Erythrocytes catechol-o-methyl transferase activity is up-regulated after a 3-month treatment by entacapone in parkinsonian patients
| Autor: | Jean Costentin, Bruno Mihout, Anne Marie Cottard, David Maltête |
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| Rok vydání: | 2010 |
| Předmět: |
Male
medicine.medical_specialty Methyltransferase Erythrocytes Time Factors Catechols Catechol O-Methyltransferase Antiparkinson Agents chemistry.chemical_compound Downregulation and upregulation Internal medicine Nitriles medicine Humans Pharmacology (medical) Entacapone Enzyme Inhibitors Morning Aged Pharmacology Catechol Aromatic L-amino acid decarboxylase business.industry Mean age Parkinson Disease Middle Aged Up-Regulation Endocrinology chemistry Erythrocyte Count Female Neurology (clinical) business Motor disability medicine.drug |
| Zdroj: | Clinical neuropharmacology. 34(1) |
| ISSN: | 1537-162X |
| Popis: | OBJECTIVES Entacapone is a highly potent, reversible, peripherally acting catechol-O-methyl transferase (COMT) inhibitor that is used as an adjunct to L-dopa in the treatment of patients with Parkinson disease (PD). Nevertheless, the consequence of the long-lasting inhibition of COMT by entacapone has never been investigated. We assessed the variation of the soluble red blood cell (S-RBC)-COMT activity after 3 months of chronic treatment by entacapone. METHODS Twelve consecutive white PD patients (3 women and 9 men; mean age, 65.7 ± 2.4 years) with L-dopa-related motor fluctuations were assessed. Entacapone 200 mg was given in combination with each scheduled L-dopa/dopa decarboxylase inhibitor dose (range, 3-5 doses daily). The S-RBC-COMT activity was determined both before entacapone administration (baseline) and twice, respectively, after 1 and 3 months treatment with entacapone, that is, on morning, after at least a 12-hour withdrawal of entacapone and L-dopa and before the following first daily administration. RESULTS Mean baseline S-RBC-COMT activity was 0.72 ± 0.09 pmol/min per milligram (range, 0.30-1.29 pmol/min per milligram) of protein. After 3 months, the level increased significantly in all PD patients from 0.72 ± 0.09 pmol/min per milligram (range, 0.30-1.29 pmol/min per milligram) to 1.19 ± 0.13 pmol/min per milligram (range, 0.58-2.14 pmol/min per milligram) of protein (P < 0.01), which corresponds to a mean increase of 72.9 ± 9.2% (range, 24%-146%). CONCLUSIONS Our findings suggest that a long-lasting inhibition of the COMT may limit the efficacy of entacapone by development of a tolerance. Moreover, one may assume that an abrupt withdrawal of the treatment will be followed by a dramatic worsening of motor disability. |
| Databáze: | OpenAIRE |
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