title: Nalbuphine coadministered with morphine prevents tolerance and dependence.
abstract: Nalbuphine, an opioid mixed agonist-antagonist, prevents many morphine-related side effects. In this study, we compared the effects of nalbuphine versus naloxone on the prevention of morphine tolerance and dependence in Sprague-Dawley rats. Group 1 received a morphine 5 mg/kg intraperitoneal (I.P.) injection. Groups 2 and 3 received single doses of nalbuphine (0.01 to 5 mg/kg I.P.) or naloxone (1 to 500 microg/kg I.P.) coadministered with morphine (5 mg/kg I.P.), respectively. Group 4 received a saline I.P. injection. Treatments were continued for 4 days. The occurrence of tolerance was estimated by comparing the antinociceptive effect of morphine on Day 1 (Group 1) and Day 5 (each group). The severity of dependence was determined by precipitated withdrawal signs (incidence of diarrhea and teeth chattering) induced by naloxone (10 mg/kg I.P.). We found that coadministration of nalbuphine or naloxone with morphine dose-dependently blocked the development of morphine tolerance and dependence. However, unlike naloxone, nalbuphine did not attenuate the antinociceptive effect of morphine.
authors.affiliation: Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
authors.forename: S C
authors.initials: SC
authors.lastname: Lee
authors.forename: J J
authors.initials: JJ
authors.lastname: Wang
authors.forename: S T
authors.initials: ST
authors.lastname: Ho
authors.forename: P L
authors.initials: PL
authors.lastname: Tao
mesh_terms: D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D000701:Analgesics, Opioid / Q000008:administration & dosage*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D004361:Drug Tolerance; D008297:Male; D009020:Morphine / Q000008:administration & dosage*; D009266:Nalbuphine / Q000008:administration & dosage*; D009270:Naloxone / Q000008:administration & dosage; D009271:Naltrexone / Q000031:analogs & derivatives / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000008:administration & dosage*; D009293:Opioid-Related Disorders / Q000517:prevention & control*; D011759:Pyrrolidines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000701:Analgesics, Opioid; D009292:Narcotic Antagonists; D011759:Pyrrolidines; D009270:Naloxone; D009271:Naltrexone; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; C024524:beta-funaltrexamine; D009020:Morphine; D009266:Nalbuphine