Effect of a combination of ecabet sodium and cimetidine on experimentally induced gastric lesions and gastric mucosal resistance to ulcerogenic agents in rats.
We studied the effect of single oral administration of ecabet sodium (ecabet), a gastroprotective agent, in combination with the histamine H2-receptor antagonist cimetidine on gastric acid secretion, mucosal prostaglandin E2 (PGE2) production and experimentally induced acute hemorrhagic gastric lesions in rats. The effect repeated administration of ecabet in combination with cimetidine on the vulnerability of gastric mucosa to the ulcerogenic agents 0.6N HCl and aspirin was also studied. In pylorus-ligated rats, oral administration of cimetidine reduced gastric acid secretion, whereas ecabet did not affect the cimetidine-induced reduction in acid secretion. On the other hand, ecabet increased the capacity of gastric mucosa to synthesize PGE2, while cimetidine showed no effect on this parameter either in the presence of absence of ecabet. Both ecabet and cimetidine inhibited the formation of aspirin-induced gastric mucosal lesions, and the combination of ecabet and cimetidine showed a more potent inhibition than either drug alone. After cessation of repeated administration of cimetidine, but not ecabet, the 0.6N HCl- and aspirin-induced gastric lesions were significantly aggravated. The co-administration of ecabet improved the cimetidine-induced aggravation of these gastric lesions. These results suggest that ecabet in combination with cimetidine augments the antiulcer effect of cimetidine and improves the cimetidine-induced increase in gastric mucosal vulnerability to the ulcerogenic agents.
Kinoshita
M
M
Pharmacological Research Laboratory, Tanabe Seiyaku Co., Ltd., Saitama, Japan.
Noto
T
T
Tamaki
H
H
D045784:Abietanes; D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001241:Aspirin / Q000494:pharmacology; D002927:Cimetidine / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D015232:Dinoprostone / Q000096:biosynthesis; D004224:Diterpenes / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005753:Gastric Mucosa / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D006851:Hydrochloric Acid / Q000494:pharmacology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D013276:Stomach Ulcer / Q000188:drug therapy*
D045784:Abietanes; D000897:Anti-Ulcer Agents; D004224:Diterpenes; C061681:ecabet; D002927:Cimetidine; D015232:Dinoprostone; D006851:Hydrochloric Acid; D001241:Aspirin