Abstract
The effects of tofisopam on gastric functions were examined in rats. Intracerebroventricular (i.c.v.) injection of tofisopam (50 or 100 μg) increased both basal gastric acid output and mucosal blood flow (MBF) in rats anesthetized with urethane, while intravenous injection of tofisopam (10 mg/kg) did not change the basal gastric acid output. Ten μg of tofisopam, i.c.v., a dose which did not show any effect on the basal gastric acid output, significantly inhibited the decrease in gastric acid output induced by noradrenaline (5 μg, i.c.v.). Tofisopam (10 mg/kg, i.v. or 100 μg, i.c.v.) showed no effect on the increase in gastric acid output induced by electrical stimulation of the lateral hypothalamic area (LHA). These results, together with the previous findings, suggest that tofisopam (i.c.v.) acts on the nucleus dorsalis n. vagi and/or LHA and competes with noradrenaline. The gastric acid output was increased remarkably under water-immersion stress, and this increase lasted during the stress-loading, but the MBF did not show a corresponding increase. Pretreatment of rats with tofisopam (100 mg/kg, intraduodenal) significantly increased the MBF and inhibited the ulcer formation caused by the stress. From these results, tofisopam may restore the unbalance between sympathetic and parasympathetic nervous tones induced by stress-loading.
