Synthesis and biological evaluation of novel dimiracetam derivatives useful for the treatment of neuropathic pain

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• 作者：Carlo Farina ; Stefania Gagliardi ; Carla Ghelardini ; Marisa Martinelli ; Monica Norcini ; Carlo Parini ; Paola Petrillo ; Silvano Ronzoni
• 关键词：Neuropathic pain ; CCI ; Streptozocin ; Nootropic drugs
• 刊名：Bioorganic and Medicinal Chemistry
• 出版年：2008
• 出版时间：15 March 2008
• 年：2008
• 卷：16
• 期：6
• 页码：3224-3232
• 全文大小：277 K

文摘

Chemical modifications of dimiracetam, a bicyclic analogue of the nootropic drug piracetam, afforded a small set of novel derivatives that were investigated in in vivo models of neuropathic pain. Compounds 5, 7 and 8 displayed a very promising antihyperalgesic profile in rat models of neuropathic pain induced by both chronic constriction injury of the sciatic nerve and streptozotocin. The compounds completely reverted the reduction of pain threshold evaluated by the paw pressure test. Importantly these derivatives did not induce any behavioural impairment as evaluated by the rotarod test. These results suggest that compounds 5, 7 and 8 might represent novel and well-tolerated therapeutic agents for the relief of neuropathic pain.