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.

Ongentys (Opicapone): A New COMT Inhibitor for the Treatment of Parkinson’s Disease

2020 ◽  
pp. 106002802097456
Author(s):  
Erin St. Onge ◽  
Michelle Vanderhoof ◽  
Shannon Miller
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Data Extraction ◽  
Adjunctive Treatment ◽  
Comt Inhibition ◽  
Comt Inhibitors ◽  
Once Daily ◽  
Safety And Efficacy ◽  
Comt Inhibitor ◽  
Preclinical Trials

Objective To describe the safety and efficacy of opicapone, a newly Food and Drug Administration–approved catechol- O-methyltransferase (COMT) inhibitor, as an adjunctive treatment to levodopa/carbidopa in patients with Parkinson’s disease (PD) experiencing off episodes. Data Sources A literature search through PubMed and International Pharmaceutical Abstracts (January 2000 to October 2020) was conducted using the following search terms: Ongentys, opicapone, COMT inhibitor, Parkinson’s disease, and Parkinson’s. Study Selection and Data Extraction Articles selected included those describing preclinical and clinical studies examining the pharmacokinetics, efficacy, and/or safety of opicapone. Data Synthesis In preclinical trials, opicapone demonstrated marked S-COMT inhibition, despite its short half-life, while maintaining an acceptable safety and efficacy profile. Results from phase 3 clinical trials further supported the safety and efficacy of opicapone as an adjunct to levodopa. In addition, opicapone, at a dose of 50 mg once daily, was shown to be superior to placebo and noninferior to entacapone in reducing time spent in the off state. Adverse effects commonly reported with opicapone include dyskinesias, constipation, hypotension/syncope, increased blood creatine kinase, and decreased weight. Relevance to Patient Care and Clinical Practice Additional medications, such as COMT inhibitors, become necessary adjunctive treatments as the disease progresses. Compared to other COMT inhibitors currently on the US market, opicapone offers the advantage of once-daily dosing. Conclusion Opicapone is a safe and effective COMT inhibitor shown to reduce off episodes in patients with PD.

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 Iron Dysregulation and Inflammagens Related to Oral and Gut Health Are Central to the Development of Parkinson’s Disease

Biomolecules ◽  
2020 ◽  
Vol 11 (1) ◽  
pp. 30
Author(s):  
Marthinus Janse van Vuuren ◽  
Theodore Albertus Nell ◽  
Jonathan Ambrose Carr ◽  
Douglas B. Kell ◽  
Etheresia Pretorius
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Systemic Inflammation ◽  
Cell Damage ◽  
Vascular Dysfunction ◽  
Iron Chelation ◽  
Gut Health ◽  
Novel Treatments ◽  
Randomized Controlled Clinical Trials ◽  
Iron Dysregulation

Neuronal lesions in Parkinson’s disease (PD) are commonly associated with α-synuclein (α-Syn)-induced cell damage that are present both in the central and peripheral nervous systems of patients, with the enteric nervous system also being especially vulnerable. Here, we bring together evidence that the development and presence of PD depends on specific sets of interlinking factors that include neuroinflammation, systemic inflammation, α-Syn-induced cell damage, vascular dysfunction, iron dysregulation, and gut and periodontal dysbiosis. We argue that there is significant evidence that bacterial inflammagens fuel this systemic inflammation, and might be central to the development of PD. We also discuss the processes whereby bacterial inflammagens may be involved in causing nucleation of proteins, including of α-Syn. Lastly, we review evidence that iron chelation, pre-and probiotics, as well as antibiotics and faecal transplant treatment might be valuable treatments in PD. A most important consideration, however, is that these therapeutic options need to be validated and tested in randomized controlled clinical trials. However, targeting underlying mechanisms of PD, including gut dysbiosis and iron toxicity, have potentially opened up possibilities of a wide variety of novel treatments, which may relieve the characteristic motor and nonmotor deficits of PD, and may even slow the progression and/or accompanying gut-related conditions of the disease.

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

scholarly journals The Efficacy of Iron Chelators for Removing Iron from Specific Brain Regions and the Pituitary—Ironing out the Brain

2019 ◽  
Vol 12 (3) ◽  
pp. 138 ◽  
Author(s):  
Robert R. Crichton ◽  
Roberta J. Ward ◽  
Robert C. Hider
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Iron Chelation ◽  
Brain Regions ◽  
Beta Thalassemia ◽  
Excess Iron ◽  
New Class ◽  
Clinical Conditions ◽  
The Brain

Iron chelation therapy, either subcutaneous or orally administered, has been used successfully in various clinical conditions. The removal of excess iron from various tissues, e.g., the liver spleen, heart, and the pituitary, in beta thalassemia patients, has become an essential therapy to prolong life. More recently, the use of deferiprone to chelate iron from various brain regions in Parkinson’s Disease and Friederich’s Ataxia has yielded encouraging results, although the side effects, in <2% of Parkinson’s Disease(PD) patients, have limited its long-term use. A new class of hydroxpyridinones has recently been synthesised, which showed no adverse effects in preliminary trials. A vital question remaining is whether inflammation may influence chelation efficacy, with a recent study suggesting that high levels of inflammation may diminish the ability of the chelator to bind the excess iron.

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.

18F-dopa PET evidence that tolcapone acts as a central COMT inhibitor in Parkinson's disease

Synapse ◽  
2002 ◽  
Vol 43 (3) ◽  
pp. 201-207 ◽  
Author(s):  
Roberto Ceravolo ◽  
Paola Piccini ◽  
Dale L. Bailey ◽  
Karin M. Jorga ◽  
Helen Bryson ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Comt Inhibitor
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