Hepatic aminopyrine N-demethylase system: effect of cyanide on microsomal N-demethylase activity

Cyanide, an inhibitor of many hemoproteins, was shown to affect a number of microsomal drug-metabolizing activities catalyzed by cytochrome P-450. The N-demethylation reaction of aminopyrine was inhibited noncompetitively by this inhibitor in microsomal preparations from rats. The binding reaction of aminopyrine with microsomal cytochrome P-450 was also modified by cyanide, and an abnormal aminopyrine-induced difference spectrum of microsomes by cyanide, and an abnormal aminopyrine-induced difference spectrum of microsomes appeared when cyanide was added to the reaction mixture. Partial dissociation of cytochrome P-450. Cyanide complex by aminopyrine was observed by spectrophotometrical and epr spectroscopic methods. These results suggest that aminopyrine and cyanide reciprocally affect binding with cytochrome P-450 and modification by cyanide of aminopyrine binding reaction with the hemoprotein produces an inhibition of N-demethylase activity.