PMID: 9537825: Entacapone does not impair mitochondrial energy production.

[janet paterson <janet313@xxxxxxxxxxx>]

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.


Eur J Pharmacol 1997 Dec 11;340(2-3):287-94
Nissinen E, Kaheinen P, Penttila KE, Kaivola J, Linden IB
Orion Pharma Research, Espoo, Finland.
<erkki.nissinen@xxxxxxxxxxxxxxxx>
PMID: 9537825, UI: 98141050

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janet paterson
52 now / 41 dx / 37 onset
613 256 8340 po box 171 almonte ontario canada K0A 1A0
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<janet313@xxxxxxxxxxx>