Yasumitsu R, Hirayama Y, Imai T, Miyayasu K, Hiroi J
Pharmacological Research Laboratories, Fujisawa Pharmaceutical Co., Ltd., Osaka, Japan.
Eur J Pharmacol. 1996 Apr 11;300(3):215-9. doi: 10.1016/0014-2999(95)00881-0.
We compared the effects of a tachykinin NK1 receptor antagonist, FK888 (N2-[(4R)-4-hydroxy-1-(1-methyl-1H-indol-3-yl)carbonyl-L-prolyl]-N-methy l-N -phenylmethyl-3-(2-naphthyl)-L-alaninamide), and a tachykinin NK2 receptor antagonist, SR48968 ((S)-N-methyl-N[4-(4-acetylamino-4-phenyl piperidino)-2-(3,4-dichlorophenyl)butyl]benzamide]), on citric acid-induced cough and bronchoconstriction in conscious guinea pigs. FK888 and SR48968 inhibited the cough dose dependently. Combination of FK888 and SR48968 showed a small additive effect compared with that of FK888 or SR48968 alone. SR48968 but not FK888 inhibited the bronchoconstriction dose dependently. These results indicate that tachykinin NK1 receptors as well as tachykinin NK2 receptors are involved in the citric acid-induced cough response. The antitussive activity of the tachykinin NK1 receptor antagonist appeared not to depend on the anti-bronchoconstrictor effects.
我们比较了速激肽NK1受体拮抗剂FK888（N2-[(4R)-4-羟基-1-(1-甲基-1H-吲哚-3-基)羰基-L-脯氨酰]-N-甲基-N-苯基甲基-3-(2-萘基)-L-丙氨酰胺）和速激肽NK2受体拮抗剂SR48968（(S)-N-甲基-N-[4-(4-乙酰氨基-4-苯基哌啶基)-2-(3,4-二氯苯基)丁基]苯甲酰胺）对清醒豚鼠柠檬酸诱发咳嗽和支气管收缩的影响。FK888和SR48968均剂量依赖性地抑制咳嗽。与单独使用FK888或SR48968相比，FK888和SR48968联合使用显示出较小的相加作用。SR48968剂量依赖性地抑制支气管收缩，而FK888则无此作用。这些结果表明，速激肽NK1受体以及速激肽NK2受体均参与柠檬酸诱发的咳嗽反应。速激肽NK1受体拮抗剂的镇咳活性似乎不依赖于抗支气管收缩作用。
