Antitussive effects of mu- and kappa-agonists in diabetic rats.
We evaluated the antitussive effect of morphine and U-50,488 in diabetic and non-diabetic rats. The antitussive potency of morphine (0.3 mg/kg, i.p.) in diabetic rats was significantly reduced as compared to the results in non-diabetic rats. The antitussive effect of U-50,488, a kappa-agonist, was also significantly lower in diabetic rats than in non-diabetic rats. When naltrindole (0.03 mg/kg, i.p.), a delta-antagonist, was administered 15 min before morphine or U-50,488, there was no difference between the antitussive potencies of these two opioid agonists in non-diabetic rats and in diabetic rats. Furthermore, naltrindole produces a reduction of the number of coughs in diabetic rats, but not in non-diabetic rats. It is possible that the enhancement of the antitussive potency of morphine and U-50,488 in naltrindole-treated diabetic rats is the result of the antitussive synergy produced by these opioid agonists and naltrindole. It seems likely, therefore, that delta-receptor-mediated endogenous inhibitory systems in mu- and kappa-receptor-mediated antitussive processes may be activated under diabetic conditions.
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Hoshi University, Tokyo, Japan.
J
J
Kamei
Y
Y
Iwamoto
T
T
Suzuki
M
M
Misawa
H
H
Nagase
Y
Y
Kasuya
D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D000700:Analgesics / Q000494:pharmacology; D000818:Animals; D000996:Antitussive Agents / Q000494:pharmacology*; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D008297:Male; D009020:Morphine / Q000494:pharmacology; D009271:Naltrexone / Q000031:analogs & derivatives / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D011759:Pyrrolidines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017473:Receptors, Opioid, kappa / Q000187:drug effects*; D017450:Receptors, Opioid, mu / Q000187:drug effects*
D000700:Analgesics; D000996:Antitussive Agents; D009292:Narcotic Antagonists; D011759:Pyrrolidines; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; D009271:Naltrexone; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D009020:Morphine; C055382:naltrindole