کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8998182 | 1115607 | 2005 | 11 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Efficacy of antiepileptic tetramethylcyclopropyl analogues of valproic acid amides in a rat model of neuropathic pain
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کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
علم عصب شناسی
علوم اعصاب رفتاری
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چکیده انگلیسی
Antiepileptic drugs (AEDs) are widely utilized in the management of neuropathic pain. The AED valproic acid (VPA) holds out particular promise as it engages a variety of different anticonvulsant mechanisms simultaneously. However, the clinical use of VPA is limited by two rare but potentially life-threatening side effects: teratogenicity and hepatotoxicity. We have synthesized several tetramethylcyclopropyl analogues of VPA amides that are non-teratogenic, and are likely to be non-hepatotoxic, and that exhibit good antiepileptic efficacy. In the present study we have assessed the antiallodynic activity of these compounds in comparison to VPA and gabapentin (GBP) using the rat spinal nerve ligation (SNL) model of neuropathic pain. TMCA (2,2,3,3-tetramethylcyclopropanecarboxylic acid, 100-250Â mg/kg), TMCD (2,2,3,3-tetramethylcyclopropanecarboxamide, 40-150Â mg/kg), MTMCD (N-methyl-TMCD, 20-100Â mg/kg), and TMCU (2,2,3,3-tetramethylcyclopropanecarbonylurea, 40-240Â mg/kg) all showed dose-related reversal of tactile allodynia, with ED50 values of 181, 85, 41, and 171Â mg/kg i.p., respectively. All were more potent than VPA (ED50Â =Â 269Â mg/kg). An antiallodynic effect was obtained for TMCD, MTMCD and TMCU at plasma concentrations as low as 23, 6 and 22Â mg/L, respectively. MTMCD was found to be non-toxic, non-sedative and equipotent to gabapentin, currently the leading AED in neuropathic pain treatment. Tetramethylcyclopropyl analogues of VPA amides have potential to become a new series of drugs for neuropathic pain treatment.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neuropharmacology - Volume 49, Issue 8, December 2005, Pages 1110-1120
Journal: Neuropharmacology - Volume 49, Issue 8, December 2005, Pages 1110-1120
نویسندگان
Ilan Winkler, Eyal Sobol, Boris Yagen, Amir Steinman, Marshall Devor, Meir Bialer,