These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: The NMDA receptor antagonists, LY274614 and MK-801, and the nitric oxide synthase inhibitor, NG-nitro-L-arginine, attenuate analgesic tolerance to the mu-opioid morphine but not to kappa opioids.
    Author: Elliott K, Minami N, Kolesnikov YA, Pasternak GW, Inturrisi CE.
    Journal: Pain; 1994 Jan; 56(1):69-75. PubMed ID: 7512709.
    Abstract:
    Once daily s.c. administration of 5 mg/kg morphine, a mu-opioid agonist, or U50488H (U50), a kappa 1-opioid agonist, for 5 days in male CD-1 mice results in a 2-3-fold shift to the right of the respective analgesic (tail flick) dose-response curves, indicating the development of tolerance. Concurrent s.c. administration of the competitive NMDA receptor antagonist, LY274614 (LY), at 24 mg/kg/24 h infusion (osmotic pump) or 6 mg/kg i.p. once daily attenuates the development of morphine tolerance, when the response to saline plus morphine is compared on day 5 with LY plus morphine. Using this paradigm, once daily administration of either the non-competitive NMDA antagonist, MK-801, at 0.3 mg/kg i.p. or the nitric oxide synthase inhibitor, NG-nitro-L-arginine (NorArg), at 1 mg/kg i.p. twice daily attenuated the development of morphine tolerance. None of these drugs modify the tail-flick response or alter the ED50 for morphine. In contrast, co-administration of LY, MK-801 or NorArg, as above, failed to attenuate the development of tolerance to U50 or to the kappa 3-opioid agonist, naloxone benzoylhydrazone (NalBzoH). These results suggest that mu-opioid tolerance but not kappa 1- or kappa 3-opioid tolerance involves the mediation of NMDA receptors and the nitric oxide system.
    [Abstract] [Full Text] [Related] [New Search]