Ishii R, Furuta M, Hashimoto M, Naruse T, Gallico L, Ceserani R
Research and Development Laboratories, Maruho, Kyoto, Japan.
Eur J Pharmacol. 1998 Dec 4;362(2-3):207-12. doi: 10.1016/s0014-2999(98)00760-2.
The study aimed to further demonstrate the peripheral antitussive properties of moguisteine. Firstly, the antitussive effect of moguisteine on the cough reflex induced by inhalation of citric acid aerosol was evaluated in conscious guinea pigs. Secondly, the effects of both moguisteine and codeine on the centrally mediated cough reflex induced by afferent electrical stimulation of the superior laryngeal nerve were investigated in anesthetized guinea pigs. Moguisteine (2.5-10 mg/kg, intravenously, i.v.) reduced the cough reflex induced by 7.5% citric acid aerosol in a dose-dependent manner, with an ED50 value of 0.55 mg/kg. Both i.v. (0.5-4 mg/kg) and intracerebroventricular (i.c.v., 5-20 microg) injection of codeine dose dependently inhibited the cough reflex induced by afferent electrical stimulation of the superior laryngeal nerve; the ED50 values were 0.91 mg/kg and 7.90 microg, respectively. The inhibitory effect of codeine (4 mg/kg i.v.) was abolished by pretreatment with naloxone (2 mg/kg intraperitoneally). In contrast to codeine, neither i.v. (4 and 20 mg/kg) nor i.c.v. (20 microg) injection of moguisteine affected the cough reflex. These results suggest that the antitussive effect of codeine is mediated by central opioid mechanisms, whereas the antitussive effect of moguisteine is mediated by peripheral mechanisms.
该研究旨在进一步证明氨溴索的外周镇咳特性。首先，在清醒的豚鼠中评估了氨溴索对吸入柠檬酸气雾剂诱发的咳嗽反射的镇咳作用。其次，在麻醉的豚鼠中研究了氨溴索和可待因对经喉上神经传入电刺激诱发的中枢介导咳嗽反射的影响。氨溴索（2.5 - 10毫克/千克，静脉注射）以剂量依赖性方式减少了7.5%柠檬酸气雾剂诱发的咳嗽反射，ED50值为0.55毫克/千克。静脉注射（0.5 - 4毫克/千克）和脑室内注射（5 - 20微克）可待因均剂量依赖性地抑制了经喉上神经传入电刺激诱发的咳嗽反射；ED50值分别为0.91毫克/千克和7.90微克。用纳洛酮（2毫克/千克腹腔注射）预处理可消除可待因（4毫克/千克静脉注射）的抑制作用。与可待因相反，静脉注射（4和20毫克/千克）和脑室内注射（20微克）氨溴索均不影响咳嗽反射。这些结果表明，可待因的镇咳作用是由中枢阿片类机制介导的，但氨溴索的镇咳作用是由外周机制介导的。
