Nociceptin inhibits cough in the guinea-pig by activation of ORL(1) receptors.
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.
Allergy, Schering-Plough Research Institute, Kenilworth, New Jersey, NJ 07033-0539, USA. robbie.mcleod@spcorp.com
R L
RL
McLeod
L E
LE
Parra
J C
JC
Mutter
C H
CH
Erickson
G J
GJ
Carey
D B
DB
Tulshian
A B
AB
Fawzi
A
A
Smith-Torhan
R W
RW
Egan
F M
FM
Cuss
J A
JA
Hey
D000818:Animals; D000996:Antitussive Agents / Q000627:therapeutic use*; D016466:CHO Cells; D002211:Capsaicin; D003371:Cough / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D006224:Cricetinae; D004195:Disease Models, Animal; D006168:Guinea Pigs; D008297:Male; D018847:Opioid Peptides / Q000627:therapeutic use*; D011957:Receptors, Opioid / Q000187:drug effects / Q000378:metabolism*; D000094942:Nociceptin Receptor; D000097629:Nociceptin
D000996:Antitussive Agents; D002211:Capsaicin; D018847:Opioid Peptides; D011957:Receptors, Opioid; D000094942:Nociceptin Receptor; D000097629:Nociceptin