The COX-2 inhibitor parecoxib produces neuroprotective effects in MPTP-lesioned rats

Reksidler, Angela B.; Lima, Marcelo M.S.; Zanata, Sı́lvio M.; Machado, Hidevaldo B.; Cunha, Cláudio Da; Andreatini, Roberto; Tufik, Sérgio; Vital, Maria A.B.F.

doi:10.1016/j.ejphar.2006.12.032

Cited by 65 publications

(33 citation statements)

References 64 publications

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“…Moreover, the selective inhibition of COX-2 prevented microglial activation and loss of nigral dopaminergic neurons induced by MPTP and 6-OHDA. This data suggests therapeutic efficacy of COX-2 inhibitors against the neurodegeneration 28,30 . Some NSAIDs also have antioxidant properties due to their ability to scavenge free radicals and/or to reduce their production.…”

Section: Therapeutic Evidence Of Anti-inflammatory Drugs In Parkinsonmentioning

confidence: 91%

Neuroinflammation in the pathophysiology of Parkinson’s disease and therapeutic evidence of anti-inflammatory drugs

Bassani

Vital

Rauh

2015

Arq. Neuro-Psiquiatr.

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Parkinson's disease (PD) is the second most common neurodegenerative disease affecting 1.6% of people over 60 years old 1,2 . PD is also the most common cause of parkinsonism, corresponding to 74.7% of all cases in a Brazilian study 3 . The disease is characterized by the progressive degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNpc), loss of their ascending projections to the striatum (caudate and putamen), and consequent decrease of striatal dopamine (DA) content, which leads to severe locomotion difficulties and cardinal motor symptoms such as tremor at rest, rigidity, postural instability and slowness of body movements (bradykinesia) 4,5 . By the time a patient is diagnosed, approximately 60% of SNpc neurons are degenerated and 80% of striatal DA content is depleted 4,5 . In addition to neuronal damage, PD is characterized by the presence of proteinaceous inclusions called Lewy bodies and Lewy neurites, mainly in the SNpc 6 . Currently, the pharmacological and non-pharmacological treatments approved for PD offer only symptomatic relief for patients. As these treatments are not able to stop or reverse the neurodegenerative process, PD remains incurable. The motor symptoms can be reduced by many drugs that increase the DA level in the central nervous system (CNS) or mimic its effects. The gold standard for the treatment of PD nowadays is Levodopa, a DA precursor. Other drugs commonly prescribed are DA receptor agonists, monoaminoxidase (MAO) AbStrACtParkinson's disease (PD) is the second most common neurodegenerative disease affecting approximately 1.6% of the population over 60 years old. The cardinal motor symptoms are the result of progressive degeneration of substantia nigra pars compacta dopaminergic neurons which are involved in the fine motor control. Currently, there is no cure for this pathology and the cause of the neurodegeneration remains unknown. Several studies suggest the involvement of neuroinflammation in the pathophysiology of PD as well as a protective effect of anti-inflammatory drugs both in animal models and epidemiological studies, although there are controversial reports. In this review, we address evidences of involvement of inflammatory process and possible therapeutic usefulness of anti-inflammatory drugs in PD.Keywords: Parkinson's disease, neuroinflammation, anti-inflammatory. ResumoA doença de Parkinson (DP) é a segunda doença neurodegenerativa mais comum afetando aproximadamente 1,6% da população acima de 60 anos de idade. Os sinais motores cardinais são o resultado da degeneração progressiva de neurônios dopaminérgicos da substantia nigra pars compacta (SNpc), a qual está intimamente envolvida com o controle motor. Atualmente, não há cura para esta patologia e a causa da neurodegeneração permanece desconhecida. Contudo, muitos estudos sugerem o envolvimento da neuroinflamação na patofisiologia da DP bem como um efeito protetor de drogas antiinflamatórias tanto em modelos animais quanto em estudos epidemiológicos, embora haja relatos controversos. ...

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Section: Therapeutic Evidence Of Anti-inflammatory Drugs In Parkinsonmentioning

confidence: 91%

Neuroinflammation in the pathophysiology of Parkinson’s disease and therapeutic evidence of anti-inflammatory drugs

Bassani

Vital

Rauh

2015

Arq. Neuro-Psiquiatr.

