscle surrounding the femur were excised, and aliquots were analyzed for [14C]flavin adenine dinucleotide (FAD) formation. Compared with results in controls, rats treated with either tetracycline or quinacrine exhibited diminished formation of [14C]FAD in heart and in skeletal muscle. By contrast, chloroquine had no significant inhibitory effect upon [14C]FAD formation in either heart or skeletal muscle. These data provide evidence that tetracycline and quinacrine, agents with recognized antimalarial properties, each diminish FAD biosynthesis in heart and in skeletal muscle. By contrast, chloroquine has no effect upon FAD biosynthesis. This study provides evidence supporting a possible link between decreased formation of FAD and the action of certain tricyclic and tetracyclic drugs effective against malaria.