title: Discovery of lansoprazole and its unique pharmacological properties independent from anti-secretory activity.
abstract: The proton pump inhibitors (PPIs) lansoprazole (LPZ) and omeprazole (OPZ) have been widely used for more than 20 years in the treatment of acid-related diseases such as gastro-duodenal ulcers and reflux esophagitis. Both LPZ and OPZ are derivatives of 2-[(2- pyridylmethyl)sulfinyl]-1H-benzimidazole, but LPZ has a trifluoroethoxy group in the molecule which seems to provide unique pharmacological properties in addition to its anti-secretory effect. For example, the anti-secretory effect of LPZ in rats was roughly 2 times greater than that of OPZ but the anti-ulcer effects were more than 10 times stronger than those of OPZ in rat models of reflux esophagitis, indomethacin-induced gastric antral ulcers and mepirizole-induced duodenal ulcers. It has also been reported that LPZ has acid-independent protective effects on the gastrointestinal mucosa, anti-inflammatory effects, and anti-bacterial effects on Helicobacter pylori. In contrast, recent advances in endoscopy have revealed that non-steroidal anti-inflammatory drugs (NSAIDs) often cause ulcers not only in the stomach and duodenum, but also in the small intestine in humans. Anti-secretory drugs such as PPIs and histamine H(2)-receptor antagonists (H(2)-RAs) are commonly used for the treatment of upper gastrointestinal mucosal lesions induced by NSAIDs. However, the effects of these drugs on NSAID-induced small intestinal lesions are still not fully understood. In this article, both a brief history of the discovery of LPZ and the unique pharmacological properties of LPZ independent from its anti-secretory action are reviewed, and the effects of PPIs and H(2)-RAs on NSAID-induced small intestinal lesions are discussed.
authors.affiliation: Department of Pharmacology & Experimental Therapeutics, Division of Pathological Sciences, Kyoto Pharmaceutical University, Misasagi, Yamashina, Kyoto 607-8414, Japan. h_satoh@mb.kyoto-phu.ac.jp
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Satoh
mesh_terms: D053799:2-Pyridinylmethylsulfinylbenzimidazoles / Q000494:pharmacology*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects; D004381:Duodenal Ulcer / Q000188:drug therapy / Q000473:pathology; D004942:Esophagitis, Peptic / Q000188:drug therapy / Q000473:pathology; D006635:Histamine H2 Antagonists / Q000494:pharmacology; D006801:Humans; D007421:Intestine, Small / Q000187:drug effects / Q000473:pathology; D064747:Lansoprazole; D009853:Omeprazole / Q000494:pharmacology*; D054328:Proton Pump Inhibitors / Q000494:pharmacology*; D051381:Rats; D013276:Stomach Ulcer / Q000188:drug therapy / Q000473:pathology
chemical_list: D053799:2-Pyridinylmethylsulfinylbenzimidazoles; D000894:Anti-Inflammatory Agents, Non-Steroidal; D006635:Histamine H2 Antagonists; D054328:Proton Pump Inhibitors; D064747:Lansoprazole; D009853:Omeprazole