The central catechol-O-methyltransferase inhibitor tolcapone increases striatal hydroxyl radical production in L-DOPA/carbidopa treated rats

Journal of Neural Transmission
M GerlachP Riederer

Abstract

Inhibition of catechol catechol-O-methyltransferase (COMT) in the brains of subjects treated with L-DOPA (L-3,4-dihydroxylphenylalanine) and an aromatic amino acid decarboxylase (AADC) inhibitor is suggested to cause an increase of L-DOPA, which might lead to oxidative damage through enhanced formation of free radicals. To investigate this hypothesis, the acute effects of two doses of the systemically administered COMT inhibitors entacapone (peripheral) and tolcapone (peripheral and central) on the extracellular formation of hydroxyl radicals in vivo following treatment with L-DOPA and the AADC inhibitor carbidopa were examined. The formation of extracellular hydroxyl radicals were determined by the measurement of 2,3-dihydroxybenzoic acid (2,3-DHBA), a reaction product of hydroxyl radicals with sodium salicylate, using microdialysis in the striatum of anesthetised rats. The COMT inhibitors were administered together with 50 mg/kg i.p. carbidopa as 5% gum arabic suspensions intraperitoneally (i.p.) at doses of 0, 1.0, and 10 mg/kg body weight to a total of 36 male HAN-Wistars rats. L-DOPA was injected i.p. 40 min after drugs of interest. Microdialysis samples were collected every 20 min for 400 min at a perfusion rate of 1 micr...Continue Reading

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Citations

Sep 21, 2004·Naunyn-Schmiedeberg's Archives of Pharmacology·Markus M ForsbergPekka T Männistö
Apr 15, 2004·Neurochemistry International·Alvaro Hermida-AmeijeirasRamón Soto-Otero
Dec 24, 2009·Cardiovascular Psychiatry and Neurology·Thomas Müller
Oct 27, 2004·Naunyn-Schmiedeberg's Archives of Pharmacology·Manfred GerlachPeter Riederer
Oct 22, 2002·Expert Opinion on Pharmacotherapy·Thomas Müller
May 12, 2009·Biochemical Pharmacology·Jofre Tenorio-LarangaJ Arturo García-Horsman
Jun 27, 2020·Fortschritte der Neurologie-Psychiatrie·Dirk WoitallaUllrich Wüllner

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