Nonsteroidal anti-inflammatory drugs in experimental parkinsonian models and Parkinson's disease.
A number of experimental studies using parkinsonian models have revealed that nonsteroidal anti-inflammatory drugs (NSAIDs) have neuroprotective properties against dopaminergic neurotoxicity not only by their cyclooxygenase-inhibiting effect but also by other specific properties or some unknown pharmacological effects. This article reviews heterogeneous pharmacological properties of NSAIDs including inhibitory effect against nitric oxide synthesis, agonistic action for peroxisome proliferator-activated receptor gamma, or possible suppressive effects against dopamine quinone generation, and also reviews their neuroprotective effects in the experimental parkinsonian models and pathogenesis of Parkinson's disease. Several epidemiological studies recently clarified that the use of nonaspirin NSAIDs but not aspirin was associated with a lower prevalence of Parkinson's disease, in contrast with neuroprotective effects of aspirin in the experimental studies. It also discusses the discrepancy between results in the experimental parkinsonian models and epidemiological data in prevalence of Parkinson's disease on the effects of NSAIDs.
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
Masato
M
Asanuma
Ikuko
I
Miyazaki
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology / Q000627:therapeutic use*; D001921:Brain / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D051545:Cyclooxygenase 1 / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D020267:MPTP Poisoning / Q000188:drug therapy / Q000209:etiology / Q000473:pathology; D008959:Models, Neurological; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D047495:PPAR gamma / Q000819:agonists; D010300:Parkinson Disease / Q000188:drug therapy* / Q000453:epidemiology / Q000473:pathology; D010302:Parkinson Disease, Secondary / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D015995:Prevalence
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016861:Cyclooxygenase Inhibitors; D018696:Neuroprotective Agents; D047495:PPAR gamma; D009569:Nitric Oxide; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2