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. 1994 Jan 14;251(2-3):291-4. doi: 10.1016/0014-2999(94)90411-1.
The effects of 7-benzylidenenaltrexone (BNTX), a selective delta 1-opioid receptor antagonist, and naltriben, a selective delta 2-opioid receptor antagonist, on the capsaicin-induced cough reflex were studied in mice. I.p. administration of BNTX in doses from 0.1 to 3.0 mg/kg reduced the number of coughs dose dependently. The antitussive effect of BNTX was antagonized by [D-Pen2,5]enkephalin (DPDPE), a selective delta 1-opioid receptor agonist, while [D-Ala2]deltorphin II, a selective delta 2-opioid receptor agonist, had no effect on the antitussive effect of BNTX. Pretreatment with nor-binaltorphimine, a selective kappa-opioid receptor antagonist, had no significant effect on the antitussive effect of BNTX. I.p. administration of naltriben, in doses of 1 and 3 mg/kg, also significantly decreased the number of coughs. Although the antitussive effect of naltriben was antagonized by nor-binaltorphimine, the antitussive effect of naltriben was not attenuated by either DPDPE or [D-Ala2]deltorphin II. The antitussive effects of neither BNTX nor naltriben were antagonized by beta-funaltrexamine, a selective mu-opioid receptor antagonist. Thus, it seems likely that the delta 1-opioid receptor antagonism may be involved in the antitussive effect of delta-opioid receptor antagonists.
在小鼠中研究了选择性δ1阿片受体拮抗剂7-苄叉基纳曲酮（BNTX）和选择性δ2阿片受体拮抗剂纳曲本对辣椒素诱导的咳嗽反射的影响。腹腔注射剂量为0.1至3.0mg/kg的BNTX可剂量依赖性地减少咳嗽次数。BNTX的镇咳作用被选择性δ1阿片受体激动剂[D- Pen2,5]脑啡肽（DPDPE）拮抗，而选择性δ2阿片受体激动剂[D- Ala2]强啡肽II对BNTX的镇咳作用无影响。用选择性κ阿片受体拮抗剂去甲二丙诺啡预处理对BNTX的镇咳作用无显著影响。腹腔注射剂量为1和3mg/kg的纳曲本也显著减少咳嗽次数。虽然纳曲本的镇咳作用被去甲二丙诺啡拮抗，但纳曲本的镇咳作用既不被DPDPE也不被[D- Ala2]强啡肽II减弱。选择性μ阿片受体拮抗剂β-氟纳曲胺对BNTX和纳曲本的镇咳作用均无拮抗作用。因此，δ1阿片受体拮抗作用可能参与了δ阿片受体拮抗剂的镇咳作用。
