Effects of induction on the metabolism and cytochrome P-450 binding of harman and other β-carbolines

Abstract

1. The metabolism of harman by liver microsomes from non-induced, phenobarbitone (PB)-induced and 3-methylcholanthrene (MC)-induced mice was investigated. Initial reaction rates for harman disappearance were measured and showed a 4-fold induction by PB and a 10˙6-fold induction by MC.

2. The major metabolite formed with each microsomal preparation was identified as 6-hydroxyharman.

3. Microsomal cytochrome P-450 binding was measured for harman and other β-carbolines and both Type I and Type II binding spectra were observed, being dependent upon the mode of induction.