Nonsteroidal anti-inflammatory drugs in Parkinson's disease: possible involvement of quinone formation.
It has been revealed that nonsteroidal anti-inflammatory drugs (NSAIDs) have neuroprotective properties based not only on their cyclooxygenase-inhibitory action, but also on other properties including their inhibitory effects on the synthesis of nitric oxide radicals and agonistic action for peroxisome proliferator-activated receptor gamma, in addition to some as yet unknown properties. Recently, a number of experimental and clinical studies have examined the neuroprotective effects of NSAIDs on the pathogenesis of several neurodegenerative diseases, including Parkinson's disease. In this article, various pharmacological effects of NSAIDs (except for their cyclooxygenase-inhibitory action) are reviewed, and possible neuroprotective effects of NSAIDs on Parkinson's disease are discussed. The neurotoxicity of dopamine quinones, or DOPA quinones, has recently received attention as a dopaminergic neuron-specific oxidative stress that is known to play a role in the pathogenesis of Parkinson's disease and neurotoxin-induced parkinsonism. NSAIDs inhibit prostaglandin H synthase, thus suppressing dopamine oxidation and subsequent dopamine quinone formation. Therefore, this article also reviews possible suppressive effects of some NSAIDs against dopamine quinone generation.
Asanuma
Masato
M
Department of Brain Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, 2-5-1 Shikatacho, Okayama 700-8558, Japan. asachan@cc.okayama-u.ac.jp
Miyazaki
Ikuko
I
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage* / Q000493:pharmacokinetics; D000978:Antiparkinson Agents / Q000008:administration & dosage / Q000493:pharmacokinetics; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D008959:Models, Neurological; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D010300:Parkinson Disease / Q000188:drug therapy* / Q000378:metabolism*; D011809:Quinones / Q000378:metabolism*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000978:Antiparkinson Agents; D011809:Quinones