Effects of the new H2-receptor antagonist 3-amino-4-[4- [4- (1-piperidinomethyl)-2-pyridyloxy]-cis-2-butenylamino]-3-cyclobutene-1, 2- dione hydrochloride on gastric acid secretion and ulceration.
The effect of 3-amino-4-[4-[4-(1-piperidinomethyl)-2-pyridyloxy]-cis- 2-butenylamino]-3-cyclobutene-1,2-dione hydrochloride (IT-066), a new H2-receptor antagonist, on gastric acid secretion and on various experimental ulcers was investigated. IT-066 showed very potent and long lasting antisecretory action in pylorus ligated rats. The inhibitory potency of IT-066 given subcutaneously for gastric acid secretion was 1285 and 44 times higher than for cimetidine and famotidine, respectively. The duration of the inhibitory action of IT-066 was significantly longer than that of famotidine and cimetidine. In pylorus ligated rats, IT-066 showed almost 20 times higher potency than omeprazole with intraduodenal administration, and almost the same duration of action as omeprazole with one tenth the dose in oral administration. IT-066 showed a powerful protective effect on various experimental ulcer models. The potency of IT-066 administered subcutaneously was significantly higher compared with that of cimetidine, famotidine and omeprazole. IT-066 given orally also showed a more powerful antiulcer effect than cimetidine and omeprazole, and was comparable with that of famotidine in restraint and water immersion stress and cold-stress plus indometacin induced ulcer models in rats. These results suggest that IT-066 has powerful and long lasting antisecretory and antiulcer effects and is a useful antisecretory drug for treatment of peptic ulcer diseases.
Muramatsu
M
M
Department of Pharmacology, Research Center, Taisho Pharmaceutical Co., Ltd., Saitama, Japan.
Isobe
Y
Y
Arai
I
I
Hirose-Kijima
H
H
Usuki-Ito
C
C
Nagai
H
H
Aihara
H
H
Otomo
S
S
D000818:Animals; D000897:Anti-Ulcer Agents; D003080:Cold Temperature; D003543:Cysteamine; D004381:Duodenal Ulcer / Q000139:chemically induced / Q000209:etiology / Q000517:prevention & control; D005744:Gastric Acid / Q000378:metabolism*; D006632:Histamine; D006635:Histamine H2 Antagonists / Q000494:pharmacology*; D007213:Indomethacin; D008297:Male; D009853:Omeprazole / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology*; D011708:Pylorus / Q000502:physiology; D011725:Pyridines / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013276:Stomach Ulcer / Q000139:chemically induced / Q000209:etiology / Q000517:prevention & control; D013312:Stress, Physiological / Q000150:complications
D000897:Anti-Ulcer Agents; D006635:Histamine H2 Antagonists; D010880:Piperidines; D011725:Pyridines; C063924:IT 066; D003543:Cysteamine; D006632:Histamine; D009853:Omeprazole; D007213:Indomethacin