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Tolcapone decreases plasma levels of S-adenosyl-L-homocysteine and homocysteine in treated Parkinson's disease patients.
Eur J Clin Pharmacol. 2006 Jun; 62(6):447-50.EJ

Abstract

BACKGROUND

Elevated plasma total homocysteine (tHcy) appeared in levodopa/dopadecarcoxylase inhibitor (DDI) treated patients with Parkinson's disease (PD). One therapeutic approach for tHcy reduction is vitamine supplementation, since folic acid and cobalamine catalyse and enhance metabolism of tHcy to methionine. A further therapeutic alternative is inhibition of catechol-O-methyltransfrase (COMT) on a regular basis, when levodopa/DDI treatment is performed.

METHODS

We measured the concentrations of S-adenosylmethionine (SAM), S-adenosylhomocysteine (SAH), tHcy, levodopa and 3-O-methyldopa in plasma of 13 levodopa treated PD patients before first drug intake at 0600 hours. Blood samples were taken before and after 2 days of additional application of the centrally acting catechol-O-methyltransferase inhibitor tolcapone 100 mg t.i.d.

RESULTS

Plasma levels of SAH [day 1: 48.32+/-22.52, 23.92-98.25 (mean+/-SD, range; micromol/l); day 3: 37.72+/-15.84, 23.4-61.89; p = 0.01] and tHcy (day 1: 13.88+/-5.62, 7.63-24.81; day 3: 11.38+/-4.44, 5.98-20.45; p = 0.04) significantly reduced. Plasma levels of levodopa did not significantly (p = 0.17) increase, whereas 3-OMD concentrations significantly (p = 0.0002) reduced after additional tolcapone intake. There was no significant change of SAM plasma levels (p = 0.22).

CONCLUSION

Our prospective trial shows, that COMT inhibition with tolcapone lowers tHcy synthesis. Tolcapone may also possess beside its proven, occasional, hepatotoxic potency also beneficial effects via decrease of SAH and tHcy. This may hypothetically reduce homocysteine mediated progress of neuronal degeneration and the risk for onset of dementia, vascular disease and polyneuropathy in levodopa treated PD patients in the long term.

Authors+Show Affiliations

Department of Neurology, St. Josef-Hospital, University of Bochum, Gudrunstr. 56, 44791, Bochum, Germany. thomas.mueller@ruhr-uni-bochum.deNo affiliation info available

Pub Type(s)

Clinical Trial
Journal Article

Language

eng

PubMed ID

16758261

Citation

Müller, Thomas, and Wilfried Kuhn. "Tolcapone Decreases Plasma Levels of S-adenosyl-L-homocysteine and Homocysteine in Treated Parkinson's Disease Patients." European Journal of Clinical Pharmacology, vol. 62, no. 6, 2006, pp. 447-50.
Müller T, Kuhn W. Tolcapone decreases plasma levels of S-adenosyl-L-homocysteine and homocysteine in treated Parkinson's disease patients. Eur J Clin Pharmacol. 2006;62(6):447-50.
Müller, T., & Kuhn, W. (2006). Tolcapone decreases plasma levels of S-adenosyl-L-homocysteine and homocysteine in treated Parkinson's disease patients. European Journal of Clinical Pharmacology, 62(6), 447-50.
Müller T, Kuhn W. Tolcapone Decreases Plasma Levels of S-adenosyl-L-homocysteine and Homocysteine in Treated Parkinson's Disease Patients. Eur J Clin Pharmacol. 2006;62(6):447-50. PubMed PMID: 16758261.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Tolcapone decreases plasma levels of S-adenosyl-L-homocysteine and homocysteine in treated Parkinson's disease patients. AU - Müller,Thomas, AU - Kuhn,Wilfried, Y1 - 2006/04/22/ PY - 2005/12/14/received PY - 2006/03/24/accepted PY - 2006/6/8/pubmed PY - 2007/2/1/medline PY - 2006/6/8/entrez SP - 447 EP - 50 JF - European journal of clinical pharmacology JO - Eur J Clin Pharmacol VL - 62 IS - 6 N2 - BACKGROUND: Elevated plasma total homocysteine (tHcy) appeared in levodopa/dopadecarcoxylase inhibitor (DDI) treated patients with Parkinson's disease (PD). One therapeutic approach for tHcy reduction is vitamine supplementation, since folic acid and cobalamine catalyse and enhance metabolism of tHcy to methionine. A further therapeutic alternative is inhibition of catechol-O-methyltransfrase (COMT) on a regular basis, when levodopa/DDI treatment is performed. METHODS: We measured the concentrations of S-adenosylmethionine (SAM), S-adenosylhomocysteine (SAH), tHcy, levodopa and 3-O-methyldopa in plasma of 13 levodopa treated PD patients before first drug intake at 0600 hours. Blood samples were taken before and after 2 days of additional application of the centrally acting catechol-O-methyltransferase inhibitor tolcapone 100 mg t.i.d. RESULTS: Plasma levels of SAH [day 1: 48.32+/-22.52, 23.92-98.25 (mean+/-SD, range; micromol/l); day 3: 37.72+/-15.84, 23.4-61.89; p = 0.01] and tHcy (day 1: 13.88+/-5.62, 7.63-24.81; day 3: 11.38+/-4.44, 5.98-20.45; p = 0.04) significantly reduced. Plasma levels of levodopa did not significantly (p = 0.17) increase, whereas 3-OMD concentrations significantly (p = 0.0002) reduced after additional tolcapone intake. There was no significant change of SAM plasma levels (p = 0.22). CONCLUSION: Our prospective trial shows, that COMT inhibition with tolcapone lowers tHcy synthesis. Tolcapone may also possess beside its proven, occasional, hepatotoxic potency also beneficial effects via decrease of SAH and tHcy. This may hypothetically reduce homocysteine mediated progress of neuronal degeneration and the risk for onset of dementia, vascular disease and polyneuropathy in levodopa treated PD patients in the long term. SN - 0031-6970 UR - https://www.unboundmedicine.com/medline/citation/16758261/Tolcapone_decreases_plasma_levels_of_S_adenosyl_L_homocysteine_and_homocysteine_in_treated_Parkinson's_disease_patients_ L2 - https://dx.doi.org/10.1007/s00228-006-0132-0 DB - PRIME DP - Unbound Medicine ER -