Yonago Acta medica 1993;36:35-46

Inhibitory Effect of Bifemelane on Stress-Induced Gastric Mucosal Lesions

Toshihiro Hamada, Yoshinori Kamisaki and Tadao Itoh

Department of Clinical Pharmacology, Faculty of Medicine, Tottori University, Yonago 683, Japan

The effects of bifemelane on stress-induced gastric mucosal lesions and gastric acid secretion were investigated in rats. A water-immersion restraint stress produced gastric lesions associated with a decrease in brain noradrenaline content and an increase in plasma catecholamine (noradrenaline, adrenaline) and corticosterone levels. Bifemelane inhibited gastric lesions (ulcer index) in a dose-dependent manner, as well as diazepam. A stress-induced decrease in brain noradrenaline content was counteracted by either bifemelane or diazepam. Although diazepam attenuated both the plasma catecholamine and corticosterone levels, bifemelane induced even further increases in these levels. In pyrolus-ligated rats, both basal (unstimulated) and pentagastrin- or histamine-stimulated acid secretion was reduced by bifemelane in a dose-dependent manner. However, in vagotomized rats, bifemelane did not inhibit acid secretion. On the other hand, diazepam induced a decrease in acid secretion in both normal and vagotomized rats. Carbachol-stimulated acid secretion in vagotomized rats was not altered by bifemelane. These results suggest that bifemelane may play an anti-ulcerogenic role in decreasing gastric acid secretion through both the hypothalamo-vagal and sympathetic pathways.

Key words: bifemelane; diazepam; gastric acid secretion; stress ulcer; vagotomy

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