Determination of Melting Point of Omeprazole and Other Sulfoxides by Instantaneous Method (CAT#: STEM-PPA-0120-YJL)

Introduction

The ultimate mediator of acid secretion is the Hþ/KþATPase (proton pump of the apical membrane of the parietal cell). This pump is unique to the parietal cells and a number of specific inhibitors of it have, therefore, been developed. The available compounds belong to the family of substituted benzimidazoles: omeprazole, lansoprazole, pantoprazole and rabeprazole. Esomeprazole is the more active S-enantiomer of omeprazole. These agents are especially useful in patients with hypergastrinemia and may be valuable in those patients whose peptic ulcer disease is not well controlled by H2-antagonists. These benzimidazoles are prodrugs. They become protonated in the secretory canaliculi. The protonated compounds rearrange to form a sulfenic acid and a sulfenamide. The onset of action for rabeprazole is particularly rapid because it is transformed into the active form already at pH 4.9 in the parietal cells. The sulfenamide interacts covalently with sulfhydryl groups at critical sites in the luminal domain of the membrane-spanning Hþ/Kþ-ATPase with subsequent formation of a disulfide bridge. Full inhibition occurs with two molecules of inhibitor bound per molecule of enzyme.