• Acta Anaesthesiol Scand · Jul 2000

    The dissociation of sedative from spinal antinociceptive effects following administration of a novel alpha-2-adrenoceptor agonist, MPV-2426, in the locus coeruleus in the rat.

    • M Xu, H Wei, V K Kontinen, E Kalso, and A Pertovaara.
    • Department of Pharmacology and Toxicology, Institute of Biomedicine, University of Helsinki, Finland.
    • Acta Anaesthesiol Scand. 2000 Jul 1;44(6):648-55.

    BackgroundMPV-2426 is a novel alpha-2-adrenoceptor agonist developed for spinal pain therapy. In the present study we characterized its sedative and antinociceptive properties following microinjections into the brainstem and intrathecally at the lumbar spinal cord level.MethodsSedative effects of MPV-2426 were assessed in a locomotion measuring device following unilateral microinjection into the locus coeruleus (LC) of the brainstem or 1-2 mm rostral to the LC in rats. Antinociceptive effects induced by MPV-2426 in the brainstem, and for comparison intrathecally at the lumbar spinal cord level, were determined with a tail-flick test. Dexmedetomidine was used as the reference alpha-2-adrenoceptor agonist.ResultsMPV-2426 produced a dose-related hypolocomotive/sedative effect, which was significantly stronger following microinjection into the LC than 1-2 mm rostral to the LC. The sedation induced by MPV-2426 was reversed by atipamezole (1 mg/kg s.c.), an alpha-2-adrenoceptor antagonist. The sedative potency of dexmedetomidine, the reference alpha-2-adrenoceptor agonist, was stronger and less dependent on the exact injection site in the brainstem. Following microinjections at sedative doses in the brainstem, only dexmedetomidine produced a significant antinociceptive effect in the tail-flick test. When microinjected into the lumbar spinal cord, MPV-2426 and dexmedetomidine had an equally strong antinociceptive effect in the tail-flick test.ConclusionThe results indicate that the sedative potency of MPV-2426 is considerably weaker than that of dexmedetomidine. Additionally, the spread of MPV-2426 within the central nervous system is more limited than that of dexmedetomidine. This could explain why MPV-2426 is sedative only when injected into the LC while antinociceptive effect is obtained when it is injected intrathecally at the lumbar spinal cord level.

      Pubmed     Full text   Copy Citation     Plaintext  

      Add institutional full text...

    Notes

     
    Knowledge, pearl, summary or comment to share?
    300 characters remaining
    help        
    You can also include formatting, links, images and footnotes in your notes
    • Simple formatting can be added to notes, such as *italics*, _underline_ or **bold**.
    • Superscript can be denoted by <sup>text</sup> and subscript <sub>text</sub>.
    • Numbered or bulleted lists can be created using either numbered lines 1. 2. 3., hyphens - or asterisks *.
    • Links can be included with: [my link to pubmed](http://pubmed.com)
    • Images can be included with: ![alt text](https://bestmedicaljournal.com/study_graph.jpg "Image Title Text")
    • For footnotes use [^1](This is a footnote.) inline.
    • Or use an inline reference [^1] to refer to a longer footnote elseweher in the document [^1]: This is a long footnote..

    hide…