Fachbereich Veterinärmedizin


Service-Navigation

    Publikationsdatenbank

    Kv7 (KCNQ) potassium channel openers attenuate levodopa-induced dyskinesias in 6-OHDA-lesioned rats (2007)

    Art
    Poster
    Autoren
    Sander, S. E.
    Richter, A.
    Kongress
    Annual Meeting of the Society for Neuroscience
    San Diego/USA, 03. – 07.11.2007
    Quelle
    Sprache
    Englisch
    Kontakt
    Institut für Pharmakologie und Toxikologie

    Koserstr. 20
    14195 Berlin
    Tel.+49 30 838 53221 Fax.+49 30 838 53112
    email:pharmakologie@vetmed.fu-berlin.de

    Abstract / Zusammenfassung

    Levodopa-induced dyskinesias (LID) represent a severe complication of long-time pharmacotherapy in Parkinson?s disease that deserves novel therapeutics. Activation of KV7.2-7.5 channels, which are expressed of striatal projection neurons, can decrease neuronal activity. Since overactivity of striatal projection neurons plays a key role in the pathophysiology of LID, in the present study the effects of the KV7.2-7.5 channel openers retigabine and flupirtine were examined in comparison to amantadine (positive control) in a rat model of LID.
    For drug testing, retigabine and flupirtine were administered prior to levodopa. In comparison to vehicle controls, retigabine (2.5 and 5 mg/kg i.p.) and flupirtine (5 and 10 mg/kg i.p.) significantly reduced the severity of dyskinesia. Apart from an initial pronounced ataxia after the application of 10 mg/kg flupirtine, the antidyskinetic effects were not accompanied by severe adverse effects and were comparable to those of amantadine. The KV7.2-7.5 channel blocker XE-991 (10,10-bis(4-pyridinylmethyl)-9(10H)-anthracenone) did not exert any effects on dyskinesia at a dose of 1.5 mg/kg i.p., but antagonized the antidyskinetic effects of retigabine. At a higher dose of 3 mg/kg, XE-991 increased the dystonic component.
    The results of our study suggest that the KV7 channel openers retigabine and flupirtine, could represent interesting candidates for the treatment of LID. In addition to antidyskinetic effects, the well-known analgetic effects of Kv7 channel openers are of advantage against painful muscle spasms in LID and as shown for flupirtine these compounds might exert antiparkinsonian and neuroprotective effects. Further studies are under the way to clarify whether retigabine and flupirtine delay or prevent the development of levodopa-induced dyskinesias