Effects of levodopa and COMT inhibitors on plasma homocysteine in Parkinson's disease patients

2004 ◽  
Vol 20 (1) ◽  
pp. 69-72 ◽  
Author(s):  
Paolo Lamberti ◽  
Stefano Zoccolella ◽  
Giovanni Iliceto ◽  
Elio Armenise ◽  
Angela Fraddosio ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Plasma Homocysteine ◽  
Comt Inhibitors

Management of L-Dopa related hyperhomocysteinemia: catechol-O-methyltransferase (COMT) inhibitors or B vitamins? Results from a review

2007 ◽  
Vol 45 (12) ◽  
Author(s):  
Stefano Zoccolella ◽  
Giovanni Iliceto ◽  
Michele deMari ◽  
Paolo Livrea ◽  
Paolo Lamberti
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Plasma Homocysteine ◽  
B Vitamins ◽  
Elevated Plasma ◽  
Therapeutic Approaches ◽  
Cytotoxic Effects ◽  
Comt Inhibitors ◽  
Clinical Correlations ◽  
Diet Supplementation

AbstractIn recent years, L-Dopa treatment has been indicated as an acquired cause of hyperhomocysteinemia (HHcy). The mechanism underlying L-Dopa-related HHcy is the O-methylation of the drug catalyzed by the enzyme catechol-O-methyltransferase (COMT). Folate and cobalamin status also influences the effects of L-Dopa on plasma homocysteine (Hcy) levels. Although clinical correlations of HHcy in Parkinson's disease still remain uncertain, management of elevated plasma Hcy levels has been advocated, due to multiple cytotoxic effects of Hcy on neurons. This review summarizes data available in the literature concerning the two main therapeutic approaches to L-Dopa-related HHcy (use of COMT inhibitors or B vitamins diet supplementation).Clin Chem Lab Med 2007;45:1607–13.

Impact of oral COMT-inhibitors on gut microbiota and short chain fatty acids in Parkinson's disease

2020 ◽  
Vol 70 ◽  
pp. 20-22 ◽  
Author(s):  
Daniel Grün ◽  
Valerie C. Zimmer ◽  
Jil Kauffmann ◽  
Jörg Spiegel ◽  
Ulrich Dillmann ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Fatty Acids ◽  
Parkinson's Disease ◽  
Gut Microbiota ◽  
Short Chain Fatty Acids ◽  
Short Chain ◽  
Comt Inhibitors ◽  
Chain Fatty Acids

scholarly journals Redefining the strategy for the use of COMT inhibitors in Parkinson’s disease: the role of opicapone

2021 ◽  
pp. 1-15
Author(s):  
Peter Jenner ◽  
José-Francisco Rocha ◽  
Joaquim J Ferreira ◽  
Olivier Rascol ◽  
Patrício Soares-da-Silva
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Comt Inhibitors

Evaluation of Selected Natural Compounds as Dual Inhibitors of Catechol-O-Methyltransferase and Monoamine Oxidase

2019 ◽  
Vol 19 (2) ◽  
pp. 133-145 ◽  
Author(s):  
Idalet Engelbrecht ◽  
Jacobus P. Petzer ◽  
Anél Petzer
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Monoamine Oxidase ◽  
Symptomatic Treatment ◽  
Natural Compounds ◽  
Comt Inhibition ◽  
Comt Inhibitors ◽  
Mao B ◽  
Dual Inhibitors

Background: The most effective symptomatic treatment of Parkinson’s disease remains the metabolic precursor of dopamine, L-dopa. To enhance the efficacy of L-dopa, it is often combined with inhibitors of the enzymes, catechol-O-methyltransferase (COMT) and monoamine oxidase (MAO) B, key metabolic enzymes of L-dopa and dopamine. Objective: This study attempted to discover compounds that exhibit dual inhibition of COMT and MAO-B among a library of 40 structurally diverse natural compounds. Such dual acting inhibitors may be effective as adjuncts to L-dopa and offer enhanced value in the management of Parkinson’s disease. Methods: Selected natural compounds were evaluated as in vitro inhibitors of rat liver COMT and recombinant human MAO. Reversibility of MAO inhibition was investigated by dialysis. Results: Among the natural compounds morin (IC50 = 1.32 µM), chlorogenic acid (IC50 = 6.17 µM), (+)-catechin (IC50 = 0.86 µM), alizarin (IC50 = 0.88 µM), fisetin (IC50 = 5.78 µM) and rutin (IC50 = 25.3 µM) exhibited COMT inhibition. Among these active COMT inhibitors only morin (IC50 = 16.2 µM), alizarin (IC50 = 8.16 µM) and fisetin (IC50 = 7.33 µM) were noteworthy MAO inhibitors, with specificity for MAO-A. Conclusion: None of the natural products investigated here are dual COMT/MAO-B inhibitors. However, good potency COMT inhibitors have been identified, which may serve as leads for future development of COMT inhibitors.

