Catechol-O-methyltransferase and its inhibitors in Parkinson's disease.
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Bonifacio MJ, Palma PN, Almeida L, Soares-da-Silva P
Catechol-O-methyltransferase and its inhibitors in Parkinson's disease.
CNS Drug Rev. 2007 Fall;13(3):352-79. doi: 10.1111/j.1527-3458.2007.00020.x.
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- 17894650 [ View in PubMed]
- Abstract
Parkinson's disease (PD) is a neurological disorder characterized by the degeneration of dopaminergic neurons, with consequent reduction in striatal dopamine levels leading to characteristic motor symptoms. The most effective treatment for this disease continues to be the dopamine replacement therapy with levodopa together with an inhibitor of aromatic amino acid decarboxylase (AADC). The efficacy of this therapy, however, decreases with time and most patients develop fluctuating responses and dyskinesias. The last decade showed that the use of catechol-O-methyltransferase inhibitors as adjuvants to the levodopa/AADC inhibitor therapy, significantly improves the clinical benefits of this therapy. The purpose of this article is to review the current knowledge on the enzyme catechol-O-methyltransferase (COMT) and the role of COMT inhibitors in PD as a new therapeutic approach to PD involving conversion of levodopa to dopamine at the target region in the brain and facilitation of the continuous action of this amine at the receptor sites. A historical overview of the discovery and development of COMT inhibitors is presented with a special emphasis on nebicapone, presently under clinical development, as well as entacapone and tolcapone, which are already approved as adjuncts in the therapy of PD. This article reviews human pharmacokinetic and pharmacodynamic properties of these drugs as well as their clinical efficacy and safety.
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interactions in your softwareApomorphineTestosterone propionate The metabolism of Apomorphine can be decreased when combined with Testosterone propionate. Apomorphine3,5-Dinitrocatechol The metabolism of Apomorphine can be decreased when combined with 3,5-Dinitrocatechol. Conjugated estrogensEntacapone The metabolism of Conjugated estrogens can be decreased when combined with Entacapone. Conjugated estrogens3,5-Dinitrocatechol The metabolism of Conjugated estrogens can be decreased when combined with 3,5-Dinitrocatechol. Conjugated estrogensTolcapone The metabolism of Conjugated estrogens can be decreased when combined with Tolcapone.