Farina Carlo, Gagliardi Stefania, Ghelardini Carla, Martinelli Marisa, Norcini Monica, Parini Carlo, Petrillo Paola, Ronzoni Silvano
Brane Discovery, Insubrias Biopark, Via Lepetit 34, 21040 Gerenzano, Varese, Italy.
Bioorg Med Chem. 2008 Mar 15;16(6):3224-32. doi: 10.1016/j.bmc.2007.12.015. Epub 2007 Dec 15.
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.
双环类似物二甲拉西坦（一种益智药吡拉西坦的类似物）的化学修饰产生了一小类新型衍生物，这些衍生物在神经性疼痛的体内模型中进行了研究。化合物5、7和8在坐骨神经慢性压迫损伤和链脲佐菌素诱导的神经性疼痛大鼠模型中表现出非常有前景的抗痛觉过敏特征。这些化合物完全逆转了通过爪部压力测试评估的痛阈降低。重要的是，通过转棒试验评估，这些衍生物没有引起任何行为损伤。这些结果表明，化合物5、7和8可能代表用于缓解神经性疼痛的新型且耐受性良好的治疗剂。
