Phenidone protects the nigral dopaminergic neurons from LPS-induced neurotoxicity

Zhengyi Li, Dong Young Choi, Eun Joo Shin, Randy L. Hunter, Chun Hui Jin, Myung Bok Wie, Min Soo Kim, Seok Joo Park, Guoying Bing, Hyoung Chun Kim

Research output: Contribution to journalArticlepeer-review

25 Scopus citations


Anti-inflammatory drugs such as ibuprofen appear to prevent the development of Parkinson's disease (PD); however, long-term use has undesirable side-effects. A new strategy for anti-inflammatory drug therapy is using a dual inhibitor of COX and lipooxygenase (LOX). Here, we compared the dopaminergic neuroprotective property of phenidone (a dual COX and LOX inhibitor) with COX or LOX inhibitors including SC-560 (a COX-1 inhibitor), aspirin (a COX-1/2 inhibitor), meloxicam (a preferential COX-2 inhibitor), caffeic acid (a 5-LOX inhibitor), and esculetin (a 5, 12-LOX inhibitor) in our lipopolysaccharide (LPS)-induced PD animal model. Our results show that COX-2 and 5-LOX play a major role in LPS-induced dopaminergic neurotoxicity, as meloxicam and phenidone attenuated LPS-induced oxidative stress and meloxicam, phenidone, and caffeic acid attenuated dopaminergic neurodegeneration, while SC-560, aspirin, and esculetin did not. In addition, phenidone was superior in attenuating LPS-induced dopaminergic neurodegeneration and microglia activation, probably as a result of dual inhibition of COX-2 and LOX. Therefore, dual inhibition of COX and LOX with phenidone represents a promising new candidate for anti-inflammatory drug therapy, and may provide a novel therapeutic approach for inflammation-related neurodegenerative diseases including PD.

Original languageEnglish
Pages (from-to)1-6
Number of pages6
JournalNeuroscience Letters
Issue number1
StatePublished - Nov 7 2008


  • Cyclooxygenase
  • Lipooxygenase
  • Lipopolysaccharide
  • Parkinson's disease

ASJC Scopus subject areas

  • Neuroscience (all)


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