1. Entacapone, a catechol-O-methyltransferase inhibitor, improves the motor activity and dopamine content of basal ganglia in a rat model of Parkinson's disease induced by Japanese encephalitis virus.
- Author
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Hamaue N, Ogata A, Terado M, Tsuchida S, Yabe I, Sasaki H, Hirafuji M, Togashi H, and Aoki T
- Subjects
- Administration, Oral, Animals, Antiparkinson Agents pharmacology, Antiparkinson Agents therapeutic use, Aromatic Amino Acid Decarboxylase Inhibitors, Basal Ganglia enzymology, Basal Ganglia virology, Catechol O-Methyltransferase metabolism, Catechols therapeutic use, Corpus Striatum drug effects, Corpus Striatum enzymology, Corpus Striatum virology, Dopa Decarboxylase metabolism, Drug Combinations, Drug Synergism, Encephalitis Virus, Japanese physiology, Encephalitis, Japanese complications, Encephalitis, Japanese physiopathology, Enzyme Inhibitors pharmacology, Enzyme Inhibitors therapeutic use, Levodopa administration & dosage, Levodopa adverse effects, Nitriles therapeutic use, Parkinsonian Disorders enzymology, Parkinsonian Disorders virology, Rats, Rats, Inbred F344, Treatment Outcome, Basal Ganglia drug effects, Catechol O-Methyltransferase Inhibitors, Catechols pharmacology, Dopamine metabolism, Nitriles pharmacology, Parkinsonian Disorders drug therapy
- Abstract
Levodopa is the main medication used for the treatment of Parkinson's disease. However, dyskinesia and wearing-off appear after the administration of high-dose levodopa for a long period. To combat the dyskinesia and wearing-off, levodopa is used together with a dopamine (DA) receptor agonist, and the amount of levodopa is decreased. We have reported the monoamine oxidase (MAO)-B inhibitor selegiline to be effective for treating motor dysfunction in Parkinson's disease model rats. We analyzed the improvement in motor functions and catecholamine contents in various brain regions induced by a combination of the catechol-O-methyltransferase (COMT) inhibitor entacapone and a levodopa/dopadecarboxylase inhibitor (DDCI) in Japanese encephalitis virus (JEV) induced Parkinson's disease model rats. Entacapone (10 mg/kg) was administered via a single oral administration with levodopa/DDCI (10 mg/kg). The motor functions of the JEV model rats were significantly worsened, compared with those of the healthy control rats. The motor functions in the Parkinson's disease model rats were significantly recovered to the same levels as the healthy control rats by the combined administration of entacapone and levodopa/DDCI. A significant improvement in motor function was not demonstrated in the case of the administration of levodopa/DDCI alone. The striatal DA concentrations in the model rat brains were significantly increased by using levodopa/DDCI together with entacapone. Motor function was recovered by raising the striatum DA density in the model rats. Thus, COMT inhibitors are useful for decreasing the amount of levodopa administered to Parkinson's disease patients.
- Published
- 2010
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