Effect on gastric mucus of the proton pump inhibitor leminoprazole and its cytoprotective action against ethanol-induced gastric injury in rats.

The effect of leminoprazole ((+-)-2-[[2-(isobutyl-methylamino)benzyl]sulfinyl]-1H-benzimidazol e, NC-1300-O-3, CAS 104340-86-5), a new compound being developed as an inhibitor of the gastric mucosal proton pump (H+,K(+)-ATPase), on gastric mucus secretion was studied by a biochemical method measuring the gastric mucin content in rats. Oral administration of leminoprazole (30 mg/kg) strongly inhibited the hemorrhagic lesions induced by 60% ethanol containing 0.15 mol/l HCl (acid-ethanol) administered 1 h later. Leminoprazole significantly inhibited the acid-ethanol-induced reduction of the mucin content in the surface mucosa including the mucus gel layer, but no significant effect could be obtained on the reduction of mucin present in the deep layer of the corpus and antral mucosa. Leminoprazole given to rats not treated with acid ethanol accelerated the secretion of deep mucosal mucus and increased significantly the content of soluble mucus which was recovered from the gastric luminal contents to about 200% of control, but failed to produce any significant change in the mucus content present in the surface mucosal and the mucus gel layers. The effect of leminoprazole on gastric mucus secretion might contribute to healing the peptic ulcer diseases and may be involved in the cytoprotective mechanism of this drug.