COMT Inhibitors: Novel Treatments for Parkinson's Disease

CNS Spectrums ◽  
1998 ◽  
Vol 3 (2) ◽  
pp. 53-56 ◽  
Author(s):  
Charles H. Adler
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Comt Inhibitors ◽  
Novel Treatments ◽  
New Class ◽  
Comt Inhibitor ◽  
Duration Of Response

AbstractCatechol-O-methyltransferase (COMT) inhibitors are a new class of medication being developed for the treatment of Parkinson's disease (PD). The enzyme COMT metabolizes levodopa and dopamine, both peripherally and centrally. Coadministration of a COMT inhibitor with levodopa creates an increase in peripheral and central levodopa bioavailability, as well as higher central dopamine concentrations. Because these actions improve the duration of response to levodopa, the COMT inhibitors should prove to be useful adjunctive therapies in PD patients.

Plasma homocysteine levels in L-dopa-treated Parkinson's disease patients with cognitive dysfunctions

2005 ◽  
Vol 43 (10) ◽  
Author(s):  
Stefano Zoccolella ◽  
Paolo Lamberti ◽  
Giovanni Iliceto ◽  
Cosimo Diroma ◽  
Elio Armenise ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Plasma Homocysteine ◽  
Vitamin B ◽  
Elevated Plasma ◽  
Cognitive Dysfunctions ◽  
The Relationship ◽  
Late Stages

AbstractElevated plasma homocysteine (Hcy) concentrations are associated with Alzheimer's disease and vascular dementia. Several recent reports have indicated that L-dopa treatment is an acquired cause of hyperhomo-cysteinemia. Despite the fact that a large proportion of Parkinson's disease (PD) patients develop cognitive dysfunctions or dementia, particularly in the late stages of the illness and after long-term L-dopa treatment, the relationship between Hcy and dementia in PD has not been fully investigated. The aim of this study was to evaluate plasma Hcy levels in a group of L-dopa-treated PD patients with cognitive impairment and to elucidate a possible role of Hcy in the development of cognitive dysfunctions in PD. We compared Hcy, vitamin B

The Treatment of Parkinson's Disease in Older People

1997 ◽  
Vol 42 (5) ◽  
pp. 147-150 ◽  
Author(s):  
C.T.C. Lien ◽  
W.J. Mutch
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Older People ◽  
Older Patients ◽  
Dopamine Agonists ◽  
Life Time ◽  
Comt Inhibitors ◽  
Functional Benefit ◽  
Subcutaneous Apomorphine ◽  
Variable Combination

Parkinson's disease is characterised by a variable combination of tremor, rigidity, bradykinesia and impaired righting reflexes. The cumulative life-time risk is one in 40. Levodopa remains the single most effective treatment in older patients, and the minimum dose to achieve maxiumu functional benefit should be employed. When fluctuations occur, controlled release preparations and selegiline can improve function. Oral dopamine agonists have a role but the combined side effect profile with levodopa should be monitored. COMT inhibitors have recently become available. Subcutaneous apomorphine can be helpful when “on-off phenomema are marked. The concept of neuroprotection continues to be debated. Surgery is an option for fitter older people but neurotransplantation remains essentially a research tool.

Parkinson’s Disease: A Review from Pathophysiology to Treatment

2020 ◽  
Vol 20 (9) ◽  
pp. 754-767 ◽  
Author(s):  
Bianca L.B. Marino ◽  
Lucilene R. de Souza ◽  
Kessia P.A. Sousa ◽  
Jaderson V. Ferreira ◽  
Elias C. Padilha ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Elderly Population ◽  
Functional Performance ◽  
Synaptic Cleft ◽  
The Elderly ◽  
Functional Mobility ◽  
Comt Inhibitors ◽  
Mao B ◽  
Physical Limitations

: Parkinson's Disease (PD) is the second most common neurodegenerative disease in the elderly population, with a higher prevalence in men, independent of race and social class; it affects approximately 1.5 to 2.0% of the elderly population over 60 years and 4% for those over 80 years of age. PD is caused by the necrosis of dopaminergic neurons in the substantia nigra, which is the brain region responsible for the synthesis of the neurotransmitter dopamine (DA), resulting in its decrease in the synaptic cleft. The monoamine oxidase B (MAO-B) degrades dopamine, promoting the glutamate accumulation and oxidative stress with the release of free radicals, causing excitotoxicity. The PD symptoms are progressive physical limitations such as rigidity, bradykinesia, tremor, postural instability and disability in functional performance. Considering that there are no laboratory tests, biomarkers or imaging studies to confirm the disease, the diagnosis of PD is made by analyzing the motor features. There is no cure for PD, and the pharmacological treatment consists of a dopaminergic supplement with levodopa, COMT inhibitors, anticholinergics agents, dopaminergic agonists, and inhibitors of MAO-B, which basically aims to control the symptoms, enabling better functional mobility and increasing life expectancy of the treated PD patients. Due to the importance and increasing prevalence of PD in the world, this study reviews information on the pathophysiology, symptomatology as well as the most current and relevant treatments of PD patients.

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