Yamaguchi K, Suzuki K, Niho T, Shimora M, Ito C, Ohnishi H
Can J Physiol Pharmacol. 1983 Jun;61(6):619-25. doi: 10.1139/y83-095.
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.
研究了新型2,3-苯二氮䓬化合物托非索泮对以下方面的影响：正常大鼠水浸应激诱导的胃溃疡、嗅球切除（OB）大鼠固定应激诱导的胃溃疡；大鼠水浸应激引起的小肠推进以及家兔下丘脑电刺激引起的自主反应。在后者中，将结果与地西泮和γ-谷维素的结果进行了比较。托非索泮（30和100mg/kg，口服）以剂量依赖性方式显著抑制正常大鼠水浸应激诱导的胃溃疡。与未应激大鼠相比，固定应激负荷增加了OB大鼠胃溃疡的发生率和平均指数。托非索泮（100mg/kg，口服）显著抑制OB大鼠应激负荷诱导的胃溃疡。水浸应激负荷导致大鼠小肠推进显著增加。托非索泮（100mg/kg，口服）使这种增加恢复到对照水平。托非索泮（1.0mg/kg，静脉注射，或0.1mg/kg脑室内注射）抑制家兔下丘脑内侧区域电刺激诱导的耳微血管收缩、耳垂温度降低和瞳孔散大。然而，地西泮和γ-谷维素未能抑制对下丘脑内侧刺激的自主反应。从这些结果可以得出结论，托非索泮可能通过干预中枢自主区域，即下丘脑，以不同于地西泮的作用方式恢复应激负荷诱导的自主异常。
