Reduced plasma homocysteine levels in levodopa/entacapone treated Parkinson patients

Valkovič, Peter; Benetin, Ján; Blažı́ček, P; Valkovičová, L'udmila; Gmitterová, Karin; Kukumberg, P

doi:10.1016/j.parkreldis.2005.01.007

Cited by 68 publications

(63 citation statements)

References 27 publications

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“…While COMT-inhibitors are used currently in the treatment of PD, recent studies have also discussed the potential use of a COMT-inhibitor such as entacapone to decrease hcy concentrations [9,15,16]. This hypothesis is based on the idea that inhibition of peripheral COMT would not only improve the bioavailability of levodopa due to a decrease in peripheral de gradation, but also lower the hcy levels [9,15].…”

Section: Discussionmentioning

confidence: 99%

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Is There the Preventive Effect of COMT-inhibitor on Parkinson's Disease Associated with Dementia?

Lee

Song

Kim

et al. 2012

Dement Neurocognitive Disord

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Background: Elevated homocysteine (hcy) levels are associated with dementia, which is a frequent nonmotor symptom of Parkinson's disease (PD). High levels of hcy in PD patients treated with levodopa are thought to result from increased synthesis during the metabolism of levodopa by COMT, and that use of a COMT-inhibitor may reduce hcy levels. In this study, we sought to clarify the effects of COMT-inhibitors on dementia in PD patients. Methods: Thirty-eight PD patients without dementia (PDwoD), 35 PD patients with dementia (PDD), and 48 controls were enrolled in this study. All subjects underwent neuropsychological testing and a neurological examination. The hcy levels were measured in all subjects, and the relationship between hcy levels and dementia was evaluated in two PD groups (those that underwent treatment with levodopa-alone versus treatment with levodopa plus a COMT-inhibitor). Results: Patients in the PDD group showed higher hcy levels than patients in the PDwoD group, though there was no significant difference in the hcy level between PDwoD patients and healthy controls. Regarding the effects of a COMT-inhibitor, there was no correlation between hcy levels in the 2 PD subgroups, indicating that there were no significant effects of the COMT-inhibitor on PDD. In addition, the odds ratio for PDD with the use of a COMT-inhibitor was 0.864 (95% CI= 0.342-2.180). Conclusions: These results are in agreement with previous studies in that levodopa treatment in PD patients leads to elevated hcy concentrations. COMT-inhibitors, on the other hand, had no preventive effect on cognitive impairment in PD patients.

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Section: Discussionmentioning

confidence: 99%

“…This hypothesis is based on the idea that inhibition of peripheral COMT would not only improve the bioavailability of levodopa due to a decrease in peripheral de gradation, but also lower the hcy levels [9,15]. Consequently, a lower hcy level could lead to improvement in cognitive impairment in PD patients.…”

Section: Discussionmentioning

confidence: 99%

Is There the Preventive Effect of COMT-inhibitor on Parkinson's Disease Associated with Dementia?

Lee

Song

Kim

et al. 2012

Dement Neurocognitive Disord

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“…32,33 These elevations are blunted when COMT inhibitors are used as adjunctive therapy. 34,35 Studies of the risk of stroke in PD have not consistently demonstrated increased risk. 28 One study showed that the measure of biomarkers for endothelial function in PD patients with modestly elevated HC levels was normal.…”

Section: Safety Issues: Elevated Homocysteinementioning

confidence: 99%

Current Status of Symptomatic Medical Therapy in Parkinson’s Disease

Factor

2008

Neurotherapeutics

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Summary: Symptomatic medical therapies for Parkinson's disease (PD) have been disease modifying and have led to improvement in daily function, quality of life, and survival. For 40 years, these therapies have been primarily dopaminergic, and currently include the dopamine (DA) precursor levodopa (LD), DA agonists, catechol-O-methyltransferase (COMT) inhibitors, and monoamine oxidase (MAO) inhibitors. The roles of all these classes of agents have evolved, with significant changes occurring since the early 2000s. This article reviews the current literature for each of these classes of drugs, with a focus on efficacy and place in the therapeutic scheme. Levodopa is no longer considered to be toxic and, thus, its early use is not only appropriate but recommended.Ergot agonists are no longer in use, and new agents administered in patch form or subcutaneous injections have been approved. The COMT inhibitor tolcapone, with its significant efficacy, has been reintroduced, and two new MAO inhibitors have been approved. Selected safety issues are discussed, including the incidence of melanoma in relation to LD; pathological gambling and DA agonists; hepatic toxicity of tolcapone; and the tyramine or so-called cheese reaction with MAO B inhibitors. The article closes with a discussion of future directions and new drugs under development.

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“…41 The effect of combining COMT inhibitors with L-dopa to avoid HHcy is inconclusive. [42][43][44] The available evidence suggests that folate, vitamin B 6 , and vitamin B 12 , but not COMT inhibitors, are the most important modifiers of the effect of L-dopa on Hcy levels. [45][46][47] It seems that higher concentrations of Hcy in PD patients are generally associated with poor progression of the disease.…”

Section: Homocysteine In Patients With Parkinson's Diseasementioning

confidence: 99%

Evaluation of the Current Evidence on Hyperhomocysteinemia in Neurological Diseases

Obeid¹,

Faßbender²,

Herrmann³

2008

US Neurology

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Homocysteine (Hcy) is the demethylated product of methionine. This toxic amino acid can be removed by remethylation to methionine via methionine synthase, which utilizes 5-methyl tetrahydrofolate as a methyl donor and methyl cobalamin as a co-factor. An alternative remethylation pathway for Hcy depends on betaine-Hcy-methyltransferase, which utilizes betaine as a methyl donor. Another method of Hcy catabolism is via two vitamin-B 6 -dependent enzymes, cystathionine beta synthase and cystathioninase, to cysteine. subjects 70-79 years of age were followed for a mean of seven years. The

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Reduced plasma homocysteine levels in levodopa/entacapone treated Parkinson patients

Cited by 68 publications

References 27 publications

Is There the Preventive Effect of COMT-inhibitor on Parkinson's Disease Associated with Dementia?

Is There the Preventive Effect of COMT-inhibitor on Parkinson's Disease Associated with Dementia?

Current Status of Symptomatic Medical Therapy in Parkinson’s Disease

Evaluation of the Current Evidence on Hyperhomocysteinemia in Neurological Diseases

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