Fariello Ruggero G, Ghelardini Carla, Di Cesare Mannelli Lorenzo, Bonanno Giambattista, Pittaluga Anna, Milanese Marco, Misiano Paola, Farina Carlo
Neurotune AG, Wagistrasse 27a, CH-8952 Schlieren, Switzerland.
Department of Neurosciences, Psychology, Drug Research and Child Health, Section of Pharmacology and Toxicology, University of Florence, Viale Pieraccini 6, I-50139 Florence, Italy.
Neuropharmacology. 2014 Jun;81:85-94. doi: 10.1016/j.neuropharm.2014.01.029. Epub 2014 Jan 31.
Dimiracetam, a bicyclic 2-pyrrolidinone derivative originally developed as cognition enhancer, is a member of the nootropic family for which anecdotal efficacy in models of neuropathic pain has been reported. Its antineuropathic activity was evaluated in established models of neuropathic pain induced by nerve injury, chemotherapy or MIA-induced osteoarthritis. Acutely, dimiracetam was very effective in models of antiretroviral drug induced painful neuropathy, oxaliplatin-induced hyperalgesia and in the MIA-osteoarthritis. Chronic dimiracetam dosing in the MIA and ART- induced models completely reverted hyperalgesia back to the level of healthy controls. Once reached, the maximal effect was maintained despite dose diminution and increased inter-dose interval. The effect of the last dose outlasted dimiracetam half-life longer than 12 times. In synaptosomal preparations, dimiracetam counteracted the NMDA-induced release of glutamate with highest potency in the spinal cord, possibly via NMDA receptor isoforms containing pH-sensitive GluN1 and GluN2A subunits. Dimiracetam appears to be a promising and safe treatment for neuropathic pain conditions for which there are very limited therapeutic options.
二氢麦角酰胺，一种最初作为认知增强剂开发的双环2-吡咯烷酮衍生物，是促智药家族的一员，有报道称其在神经性疼痛模型中具有一定疗效。在由神经损伤、化疗或MIA诱导的骨关节炎所引发的已确立的神经性疼痛模型中，对其二氢麦角酰胺的抗神经性疼痛活性进行了评估。在急性情况下，二氢麦角酰胺在抗逆转录病毒药物诱导的疼痛性神经病变模型、奥沙利铂诱导的痛觉过敏模型以及MIA诱导的骨关节炎模型中非常有效。在MIA和ART诱导的模型中，长期给予二氢麦角酰胺可使痛觉过敏完全恢复到健康对照水平。一旦达到最大效果，尽管剂量减少且给药间隔时间延长，该效果仍能维持。最后一剂的效果持续时间超过二氢麦角酰胺半衰期达12倍以上。在突触体制剂中，二氢麦角酰胺可能通过含有pH敏感型GluN1和GluN2A亚基的NMDA受体亚型，在脊髓中以最高效力抵消NMDA诱导的谷氨酸释放。对于治疗选择非常有限的神经性疼痛病症，二氢麦角酰胺似乎是一种有前景且安全的治疗方法。