Self Cite

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“…The selective COX-2 inhibitor rofecoxib exhibited a neuroprotective effect. Other studies have also shown that the selective COX-2 inhibitor paracoxib exhibits neuroprotective activity in animal models of PD (74,75).…”

Section: Cox and The Central Nervous System (Cns)mentioning

confidence: 99%

Evolution of Nonsteroidal Anti-Inflammatory Drugs (NSAIDs): Cyclooxygenase (COX) Inhibition and Beyond

Rao

Knaus²

2008

J Pharm Pharm Sci

597

391

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ABSTRACT. Purpose. NSAIDs constitute an important class of drugs with therapeutic applications that have spanned several centuries. Treatment of inflammatory conditions such as rheumatoid arthritis (RA) and osteoarthritis (OA) starting from the classic drug aspirin to the recent rise and fall of selective COX-2 inhibitors has provided an enthralling evolution. Efforts to discover an ultimate magic bullet to treat inflammation continues to be an important drug design challenge. This review traces the origins of NSAIDs, their mechanism of action at the molecular level such as cyclooxygenase (COX) inhibition, development of selective COX-2 inhibitors, their adverse cardiovascular effects, and some recent developments targeted to the design of effective anti-inflammatory agents with reduced side effects. Methods. Literature data is presented describing important discoveries pertaining to the sequential development of classical NSAIDs and then selective COX-2 inhibitors, their mechanism of action, the structural basis for COX inhibition, and recent discoveries. Results. A brief history of the development of NSAIDs and the market withdrawal of selective COX-2 inhibitors is explained, followed by the description of prostaglandin biosynthesis, COX isoforms, structure and function. The structural basis for COX-1 and COX-2 inhibition is described along with methods used to evaluate COX-1/COX-2 inhibition. This is followed by a section that encompasses the major chemical classes of selective COX-2 inhibitors. The final section describes briefly some of the recent advances toward developing effective anti-inflammatory agents such as nitric oxide donor NO-NSAIDs, dual COX/LOX inhibitors and anti-TNF therapy. Conclusions. A great deal of progress has been made toward developing novel anti-inflammatory agents. In spite of the tremendous advances in the last decade, the design and development of a safe, effective and economical therapy for treating inflammatory conditions still presents a major challenge.

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“…On the other hand, numerous findings have instead emphasized the selective involvement of COX-2 inhibition in NSAIDs neuroprotective effects [107,111]. Pre-treatment with COX-2 inhibitors has constantly induced neuroprotection [111,112], supporting a possible role for them as prophylactic therapy for PD.…”

Section: Aspirin In Pd Prevention?mentioning

confidence: 99%

“…Pre-treatment with COX-2 inhibitors has constantly induced neuroprotection [111,112], supporting a possible role for them as prophylactic therapy for PD. Nevertheless, the selective COX-2 inhibitor indomethacin, did not show any neuroprotective effect when administered after toxin-induced nigral degeneration, revealing that the time of COX-2 inhibition is critical to achieve a protective effect [113].…”

Section: Aspirin In Pd Prevention?mentioning

confidence: 99%

Will it Ever Become Possible to Prevent Dopaminergic Neuronal Degeneration?

Giovanni

2008

CNSNDDT

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Abstract:Parkinson's disease (PD) is the second leading age-related degenerative brain disease in the world affecting millions of people. This neurological disorder disrupts the quality of life of patients and their families, exerts an enormous emotional and physical strain on caregivers, and has a large cost for society. Moreover, the increasing numbers of elderly people in the population will result in a sharp increase in the prevalence of PD. The understanding of its pathophysiology and treatment has advanced at a very impressive rate during past decades. Nevertheless, PD is still fatal and there is at present no cure for it. Furthermore, there are no proven therapies for prevention of PD and although evidence exists of risk and protective factors, this is not strong enough to warrant specific measures in an attempt to diminish risk or enhance protection. Drug development programmes are engaged in finding neuroprotective and neurorestorative therapies or, even better, discovering drugs able to rejuvenate the dopaminergic neurons. The latest developments in this promising field will be discussed with reference to the current literature together with the advantages and pitfalls of suggested drugs. Finally, an analysis of the role of various dietary recommendations, lifestyle, environmental and other factors in reducing the risk of PD is carried out.

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The COX-2 inhibitor parecoxib produces neuroprotective effects in MPTP-lesioned rats

Cited by 65 publications

References 64 publications

Neuroinflammation in the pathophysiology of Parkinson’s disease and therapeutic evidence of anti-inflammatory drugs

Neuroinflammation in the pathophysiology of Parkinson’s disease and therapeutic evidence of anti-inflammatory drugs

Evolution of Nonsteroidal Anti-Inflammatory Drugs (NSAIDs): Cyclooxygenase (COX) Inhibition and Beyond

Will it Ever Become Possible to Prevent Dopaminergic Neuronal Degeneration?

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