Involvement of delta 1-opioid receptor antagonism in the antitussive effect of delta-opioid receptor antagonists.
The effects of 7-benzylidenenaltrexone (BNTX), a selective delta 1-opioid receptor antagonist, and naltriben, a selective delta 2-opioid receptor antagonist, on the capsaicin-induced cough reflex were studied in mice. I.p. administration of BNTX in doses from 0.1 to 3.0 mg/kg reduced the number of coughs dose dependently. The antitussive effect of BNTX was antagonized by [D-Pen2,5]enkephalin (DPDPE), a selective delta 1-opioid receptor agonist, while [D-Ala2]deltorphin II, a selective delta 2-opioid receptor agonist, had no effect on the antitussive effect of BNTX. Pretreatment with nor-binaltorphimine, a selective kappa-opioid receptor antagonist, had no significant effect on the antitussive effect of BNTX. I.p. administration of naltriben, in doses of 1 and 3 mg/kg, also significantly decreased the number of coughs. Although the antitussive effect of naltriben was antagonized by nor-binaltorphimine, the antitussive effect of naltriben was not attenuated by either DPDPE or [D-Ala2]deltorphin II. The antitussive effects of neither BNTX nor naltriben were antagonized by beta-funaltrexamine, a selective mu-opioid receptor antagonist. Thus, it seems likely that the delta 1-opioid receptor antagonism may be involved in the antitussive effect of delta-opioid receptor antagonists.
Kamei
J
J
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Hoshi University, Tokyo, Japan.
Iwamoto
Y
Y
Suzuki
T
T
Misawa
M
M
Nagase
H
H
Kasuya
Y
Y
D000818:Animals; D000996:Antitussive Agents / Q000493:pharmacokinetics / Q000494:pharmacology*; D001597:Benzylidene Compounds / Q000493:pharmacokinetics / Q000494:pharmacology; D002211:Capsaicin; D003371:Cough / Q000139:chemically induced / Q000188:drug therapy; D004305:Dose-Response Relationship, Drug; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009271:Naltrexone / Q000031:analogs & derivatives / Q000493:pharmacokinetics / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000493:pharmacokinetics / Q000494:pharmacology; D017465:Receptors, Opioid, delta / Q000037:antagonists & inhibitors*
D000996:Antitussive Agents; D001597:Benzylidene Compounds; D009292:Narcotic Antagonists; D017465:Receptors, Opioid, delta; C068868:naltrindole benzofuran; C077358:7-benzylidenenaltrexone; D009271:Naltrexone; D002211:Capsaicin