Effects of a New Histamine H2-Receptor Antagonist, Z-300, on Gastric Secretion and Gastro-Duodenal Lesions in Rats: Comparison with Roxatidine

• Published in: Japanese journal of pharmacology 1992-07, Vol.59 (3), p.275-289
• Main Authors: Okabe, Susumu, Takagi, Keiko, Igata, Hideki, Kato, Shinichi, Shimosako, Kenichi, Yamaji, Yoshiaki, Seiki, Masao
• Format: Article
• Language: English
• Subjects: Acetamides - administration & dosage; Acetamides - pharmacology; Administration, Oral; Animals; Biological and medical sciences; Digestive system; Dogs; Duodenum - drug effects; Duodenum - pathology; Female; Gastric Acid - metabolism; Gastric Mucosa - metabolism; Gastric secretion; Gastro-duodenal lesions; Histamine H2 Antagonists - pharmacology; Histamine H2-receptor antagonist; Male; Medical sciences; Peptic Ulcer - pathology; Pharmacology. Drug treatments; Piperidines - administration & dosage; Piperidines - pharmacology; Rats; Rats, Inbred Strains; Stomach - drug effects; Stomach - pathology; Stomach Ulcer - pathology; Ulcer healing; Z-300
• ISSN: 0021-5198; 1347-3506
• DOI: 10.1016/S0021-5198(19)37624-3

We examined the effects of a new compound, N-[3-[3-(piperidinomethyl)phenoxy]-propyl]-2-(2-hydroxyethyl-1-thio)acetamido-2-(4-hydroxy benzoyl)benzoate (Z-300), on the histamine H2-receptor, gastric secretion in rats and dogs, and acute gastro-duodenal lesions or chronic gastric ulcers in rats. Roxatidine acetate hydrochloride (roxatidine), a known histamine H2-receptor antagonist, was used as a reference compound. The pA2 values for Z-300 and roxatidine for the isolated guinea pig atrium were 6.8 and 7.0, respectively. These agents at 7 hr in the case of histamine-stimulation. Oral Z-300 significantly protected the gastric mucosa from water-immersion stress-, indomethacin-, aspirin- and HCl* ethanol-induced lesions and protected the duodenal mucosa against mepirizole- and cysteamine-induced ulcers. These effects on gastric secretion and lesion formation were, as a whole, stronger than those observed with roxatidine. Z-300, but not roxatidine, significantly accelerated the spontaneous healing of acetic acid ulcers induced in rats and prevented the delay in ulcer healing caused by indomethacin. The mechanism of action of Z-300 on acute lesions and chronic ulcers appears to be mostly related to its potent antisecretory and mucosal-protective activities.