Reactions of sulfenic acid with 2-mercaptoethanol: a mechanism for the inhibition of gastric (H+-K+)-adenosine triphosphate by omeprazole.

The reactions of omeprazole, a potent proton pump inhibitor (PPI) were investigated in the presence of 2-mercapotoethanol. Reactions were monitored in solutions buffered to pH values ranging 2.0-8.0 using differential pulse polarography (DPP) at the static mercury drop electrode (SMDE). The fast, sensitive and selective electrochemical technique facilitated successive recordings of voltammograms (peak current (nA) vs. peak potential (volts vs. Ag/AgCl)) for all analytes in situe, including the 2-mercaptoethanol. In acidic solutions and in the presence of 2-mercaptoethanol, omeprazole undergoes degradation into three compounds, the first is a cyclic sulfenamide (D+), previously believed to be the active inhibitor of the H+, K+-ATPase, the second is the omeprazole dimer, and the third is the disulfide believed to be the product of reaction between 2-mercaptoethanol and D+. The cyclic sulfenamide (D+) solution was found to be stable in solutions containing 2-mercaptoethanol having pH values: 2.0, 4.0, and 6.0. This finding proved conclusively that the cyclic sulfenamide is not reactive toward the 2-mercaptoethanol. In contrast to previous reports, the conversion of the sulfenic acid intermediate into D+ was found to be irreversible. Due to this irreversibility, D+ and sulfenic acid were not rapidly interconvertable. The present work suggests that the active inhibitor is the sulfenic acid. (c) 2006 Wiley-Liss, Inc. and the American Pharmacists Association.