The abilities of specific kappa-opioid agonists, U-50,488H and U-62,066E, to cause antitussive tolerance were lower than that of morphine.
We examined whether the chronic administration of selective kappa-opioid agonists could produce antitussive tolerance, in a comparison with the mu-opioid morphine. A certain degree of tolerance to the antitussive effects of morphine appeared in rats treated chronically with this drug. However, chronic administration of U-50,488H and U-62,066E, highly selective agonists for the kappa-opioid receptor, does not result in the development of tolerance to their respective antitussive effects. These results suggest that the ability of kappa-opioid agonists to cause tolerance to their respective antitussive effects was lower than that of a mu-opioid agonist.
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; D000818:Animals; D000996:Antitussive Agents / Q000494:pharmacology*; D001665:Binding Sites; D001933:Brain Stem / Q000378:metabolism; D004361:Drug Tolerance; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D011759:Pyrrolidines / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011985:Receptors, Serotonin / Q000187:drug effects / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism
D000996:Antitussive Agents; D011759:Pyrrolidines; D011985:Receptors, Serotonin; D012701:Serotonin; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D009020:Morphine; C051272:spiradoline