Inhibitory effect of histamine H3-receptor antagonist cimetidine against copper(II)/ascorbate-mediated protein damage.

Abstract

The inhibition of ascorbate-mediated protein damage by the histamine H2-receptor antagonist, cimetidine, was chemically studied. In the presence of copper(II) ion, ascorbate gave rise to oxidative modification of both a protein and a histidine derivative under simulated physiological conditions (pH 7.2, 37°C), whereas the reactions were entirely inhibited by the addition of cimetidine. The inhibition of protein damage resulted in almost total disappearance of cimetidine within 24 hr and the appearance of two major products, a species (2) assigned as the 2-imidazolone derivative of cimetidine and cimetidine sulfoxide (3). The mechanism for the protective effect of cimetidine against copper(II)/ascorbatemediated protein damage is discussed.