McLeod R L, Parra L E, Mutter J C, Erickson C H, Carey G J, Tulshian D B, Fawzi A B, Smith-Torhan A, Egan R W, Cuss F M, Hey J A
Allergy, Schering-Plough Research Institute, Kenilworth, New Jersey, NJ 07033-0539, USA.
Br J Pharmacol. 2001 Mar;132(6):1175-8. doi: 10.1038/sj.bjp.0703954.
We studied the central and peripheral antitussive effect of ORL(1) receptor activation with nociceptin/orphanin FQ in conscious guinea-pigs. In guinea-pig cough studies, nociceptin/orphanin FQ (10, 30, and 90 microg) given directly into the CNS by an intracerebroventricular (i.c.v.) route inhibited cough elicited by capsaicin exposure by approximately 23, 29 and 52%, respectively. The antitussive activity of nociceptin/orphanin FQ (90 microg, i.c.v.) was blocked by the selective ORL(1) antagonist [Phe(1)gamma(CH(2)-NH)Gly(2)]nociceptin-(1-13)-NH(2) (180 microg, i.c.v.) and J113397 (10 mg kg(-1), i.p.) but not by the opioid antagonist, naltrexone (3 mg kg(-1), i.p.). Furthermore, intravenous (i.v.) nociceptin/orphanin FQ (1.0 and 3.0 mg kg(-1)) also inhibited cough approximately by 25 and 42%, respectively. These findings indicate that selective ORL(1) agonists display the potential to inhibit cough by both a central and peripheral mechanism, and potentially represent a novel therapeutic approach for the treatment of cough.
我们研究了在清醒豚鼠中，通过孤啡肽/痛敏肽激活ORL(1)受体的中枢和外周镇咳作用。在豚鼠咳嗽研究中，通过脑室内（i.c.v.）途径直接将孤啡肽/痛敏肽（10、30和90微克）注入中枢神经系统，分别抑制辣椒素诱发咳嗽约23%、29%和52%。孤啡肽/痛敏肽（90微克，i.c.v.）的镇咳活性被选择性ORL(1)拮抗剂[Phe(1)γ(CH(2)-NH)Gly(2)]孤啡肽-(1-13)-NH(2)（180微克，i.c.v.）和J113397（10毫克·千克(-1)，腹腔注射）阻断，但未被阿片类拮抗剂纳曲酮（3毫克·千克(-1)，腹腔注射）阻断。此外，静脉注射（i.v.）孤啡肽/痛敏肽（1.0和3.0毫克·千克(-1)）也分别抑制咳嗽约25%和42%。这些发现表明，选择性ORL(1)激动剂具有通过中枢和外周机制抑制咳嗽的潜力，可能代表一种治疗咳嗽的新方法。
