کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
6283195 | 1615153 | 2013 | 5 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
The KV7.2/3 preferring channel opener ICA 27243 attenuates L-DOPA-induced dyskinesia in hemiparkinsonian rats
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موضوعات مرتبط
علوم زیستی و بیوفناوری
علم عصب شناسی
علوم اعصاب (عمومی)
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چکیده انگلیسی
Spontaneous involuntary dystonic and choreatic movements induced by L-DOPA (L-DOPA-induced dyskinesias (LID)) represent a severe complication of long-time pharmacotherapy in Parkinson's disease that deserves novel therapeutics. Previous studies demonstrated antidyskinetics effect of the KV7.2-7.5 channel opener retigabine after acute and chronic treatment in a rat model of LID. We hypothesized that this effect was mainly mediated by KV7.2/3 channels located on striatal projection neurons, as an increased activity of these neurons seems to be involved in the pathophysiology of LID. We therefore examined the acute effects of the KV7.2/3 preferring channel opener ICA 27243 (N-(6-chloro-pyridin-3-yl)-3,4-difluoro-benzamide, 5-15Â mg/kg i.p.) on LID in this animal model. Ten and 15Â mg ICA 27243 significantly reduced abnormal involuntary movements (AIM) while no negative impact on the antiparkinsonian effect of L-DOPA was observed. However, at the end of the testing session (180Â min) AIM scores increased after application of both doses. Further studies have to clarify if this can be avoided by a different application regime. Nevertheless, the present results suggest that selective openers of KV7.2/3 channels might be interesting candidates for the treatment of LID as antidyskinetic effects occurred at well-tolerated doses and did not interfere with the antiparkinsonian effect of L-DOPA.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neuroscience Letters - Volume 545, 17 June 2013, Pages 59-63
Journal: Neuroscience Letters - Volume 545, 17 June 2013, Pages 59-63
نویسندگان
Svenja E. Sander, Catherine Lambrecht, Angelika Richter,