Ohnishi H, Ito C, Suzuki K, Niho T, Shimora M, Yamaguchi K
Nihon Yakurigaku Zasshi. 1981 Sep;78(3):139-44.
Effects of tofisopam on the gastric ulceration induced by immobilization stress in olfactory-bulbectomized rats, propulsion of the small intestine caused by water immersion-stress in rats and autonomic responses to electrical stimulation of the hypothalamus in rabbits were investigated. Immobilization stress loading of 16.5 hours each for 10 days caused the augmentation of incidence and average index of gastric ulceration in olfactory-bulbectomized rats, compared with non-treated rats. Tofisopam 100 mg/kg, p.o. significantly inhibited the gastric ulceration in olfactory-bulbectomized rats. Water immersion-stress loading for 2 hours caused a significant increase in propulsion of the small intestine in rats. This increase was reversed to control levels after the oral administration of tofisopam in a dose of 100 mg/kg. Tofisopam at dose of 1 mg/kg i.v. inhibited the contraction of ear microvessels, the decrease in earlobe temperature and the mydriasis induced by electrical stimulation of the medial hypothalamic area in rabbits, Moreover, these inhibitions were also shown by the intra-cerebrospinal injection of tofisopam at a dose of 0.1 mg/kg. From these results, it is concluded that tofisopam could restore the autonomic abnormality induced by stress-loading and exerts such effects by acting on the hypothalamus, an area of the brain, which regulates autonomic nervous functions.
研究了托非索泮对嗅球切除大鼠因制动应激诱导的胃溃疡、对大鼠水浸应激引起的小肠推进以及对家兔下丘脑电刺激的自主神经反应的影响。与未处理的大鼠相比，对嗅球切除大鼠连续10天每天进行16.5小时的制动应激加载，导致胃溃疡的发生率和平均指数增加。口服100mg/kg托非索泮可显著抑制嗅球切除大鼠的胃溃疡。2小时的水浸应激加载导致大鼠小肠推进显著增加。口服100mg/kg托非索泮后，这种增加恢复到对照水平。静脉注射1mg/kg托非索泮可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。此外，脑室内注射0.1mg/kg托非索泮也显示出这些抑制作用。从这些结果可以得出结论，托非索泮可以恢复应激加载诱导的自主神经异常，并通过作用于调节自主神经功能的脑区下丘脑发挥这种作用。
