GUANETHIDINE AND RELATED AGENTS. II. METABOLISM BY HEPATIC MICROSOMES AND ITS INHIBITION BY DRUGS

The metabolism of guanethidine, debrisoquin and guanoxan by an oxygen-and reduced nicotinamide adenine dinucleotide phosphaterequiring enzyme system in hepatic microsomes of the rat is inhibited by desipramine. The metabolism of these compounds also is inhibited by other tricyclic antidepressants, phenothiazines and amines such as metaraminol. The low dose of desipramine required for inhibition in the rat in vivo suggests the possibility of a similar inhibition of the metabolism of drugs by desiprainine in man.