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Research ArticleNEUROPHARMACOLOGY

Antianalgesia: Stereoselective Action of dextro-Morphine over levo-Morphine on Glia in the Mouse Spinal Cord

Hsiang-En Wu, Jonathan Thompson, Han-Sen Sun, Maia Terashvili and Leon F. Tseng
Journal of Pharmacology and Experimental Therapeutics September 2005, 314 (3) 1101-1108; DOI: https://doi.org/10.1124/jpet.105.087130
Hsiang-En Wu
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Jonathan Thompson
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Han-Sen Sun
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Maia Terashvili
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Leon F. Tseng
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Abstract

We have previously shown that the naturally occurring levo-morphine at a subanalgesic picomolar dose pretreated i.t. induces antianalgesia against levo-morphine-produced antinociception. We now report that the synthetic stereo-enantiomer dextro-morphine, even at an extremely low femtomolar dose, induces antianalgesia against levo-morphine-produced antinociception using the tail-flick (TF) test in male CD-1 mice. Intrathecal pretreatment with dextro-morphine (33 fmol) time-dependently attenuated the i.t. levo-morphine-produced TF inhibition for 4 h and returned to the preinjection control level at 24 h. Intrathecal pretreatment with dextro-morphine (0.3–33 fmol), which injected alone did not affect the baseline TF latency, dose-dependently attenuated the TF inhibition produced by i.t.-administered levo-morphine (3.0 nmol). The ED50 value for dextro-morphine to induce antianalgesia was estimated to be 1.07 fmol, which is 71,000-fold more potent than the ED50 value of levo-morphine, indicating the high stereoselective action of dextro-morphine over levo-morphine for the induction of antianalgesia. Like levo-morphine, the dextro-morphine-induced antianalgesia against levo-morphine-produced TF inhibition was dose-dependently blocked by the nonopioid dextro-naloxone and its stereo-enantiomer levo-naloxone, a nonselective μ-opioid receptor antagonist. The antianalgesia induced by levo-morphine and dextro-morphine is reversed by the pretreatment with the glial inhibitor propentofylline (3.3–65 nmol), indicating that the antianalgesia is mediated by glial stimulation. The findings strongly indicate that the antianalgesia induced by levo-morphine and dextro-morphine is mediated by the stimulation of a novel nonopioid receptor on glial cells.

Footnotes

  • This work was supported by Grant DA12588 from the National Institutes of Health, National Institute on Drug Abuse (to L.F.T.).

  • doi:10.1124/jpet.105.087130.

  • ABBREVIATIONS: TF, tail-flick; ANOVA, analysis of variance; CI, confidence interval.

    • Received March 30, 2005.
    • Accepted May 12, 2005.
  • The American Society for Pharmacology and Experimental Therapeutics
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Journal of Pharmacology and Experimental Therapeutics: 377 (2)
Journal of Pharmacology and Experimental Therapeutics
Vol. 377, Issue 2
1 May 2021
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Research ArticleNEUROPHARMACOLOGY

Antianalgesia: Stereoselective Action of dextro-Morphine over levo-Morphine on Glia in the Mouse Spinal Cord

Hsiang-En Wu, Jonathan Thompson, Han-Sen Sun, Maia Terashvili and Leon F. Tseng
Journal of Pharmacology and Experimental Therapeutics September 1, 2005, 314 (3) 1101-1108; DOI: https://doi.org/10.1124/jpet.105.087130

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Research ArticleNEUROPHARMACOLOGY

Antianalgesia: Stereoselective Action of dextro-Morphine over levo-Morphine on Glia in the Mouse Spinal Cord

Hsiang-En Wu, Jonathan Thompson, Han-Sen Sun, Maia Terashvili and Leon F. Tseng
Journal of Pharmacology and Experimental Therapeutics September 1, 2005, 314 (3) 1101-1108; DOI: https://doi.org/10.1124/jpet.105.087130
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