Involvement of mu-opioid receptors in the antitussive effects of pentazocine.
The effect of pentazocine on the capsaicin-induced cough reflex in rats was investigated. Intraperitoneal injection of pentazocine, in doses from 1 to 10 mg/kg, significantly decreased the number of coughs in a dose-dependent manner. The antitussive effect of pentazocine (10 mg/kg, i.p.) was significantly reduced by prior injection of naloxone (0.3 mg/kg, i.p.), but it was unaffected by Mr-2266 BS (5 mg/kg, i.p.), an antagonist of kappa-opioid receptors. The antinociceptive potency of pentazocine (30 mg/kg, i.p.), as determined by the formalin test, was significantly reduced by pretreatment with Mr-2266 BS (5 mg/kg, i.p.), whereas naloxone (0.3 mg/kg, i.p.) had no significant effect on the antinociceptive effect of pentazocine. The antitussive effects of pentazocine (3 mg/kg) and morphine (0.1 mg/kg) were significantly enhanced in rats treated chronically with naloxone (5 mg/kg/day, 5 days), whereas the antitussive effect of U-50,488 H (1 mg/kg, i.p.), a selective kappa-opioid agonist, was not enhanced in these rats. By contrast, the antinociceptive effect of morphine (0.01 mg/kg, i.p.) was significantly enhanced in rats that had been pretreated chronically with naloxone. However, the antinociceptive effects induced by pentazocine (3 mg/kg, i.p.) and U-50,488 H (1 mg/kg, i.p.) were unchanged. These results suggest that pentazocine-induced antitussive effects in rats are mediated via stimulation of mu-opioid receptors.
Kamei
J
J
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Hoshi University, Tokyo, Japan.
Katsuma
K
K
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 / Q000494:pharmacology*; D001575:Benzomorphans / Q000494:pharmacology; D002211:Capsaicin; D003371:Cough / Q000139:chemically induced / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D007274:Injections, Intraperitoneal; D007279:Injections, Subcutaneous; D008297:Male; D009020:Morphine / Q000037:antagonists & inhibitors / Q000494:pharmacology; D009270:Naloxone / Q000494:pharmacology; D010423:Pentazocine / Q000008:administration & dosage / Q000494:pharmacology*; D011759:Pyrrolidines / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011957:Receptors, Opioid / Q000187:drug effects* / Q000378:metabolism; D017450:Receptors, Opioid, mu
D000700:Analgesics; D000996:Antitussive Agents; D001575:Benzomorphans; D011759:Pyrrolidines; D011957:Receptors, Opioid; D017450:Receptors, Opioid, mu; D009270:Naloxone; C027247:MR 2266; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D009020:Morphine; D010423:Pentazocine; D002211:Capsaicin