Jpn. J. Pharmacol. 72 (2), 183-190 (1996)

Differential Effect of Benexate Hydrochloride Betadex on Prostaglandin Levels in Stomach and Inflammatory Site in Rats

Yozo Hori, Kunihiro Odaguchi, Hirokuni Jyoyama, Kiyoshi Yasui and Takuji Mizui

Division of Pharmacology, Discovery Research Laboratories II, Shionogi & Co., Ltd., 3-1-1 Futaba-cho, Toyonaka, Osaka 561, Japan

Abstract: We compared the effects of an anti-ulcer agent, benexate hydrochloride betadex (BHB), on prostaglandin (PG) levels in gastric tissue and inflammatory exudate in untreated and indomethacin-treated rats. BHB (100, 300 and 1000 mg/kg, p.o.) showed dose-dependent inhibition of gastric mucosal lesions induced by indomethacin (30 mg/kg, p.o.). Sustained decrease of PGs (PGE2 and 6-keto-PGF1alpha) in the gastric wall was observed from 0.5 to 6 hr after indomethacin treatment. BHB (300 and 1000 mg/kg) dose-dependently led to recovery of the indomethacin-induced decrease of gastric PGs at 1 and 6 hr after dosing. It did not antagonize the indomethacin-induced decrease of PG levels in the pleural exudate of carrageenin pleurisy nor did it affect the anti-inflammatory effects of indomethacin. BHB (100 to 1000 mg/kg) alone increased gastric PGE2 by 61% to 113%, while it decreased PGE2 levels in the pleural exudate by 9% to 71% at 6 hr after dosing. These results suggest that sustained increase of gastric PGE2 by BHB could be responsible for protection against indomethacin-induced gastric mucosal lesions and that BHB is a suitable anti-ulcer agent for NSAlDs without compromising their anti-inflammatory effects.

Keywords: Benexate hydrochloride betadex, Gastric mucosa, Indomethacin, Prostaglandin, Pleurisy

Copyright© The Japanese Pharmacological Society 1996

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