Kamei J, Iwamoto Y, Suzuki T, Misawa M, Nagase H, Kasuya Y
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Hoshi University, Tokyo, Japan.
Eur J Pharmacol. 1993 Nov 9;249(2):161-5. doi: 10.1016/0014-2999(93)90428-k.
The effects of naltrindole, a selective delta-opioid receptor antagonist, on the capsaicin-induced cough reflex in mice and rats were studied. Intraperitoneal administration of naltrindole decreased the number of coughs both in mice and rats dose dependently. The cough-depressant effects reached a peak 15 min after the administration of naltrindole and lasted more than 120 min. Pretreatment with [D-Pen2,D-Pen5]enkephalin, a selective delta-opioid receptor agonist, partially but significantly reduced the antitussive effect of naltrindole. Blockade of kappa-opioid receptors by pretreatment with nor-binaltorphimine also partially antagonized the antitussive effect of naltrindole. However, the antitussive effect of naltrindole was not antagonized by beta-funaltrexamine, a selective mu-opioid receptor antagonist. Thus, it is possible that the antitussive effect of naltrindole may be mediated, in part, by kappa-opioid receptors. The present results provide evidence for the development of delta-opioid antagonists, especially naltrindole, for use as antitussive drugs.
研究了选择性δ-阿片受体拮抗剂纳曲吲哚对辣椒素诱导的小鼠和大鼠咳嗽反射的影响。腹腔注射纳曲吲哚可使小鼠和大鼠的咳嗽次数剂量依赖性减少。纳曲吲哚给药后15分钟咳嗽抑制作用达到峰值，并持续超过120分钟。用选择性δ-阿片受体激动剂[D-青霉胺2，D-青霉胺5]脑啡肽预处理可部分但显著降低纳曲吲哚的镇咳作用。用去甲二氢吗啡酮预处理阻断κ-阿片受体也可部分拮抗纳曲吲哚的镇咳作用。然而，选择性μ-阿片受体拮抗剂β-芬太尼并不拮抗纳曲吲哚的镇咳作用。因此，纳曲吲哚的镇咳作用可能部分由κ-阿片受体介导。目前的结果为开发δ-阿片拮抗剂，尤其是纳曲吲哚作为镇咳药物提供了证据。
