Kazushige Sakai, Michitaka Akima and Iwao Katsuyama (#)
Central Research Laboratories, Chugai Pharmaceutical Co., Ltd., 3-41-8
Takada, Toshima-ku, Tokyo 171-8545, Japan
(#) Present address: Biochemical and Pharmacological Laboratories Inc.,
Tondabayashi, Osaka 584-0023, Japan
Abstract: The anti-ulcer effects of nicorandil [N-(2-hydroxyethyl)nicotinamide
nitrate ester] were examined on water-immersion plus restraint stress-induced
and aspirin-induced gastric ulcers in rats, compared with those of cimetidine.
Nicorandil (3 and 10 mg/kg) given orally to rats dose-dependently inhibited
the development of acid-related damage (water-immersion- and aspirin-induced
gastric lesions) in the models. Cimetidine (50 mg/kg, p.o.) also had anti-ulcer
effects in the same models. However, in the presence of glibenclamide (20
mg/kg, i.v.), an antagonist of KATP channels, nicorandil did
not inhibit the formation of gastric lesions. Nicorandil (10 mg/kg) given
intraduodenally (i.d.), like cimetidine (50 mg/kg), significantly reduced
the volume of the gastric content, total acidity and total acid output in
the pylorus ligation model. Glibenclamide reversed the changes caused by
i.d. nicorandil. I.v. infusion of nicorandil (20 microg/kg per min) significantly
increased gastric mucosal blood flow, without affecting blood pressure and
heart rate, but the increase in the blood flow was not observed after i.v.
treatment with glibenclamide (20 mg/kg). These results indicate that nicorandil
administered orally to rats produces the anti-ulcer effect by reducing the
aggressive factors and by enhancing the defensive process in the mucosa
through its KATP-channel-opening property.
Keywords: Nicorandil, Anti-ulcer effect, Gastric acid secretion, Gastric
mucosal blood flow, Opening of KATP channels