Acute homocysteine rise after repeated levodopa application in patients with Parkinson’s disease

Müller, Thomas; Muhlack, Siegfried

doi:10.1016/j.parkreldis.2010.07.012

Cited by 17 publications

(14 citation statements)

References 5 publications

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“…The present pharmacokinetic study, that EN at least prevents a further homocysteine rise in association with an increased plasma occurrence of levodopa as a result of peripheral COMT inhibition (Valkovic et al 2005;Lamberti et al 2005;Muller and Muhlack 2009;Nevrly et al 2010). But this trial also shows a general tendency of homocysteine accumulation during repeated acute oral levodopa/DDI administration with and without EN over the threshold of 15 μmol/l within 2 days (Muller and Muhlack 2010). Expectedly, there was a general increase of levodopa plasma occurrence with additional EN application (Kuoppamaki et al 2009).…”

Section: Discussionmentioning

confidence: 42%

Inhibition of catechol-O-methyltransferase modifies acute homocysteine rise during repeated levodopa application in patients with Parkinson’s disease

Müller

Woitalla

Muhlack

2011

Naunyn-Schmiedeberg's Arch Pharmacol

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Elevation of plasma total homocysteine concentrations were observed in levodopa/dopa decarboxylase inhibitor (DDI)-treated patients with Parkinson's disease (PD). Degradation of levodopa to 3-O-methyldopa via the enzyme catechol-O-methyltransferase (COMT) is a methyl group demanding reaction. It generates homocysteine from the methyl group donor methionine. But there are inconsistent outcomes, as most investigators determined homocysteine after an overnight washout of levodopa. They did not consider the acute effects of levodopa/DDI intake in relation with COMT inhibition on homocysteine bioavailability. The purpose of this study is to measure levels of homocysteine, levodopa, and its metabolite 3-O-methyldopa in plasma after reiterated oral levodopa/DDI administration with and without the COMT-inhibitor entacapone (EN). Sixteen PD patients received 100 mg levodopa/carbidopa three times on day 1 and with EN on day 2 under standardized conditions. Homocysteine concentrations increased on day 1 and generally over the whole interval. No significant ascent of homocysteine appeared on day 2 only. Levodopa bioavailability was higher on day 2 due to the COMT inhibition. No change of 3-O-methyldopa appeared between both days. The correlation coefficients between homocysteine, levodopa, and 3-O-methyldopa were higher on day 1 than on day 2. Rise of homocysteine does not only depend on the oral levodopa dose, but also on the acute intake of levodopa/DDI with or without COMT inhibition. Measurements of homocysteine should consider acute repeated levodopa/DDI applications, as homocysteine and metabolically related 3-O-methyldopa accumulate due to their long plasma half-life in contrast to short-living levodopa.

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Section: Discussionmentioning

confidence: 42%

Inhibition of catechol-O-methyltransferase modifies acute homocysteine rise during repeated levodopa application in patients with Parkinson’s disease

Müller

Woitalla

Muhlack

2011

Naunyn-Schmiedeberg's Arch Pharmacol

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“…In fact, levodopa is usedat least temporarily-in the treatment of many patients with PSP. According to recent reports levodopa may cause polyneuropathy in patients with Parkinson's disease by increasing homocysteine level [9,10].…”

Section: Introductionmentioning

confidence: 99%

Electrophysiological features of lower motor neuron involvement in progressive supranuclear palsy

Gaweł

Jamrozik

Szmidt-Salkowska

et al. 2013

Journal of the Neurological Sciences

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“…Recent reports indicate that levodopa may cause polyneuropathy in patients with Parkinson's disease by increasing homocysteine level [16][17][18][19]. A similar mechanism of neuropathy has not been considered in MSA.…”

Section: Introductionmentioning

confidence: 99%

Is peripheral neuron degeneration involved in multiple system atrophy? A clinical and electrophysiological study

Gaweł

Jamrozik

Szmidt-Salkowska

et al. 2012

Journal of the Neurological Sciences

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Acute homocysteine rise after repeated levodopa application in patients with Parkinson’s disease

Cited by 17 publications

References 5 publications

Inhibition of catechol-O-methyltransferase modifies acute homocysteine rise during repeated levodopa application in patients with Parkinson’s disease

Inhibition of catechol-O-methyltransferase modifies acute homocysteine rise during repeated levodopa application in patients with Parkinson’s disease

Electrophysiological features of lower motor neuron involvement in progressive supranuclear palsy

Is peripheral neuron degeneration involved in multiple system atrophy? A clinical and electrophysiological study

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