title: Pharmacological profiles of a new antiulcer agent, SWR-215.
abstract: We investigated the effects of a new antiulcer agent, SWR-215 ([[(1,2-dihydro-2-oxo-4-quinolinyl)methyl]thio]-N-[[[4-(1-piperidinyl methyl)-2-pyridinyl]oxy]-Z-2-butenyl]acetamide), on histamine H2-receptors, gastric acid secretion and various acute experimental gastric lesions. SWR-215 showed unsurmountable histamine H2-antagonism on isolated guinea-pig atrium. In gastric secretion studies, SWR-215 exhibited potent and durable inhibitory effects, and the antisecretory activities were much stronger than that of roxatidine acetate hydrochloride (roxatidine): 5 times stronger on basal acid secretion in pylorus ligated rats, 11 times stronger on histamine-stimulated acid secretion in acute fistula rats, and 2 times stronger on histamine stimulated acid secretion in Heidenhain-pouch dogs, respectively. In various experimental acute gastric lesion studies, SWR-215 potentially inhibited almost all acute gastric and duodenal lesions compared with roxatidine, especially indomethacin-induced and HCl-ethanol-induced gastric lesions, and the inhibitory effects were exhibited at the same or lower doses than those which caused the antisecretory effect. Furthermore, it was considered that the mucosal protective effect of SWR-215 was probably unrelated to the endogenous prostaglandin system in gastric mucosa. These results suggest that SWR-215 possesses both durable antisecretory and mucosal protective effects, and is expected to be a useful drug for the treatment of patients with peptic ulcers.
authors.affiliation: Research Department, Sawai Pharmaceutical Co., Ltd., Asahi-ku, Osaka, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Kataoka
authors.forename: T
authors.initials: T
authors.lastname: Isoi
authors.forename: T
authors.initials: T
authors.lastname: Kiso
authors.forename: C
authors.initials: C
authors.lastname: Tanaka
authors.forename: R
authors.initials: R
authors.lastname: Shinkawa
authors.forename: T
authors.initials: T
authors.lastname: Kakita
authors.forename: T
authors.initials: T
authors.lastname: Shogaki
authors.forename: M
authors.initials: M
authors.lastname: Furukawa
authors.forename: Y
authors.initials: Y
authors.lastname: Ohtsubo
mesh_terms: D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology*; D004285:Dogs; D005260:Female; D005744:Gastric Acid / Q000378:metabolism; D005753:Gastric Mucosa / Q000187:drug effects; D006168:Guinea Pigs; D006635:Histamine H2 Antagonists / Q000494:pharmacology*; D008297:Male; D010880:Piperidines / Q000494:pharmacology*; D011804:Quinolines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011970:Receptors, Histamine H2 / Q000187:drug effects
chemical_list: D000897:Anti-Ulcer Agents; D006635:Histamine H2 Antagonists; D010880:Piperidines; D011804:Quinolines; D011970:Receptors, Histamine H2; C106052:SWR 215