Development of oxicam-bearing non-steroidal anti-inflammatory drugs with novel anti-parkinsonian mechanism.

本研究发现，三种含奥昔康的非甾体抗炎药（NSAIDs），如美洛昔康、吡罗西康和替诺昔康，具有新的神经保护机制，可维持磷脂酰肌醇3-激酶(PI3K)/Akt信号，对抗MPP^+诱导的神经母细胞瘤SH-SY5Y细胞毒性。在相同的实验中，其他类型的非甾体抗炎药没有显示出神经保护作用。在帕金森病的慢性小鼠模型中，美洛昔康通过维持akt信号传导改善运动功能障碍和多巴胺能神经变性。这些结果表明，美洛昔康可能是帕金森病的一种候选药物。

In this study, three oxicam-bearing non-steroidal anti-inflammatroy drugs(NSAIDs), such as meloxicam, piroxicam and tenoxicam, were identified to have novel neuroprotective mechanism of maintaining phosphatidylinositol 3-kinase(PI3K)/Akt signaling against MPP^+-induced toxicity using neuroblastoma SH-SY5Y cells. The other types of NSAIDs did not show neuroprotection in the same assays. In a chronic mouse model of Parkinson's disease, meloxicam ameliorated motor dysfunction and dopaminergic neurodegeneration by maintaining Akt-signaling. These results suggest that meloxicam would be a candidate agent as a disease-modifying drug for Parkinson's disease.