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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
 
 

Entacapone, a novel catechol-O-methyltransferase inhibitor for Parkinson's disease, does not impair mitochondrial energy production.

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.[1]

References

  1. Entacapone, a novel catechol-O-methyltransferase inhibitor for Parkinson's disease, does not impair mitochondrial energy production. Nissinen, E., Kaheinen, P., Penttilä, K.E., Kaivola, J., Lindén, I.B. Eur. J. Pharmacol. (1997) [Pubmed]
 
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