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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
2-3
|
| pubmed:dateCreated |
1998-4-3
|
| pubmed:abstractText |
Entacapone, a novel mainly peripherally acting catechol-O-methyltransferase inhibitor used in the treatment of Parkinson's disease, was evaluated for its possible uncoupling activity in cell culture, in rat liver mitochondria, and in isolated guinea-pig heart. Entacapone did not stimulate respiration in the L1210 murine T cell lymphoma cell line at the concentrations studied (5-40 microM). Furthermore, entacapone neither increased mitochondrial respiration nor impaired cardiac function at pharmacologically relevant concentrations (< 10 microM). In fact, the threshold concentration for increased mitochondrial oxygen consumption was 20 microM and half-maximal stimulation of respiration was not detected until 58 microM. Surprisingly, tolcapone, another catechol-O-methyltransferase inhibitor, which acts both peripherally and centrally, stimulated respiration in L1210 cells at the lowest concentration studied (5 microM). In addition, 1 microM tolcapone increased mitochondrial respiration, indicating that it caused uncoupling at a much lower concentration than that of 2,4-dinitrophenol, a well-known uncoupler of oxidative phosphorylation. Tolcapone also impaired the mechanical function and oxygen consumption of the isolated guinea-pig heart at 1 microM. These results show that peripherally acting entacapone, unlike the brain-penetrating tolcapone, is a safe catechol-O-methyltransferase inhibitor for the treatment of Parkinson's disease, since it does not interfere with mitochondrial energy metabolism at pharmacologically effective concentrations.
|
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Adenine Nucleotides,
http://linkedlifedata.com/resource/pubmed/chemical/Antiparkinson Agents,
http://linkedlifedata.com/resource/pubmed/chemical/Catechol O-Methyltransferase,
http://linkedlifedata.com/resource/pubmed/chemical/Catechols,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Nitriles,
http://linkedlifedata.com/resource/pubmed/chemical/entacapone
|
| pubmed:status |
MEDLINE
|
| pubmed:month |
Dec
|
| pubmed:issn |
0014-2999
|
| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:day |
11
|
| pubmed:volume |
340
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
287-94
|
| pubmed:dateRevised |
2007-11-15
|
| pubmed:meshHeading |
pubmed-meshheading:9537825-Adenine Nucleotides,
pubmed-meshheading:9537825-Animals,
pubmed-meshheading:9537825-Antiparkinson Agents,
pubmed-meshheading:9537825-Catechol O-Methyltransferase,
pubmed-meshheading:9537825-Catechols,
pubmed-meshheading:9537825-Cell Respiration,
pubmed-meshheading:9537825-Energy Metabolism,
pubmed-meshheading:9537825-Enzyme Inhibitors,
pubmed-meshheading:9537825-Female,
pubmed-meshheading:9537825-Guinea Pigs,
pubmed-meshheading:9537825-Heart,
pubmed-meshheading:9537825-Kinetics,
pubmed-meshheading:9537825-Leukemia L1210,
pubmed-meshheading:9537825-Male,
pubmed-meshheading:9537825-Mice,
pubmed-meshheading:9537825-Mitochondria, Liver,
pubmed-meshheading:9537825-Nitriles,
pubmed-meshheading:9537825-Oxidative Phosphorylation,
pubmed-meshheading:9537825-Oxygen Consumption,
pubmed-meshheading:9537825-Rats,
pubmed-meshheading:9537825-Rats, Wistar
|
| pubmed:year |
1997
|
| pubmed:articleTitle |
Entacapone, a novel catechol-O-methyltransferase inhibitor for Parkinson's disease, does not impair mitochondrial energy production.
|
| pubmed:affiliation |
Orion Pharma Research, Pharmacolocigal and Toxicological Research, Espoo, Finland. erkki.nissinen@orion.mailnet.fi
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| pubmed:publicationType |
Journal Article,
In Vitro
|