RGD Reference Report - Coadministration of entacapone with levodopa attenuates the severity of dyskinesias in hemiparkinsonian rats. - Rat Genome Database

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Coadministration of entacapone with levodopa attenuates the severity of dyskinesias in hemiparkinsonian rats.

Authors: Marin, C  Aguilar, E  Obeso, JA 
Citation: Marin C, etal., Mov Disord. 2006 May;21(5):646-53.
RGD ID: 2289781
Pubmed: PMID:16437585   (View Abstract at PubMed)
DOI: DOI:10.1002/mds.20780   (Journal Full-text)

Levodopa-induced dyskinesias (LIDs) have been associated with a sequence of events that includes pulsatile stimulation of dopamine receptors. The degree of nigrostriatal degeneration, the half-life of dopaminomimetic agents, and the dose of levodopa used to treat parkinsonian symptoms are factors directly correlated with the development of motor complications in Parkinson's disease patients. Long-acting agents producing continuous dopaminergic stimulation are less likely to prime for dyskinesia than short-acting drugs that produce pulsatile stimulation of dopamine receptors. Inhibition of the enzyme catechol-O-methyl transferase (COMT) by entacapone extends the half-life of levodopa and minimizes variability in plasma levodopa levels. The aim of the present study was to characterize the effect of the early administration of the COMT inhibitor entacapone in the recently described model of LIDs in rats with a nigrostriatal lesion induced by 6-hydroxydopamine (6-OHDA). Male Sprague-Dawley rats received a unilateral 6-OHDA administration in the nigrostriatal pathway. Animals were treated either with levodopa (6 mg/kg, twice at day, i.p.) plus entacapone (30 mg/kg per day, i.p.) or levodopa (6 mg/kg, twice at day, i.p.) plus vehicle for 22 consecutive days. Early administration of entacapone, in association with levodopa, induces a decrease in the severity of dyskinesia and delays their onset in hemiparkinsonian rats. All dyskinesia subtypes evaluated, such as axial, limb, and orofacial dyskinesias, have shown similar reductions. These results suggest that entacapone, by extending levodopa elimination half-life, might reduce its propensity to induce motor complications.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Drug-Induced Dyskinesia  ISOComt (Rattus norvegicus)2289781; 2289781 RGD 
Drug-Induced Dyskinesia  IMP 2289781 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Comt  (catechol-O-methyltransferase)

Genes (Mus musculus)
Comt  (catechol-O-methyltransferase)

Genes (Homo sapiens)
COMT  (catechol-O-methyltransferase)


Additional Information