Antianalgesia: Stereoselective Action of dextro-Morphine over levo-Morphine on Glia in the Mouse Spinal Cord
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,...
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Published in | The Journal of pharmacology and experimental therapeutics Vol. 314; no. 3; pp. 1101 - 1108 |
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Main Authors | , , , , |
Format | Journal Article |
Language | English |
Published |
United States
American Society for Pharmacology and Experimental Therapeutics
01.09.2005
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Subjects | |
Online Access | Get full text |
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Summary: | 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 (0.3â33 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 ED 50 value for dextro -morphine to induce antianalgesia was estimated to be 1.07 fmol, which is 71,000-fold more potent than the ED 50 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 (3.3â65 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. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
ISSN: | 0022-3565 1521-0103 |
DOI: | 10.1124/jpet.105.087130 |