[Effects of IT-066, a new histamine H2-receptor antagonist, on gastric acid secretion and experimental gastric ulcers in rats and dogs].
We examined the effects of a new histamine H2-receptor antagonist, 3-amino-4-(4-[4-(1-piperidinomethyl)-2-pyridyloxy]-cis-2- butenylamino)-3- cyclobutene-1,2-dione hydrochloride (IT-066), on gastric acid secretion and the healing process of experimental ulcers in rats and dogs. Famotidine, a well-established H2-receptor antagonist, was used as the reference drug. Male Donryu rats (240-260 g) and Beagle dogs of both sexes (8-10 kg), having Heidenhain pouches, were used. IT-066 dose-dependently inhibited the basal gastric acid secretion of rats, and this inhibition significantly persisted for 12 hr. In addition, the agent significantly inhibited histamine-stimulated acid secretion in both normal rats and rats with acetic acid ulcers. IT-066, given p.o. twice daily for 2 and 3 weeks after ulceration, significantly accelerated both spontaneous and delayed healing (with indomethacin) of acetic acid-induced gastric ulcers in rats. The effects of IT-066 on acid secretion and ulcer healing were almost the same or slightly more potent than those observed with famotidine. IT-066, when given i.v. or p.o., dose-dependently inhibited the gastric acid secretion stimulated by histamine, pentagastrin, or carbachol in dogs. The antisecretory effects of the agent on histamine-stimulated acid secretion significantly persisted for more than 6 hr. These results indicate that IT-066 appears to be a promising antisecretory and anti-ulcer agent.
Okabe
S
S
Department of Applied Pharmacology, Kyoto Pharmaceutical University, Japan.
Nishida
T
T
Igata
H
H
Takagi
K
K
D000085:Acetates; D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002217:Carbachol / Q000037:antagonists & inhibitors; D003864:Depression, Chemical; D004285:Dogs; D015738:Famotidine / Q000494:pharmacology / Q000627:therapeutic use; D005260:Female; D005744:Gastric Acid / Q000378:metabolism*; D006633:Histamine Antagonists; D006635:Histamine H2 Antagonists / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D010418:Pentagastrin / Q000037:antagonists & inhibitors; D010880:Piperidines / Q000494:pharmacology* / Q000627:therapeutic use; D011725:Pyridines / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D011919:Rats, Inbred Strains; D013276:Stomach Ulcer / Q000139:chemically induced / Q000188:drug therapy*
D000085:Acetates; D000897:Anti-Ulcer Agents; D006633:Histamine Antagonists; D006635:Histamine H2 Antagonists; D010880:Piperidines; D011725:Pyridines; C063924:IT 066; D015738:Famotidine; D002217:Carbachol; D010418:Pentagastrin