Effect of roseoflavin on microsomal drug-metabolizing enzyme system

The Bs vitamin antagonist 7-methyl-8dimethylamino-IOD-ribityl-isoalloxazine, roseoflavin (ROF) product of Streptomyces strain no. 768, discovered [ 1,2] has been shown to be a substrate of flavokinase (EC 2.7.1.26). The false nucleotide formed might be built into the apo-old yellow enzyme and thereby inhibit the oxidation of NADH and NADPH [3]. ROF in vitro (< 50 @g/ml) has no effect on the NADPH cytochrome c reductase, anlline hy~oxy~~ and ~~opy~e ~-demethylase activity of isolated liver microsomes (data not shown). We have found that in rats kept on normal diet (BZ vitamin cont. 60 ppm), 4 mg/kg ROF (L&e 3 .OOO mg/kg in mice [I]) administered orally transiently prolongs the hexobarbital sleeping time (fig.1) showing that ROF’ in vivo is antagonist. The repeated administration of ROF in similar doses increases the hexobarbital sleeping time both in non-induced and phenobarbitalinduced animals. Now, we report the results of those experiments, where multiple doses of ROF were applied.