The inhibition of c-AMP-phosphodiesterase by phenobarbitone.

The early effects of phenobarbitone, theophylline, thyroxine and of combinations of these drugs, on rat liver microsomal aniline hydroxylase activity, were studied, and the results were compared with the effect of phenobarbitone on purified c-AMP-phosphodiesterase in vitro. The stimulatory effect of phenobarbitone on hepatic microsomal aniline hydroxylase activity was found to be simulated by theophylline, and also by thyroxine. When phenobarbitone and thyroxine were used, the effect was approximately equal to the sum of the individual effects, but no summation was seen when phenobarbitone and theophylline were used. Phenobarbitone caused an inhibition of c-AMP-phosphodiesterase activity in vitro. The magnitude of this inhibitory effect was found to be dependent on the dose of phenobarbitone. The significance of c-AMP-phosphodiesterase inhibition by phenobarbitone is discussed.