Morita K, Kamei J
Department of Pathophysiology and Therapeutics, Faculty of Pharmaceutical Sciences, Hoshi University, 4-41, Ebara 2-chome, Shinagawa-ku, Tokyo, Japan.
Eur J Pharmacol. 2000 Apr 28;395(2):161-4. doi: 10.1016/s0014-2999(00)00197-7.
The effect of glibenclamide, an ATP-sensitive K(+) channel blocker, on the anti-tussive effect of moguisteine and of pinacidil, an ATP-sensitive K(+) channel opener in guinea pigs was studied. Pinacidil (1 and 5 mg/kg, subcutaneous (s.c.)) dose-dependently reduced the number of coughs. The anti-tussive effect of pinacidil was significantly and dose-dependently antagonized by pre-treatment with glibenclamide (3 and 10 mg/kg, i.p.). Moguisteine (1 and 5 mg/kg, s.c.) dose-dependently reduced the number of coughs. The anti-tussive effect of moguisteine was also reduced by pre-treatment with glibenclamide, in a dose-dependent manner. However, pre-treatment with glibenclamide had no effect on the anti-tussive effects of dihydrocodeine and dextromethorphan. Glibenclamide (10 mg/kg, i.p.), by itself, had no significant effect on the number of coughs. These results suggest that pinacidil and moguisteine may exert their anti-tussive effects through the activation of ATP-sensitive K(+) channels. Furthermore, it is possible that ATP-sensitive K(+) channels may be involved in the anti-tussive effect of peripherally acting non-narcotic anti-tussive drugs.
研究了ATP敏感性钾通道阻滞剂格列本脲对豚鼠中莫吉司坦和ATP敏感性钾通道开放剂吡那地尔镇咳作用的影响。吡那地尔（1和5毫克/千克，皮下注射）剂量依赖性地减少咳嗽次数。预先给予格列本脲（3和10毫克/千克，腹腔注射）可显著且剂量依赖性地拮抗吡那地尔的镇咳作用。莫吉司坦（1和5毫克/千克，皮下注射）剂量依赖性地减少咳嗽次数。预先给予格列本脲也以剂量依赖的方式降低了莫吉司坦的镇咳作用。然而，预先给予格列本脲对二氢可待因和右美沙芬的镇咳作用没有影响。格列本脲（10毫克/千克，腹腔注射）本身对咳嗽次数没有显著影响。这些结果表明，吡那地尔和莫吉司坦可能通过激活ATP敏感性钾通道发挥其镇咳作用。此外，ATP敏感性钾通道可能参与外周作用的非麻醉性镇咳药的镇咳作用。
