The nature of microsomal monooxygenase inhibition by cimetidine

Abstract

A kinetic investigation of the inhibitory effect of cimetidine on the O-dealkylation of 7-ethoxyresorufin by rat liver microsomes has yielded linear Lineweaver-Burk plots which intersect in the second quadrant. Though technically compatible with non-competitive inhibition, the results are shown to be readily explained by the more realistic molecular concept of competitive inhibition by invoking the involvement of cytochrome P-450 isoenzymes with widely different KI values. Microsomal monooxygenase heterogeneity is also shown to provide a plausible explanation of other published results signifying the departure of chloramphenicol and phenacetin from the concept of competitive inhibition despite competition with substrate for the active-site haem group of cytochrome P-450.