Agonist/antagonist properties of nalbuphine, butorphanol and (-)-pentazocine in male vs. female rats.
To determine whether sex differences in the effects of mixed-action opioids could be due to differential activity at mu or kappa receptors, agonist/antagonist properties of nalbuphine, butorphanol and (-)-pentazocine were compared in male vs. female rats using a diuresis test. In water-loaded rats (2-h test), nalbuphine and (-)-pentazocine dose-dependently increased urination similarly in both sexes, whereas butorphanol increased urination more in females than in males on a ml/kg basis. The diuretic effects of all three opioids were at least partially blocked by the kappa receptor-selective antagonist nor-binaltorphimine (nor-BNI, 5 mg/kg) in both sexes. Kappa receptor-mediated antagonism of diuresis induced by U69,593 (0.56 mg/kg) was only observed with butorphanol in males. In water-loaded rats (1-h test), nalbuphine did not suppress, and butorphanol and (-)-pentazocine significantly suppressed urination in males only; all three mixed-action opioids dose-dependently blocked the antidiuretic effect of the selective mu agonist fentanyl (0.056 mg/kg) in both sexes. The ability of nalbuphine and (-)-pentazocine to block fentanyl-induced antidiuresis was not affected by pretreatment with nor-BNI in either sex. In contrast, the ability of butorphanol to block fentanyl-induced antidiuresis was attenuated by pretreatment with nor-BNI in males but not in females. These results suggest that sex differences in the effects of these mixed-action opioids are primarily due to their greater relative efficacy at the mu receptor in male than in female rats; butorphanol also may have greater efficacy at kappa receptors in females than in males.
Craft
R M
RM
Department of Psychology, Washington State University, CB 644820, Pullman, WA 99164-4820, USA. craft@wsu.edu
McNiel
D M
DM
D000818:Animals; D044482:Benzeneacetamides / Q000494:pharmacology; D002077:Butorphanol / Q000494:pharmacology*; D004231:Diuresis / Q000187:drug effects; D004232:Diuretics / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D008297:Male; D009266:Nalbuphine / Q000494:pharmacology*; D009271:Naltrexone / Q000031:analogs & derivatives* / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology*; D010423:Pentazocine / Q000494:pharmacology*; D011759:Pyrrolidines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017473:Receptors, Opioid, kappa / Q000819:agonists* / Q000037:antagonists & inhibitors*; D017450:Receptors, Opioid, mu / Q000819:agonists* / Q000037:antagonists & inhibitors*; D012727:Sex Characteristics; D014554:Urination / Q000187:drug effects
D044482:Benzeneacetamides; D004232:Diuretics; D009292:Narcotic Antagonists; D011759:Pyrrolidines; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; C051844:norbinaltorphimine; D009271:Naltrexone; C024524:beta-funaltrexamine; C045444:U 69593; D009266:Nalbuphine; D002077:Butorphanol; D010423:Pentazocine