Antitussive effects of two specific kappa-opioid agonists, U-50,488H and U-62,066E, in rats.
The effects of highly selective agonists of kappa-opioid receptors, namely U-50,488H and U-62,066E, on the capsaicin-induced cough reflex in rats were studied. Intracisternal (i.cist.) injection of U-50,488H and of U-62,066E significantly decreased the number of coughs in a dose-dependent manner. The antitussive potency of i.cist. injection of these two kappa-opioid agonists was similar to that of morphine. Intraperitoneal (i.p.) injection of U-50,488H and of U-62,066E also decreased the number of coughs, again in a dose-dependent manner. The antitussive effects of U-50,488H and U-62,066E were blocked by norbinaltorphimine, an antagonist of kappa-opioid receptors. Methysergide, administered i.cist. (3 nmol), antagonized the antitussive effects of U-50,488H and U-62,066E. However, ketanserin had no effect on the antitussive effects of these kappa-opioid agonists. These data suggest that U-50,488H and U-62,066E exert their antitussive effect on rats through stimulation of kappa-opioid receptors. Furthermore, with respect to the antitussive effects of kappa-opioid agonists, the system that involves 5-HT1 receptors may be more important than the system that involves 5-HT2 receptors.
Kamei
J
J
Department of Pharmacology, School of Pharmacy, Hoshi University, Tokyo, Japan.
Tanihara
H
H
Kasuya
Y
Y
D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D000996:Antitussive Agents; D002946:Cisterna Magna; D003371:Cough / Q000503:physiopathology*; D007267:Injections; D007650:Ketanserin / Q000494:pharmacology; D008297:Male; D008784:Methysergide / Q000494:pharmacology; D009020:Morphine / Q000494:pharmacology; D009270:Naloxone / Q000494:pharmacology; D009271:Naltrexone / Q000031:analogs & derivatives / Q000494:pharmacology; D011759:Pyrrolidines / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012018:Reflex / Q000187:drug effects*
D000700:Analgesics; D000996:Antitussive Agents; D011759:Pyrrolidines; D009270:Naloxone; C051844:norbinaltorphimine; D009271:Naltrexone; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D009020:Morphine; D007650:Ketanserin; C051272:spiradoline; D008784:Methysergide