Differential effects of cimetidine and ranitidine on imipramine demethylation and desmethylimipramine hydroxylation by human liver microsomes.

The effect of cimetidine and ranitidine on the demethylation of imipramine (IMI) and on the hydroxylation of desmethylimipramine (DMI) was studied in microsomes from four human livers. Cimetidine inhibited both demethylation of IMI and 2-hydroxylation of DMI, whilst the effect of ranitidine was not statistically significant. 2-hydroxylation of DMI is probably mediated by debrisoquine hydroxylase, a cytochrome P-450 isozyme that is monogenically controlled. The results suggest that cimetidine inhibits this enzyme.