title: Tofisopam, a new 2,3-benzodiazepine. Inhibition of changes induced by stress loading and hypothalamic stimulation.
abstract: Effects of tofisopam, a new 2,3-benzodiazepine compound, were investigated on the following: gastric ulceration, induced by water-immersion stress in normal rats and by immobilization stress in olfactory-bulbectomized (OB) rats; and propulsion of the small intestine caused by water-immersion stress in rats and autonomic responses to electrical stimulation of the hypothalamus in rabbits. In the latter, the results were compared with those of diazepam and gamma-oryzanol. Tofisopam (30 and 100 mg/kg, po) significantly inhibited the gastric ulceration induced by water-immersion stress in normal rats in a dose-dependent manner. Immobilization-stress loading increased the incidence and average index of gastric ulceration in OB rats, compared with nonstressed rats. Tofisopam (100 mg/kg, po) significantly inhibited the gastric ulceration induced by stress loading in OB rats. Water-immersion stress loading induced a significant increase in intestinal propulsion in rats. This increase was reversed to control levels by tofisopam (100 mg/kg, po). Tofisopam (1.0 mg/kg, iv, or 0.1 mg/kg by intracerebrospinal injection) inhibited the constriction of ear microvessels, the decrease in earlobe temperature, and mydriasis induced by electrical stimulation of the medial hypothalamic area in rabbits. However, diazepam and gamma-oryzanol failed to inhibit the autonomic responses to medial hypothalamic stimulation. From these results, it can be concluded that tofisopam restores the autonomic abnormality induced by stress loading possibly via intervention in the central autonomic area, i.e., the hypothalamus, by an action different from that of diazepam.
mesh_terms: D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology*; D001569:Benzodiazepines / Q000494:pharmacology*; D004558:Electric Stimulation; D007031:Hypothalamus / Q000502:physiology*; D007421:Intestine, Small / Q000502:physiology; D008297:Male; D009830:Olfactory Bulb / Q000601:surgery; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains; D013276:Stomach Ulcer / Q000188:drug therapy* / Q000209:etiology; D013312:Stress, Physiological / Q000150:complications*
chemical_list: D014151:Anti-Anxiety Agents; D001569:Benzodiazepines; C012582:tofisopam