当前位置： SCI文献检索 > CLINICAL NEUROPHARMACOLOGY期刊下所有文献 > Catechol-O-methyltransferase inhibition improves levodopa-associated strength increase in patients with Parkinson disease.

Catechol-O-methyltransferase inhibition improves levodopa-associated strength increase in patients with Parkinson disease.

Abstract：

:A matter of debate is the impact of levodopa (LD) application in patients with Parkinson disease (PD) on altered force development and coordination, which are also influenced by the strength of muscles used. The objectives were to compare the motor response, the development of grip strength, and the pharmacokinetic behavior of LD and its main peripheral metabolite 3-O-methyldopa (3-OMD) after intake of 200-mg retarded-release levodopa/carbidopa (LD/CD) and of 150-mg LD/CD/entacapone (LD/CD/EN). Twelve patients with PD received both LD formulations within a standardized setting under double-blind conditions with a crossover design 1 day after the other. Motor symptoms significantly improved, LD plasma concentrations went up, and grip strength increased after both LD/CD and LD/CD/EN administration. There were no significant differences between both conditions with regard to motor response and LD pharmacokinetics. The 3-OMD levels were significantly lower during catechol-O-methyltransferase (COMT) inhibition with entacapone. The LD/CD/EN compound was superior over the retarded-release LD formulation, indicating the impact of LD on grip force. This may be caused by the interference of 3-OMD with the blood-brain barrier transport of LD; therefore, LD delivery is greater during the LD/CD/EN condition. Because the rating scale used does not consider the grip strength, this effect of better blood barrier transport of LD was not reflected. Another hypothesis may be that more acidic metabolites appear during peripheral LD metabolism by means of COMT, whereas COMT inhibition is accompanied by more basic LD metabolites (ie, the tyrosine aminotransferase-dependent substrates dihydroxyphenylpyruvate acetate and trihydroxyphenylacetate). This antiacid scenario may support a better muscle function with a positive impact on muscle excitability and contractibility.

journal_name

Clin Neuropharmacol

journal_title

Clinical neuropharmacology

authors

Müller T,Kolf K,Ander L,Woitalla D,Muhlack S

doi

10.1097/WNF.0b013e31811510ed

subject

Has Abstract

pub_date

2008-05-01 00:00:00

pages

134-40

issue

eissn

0362-5664

issn

1537-162X

pii

00002826-200805000-00002

journal_volume

pub_type

杂志文章

在线工具

Catechol-O-methyltransferase inhibition improves levodopa-associated strength increase in patients with Parkinson disease.