Catechol-O-methyltransferase inhibitors in the treatment of Parkinson’s disease

Mervat Wahba, Theresa A. Zesiewicz, Robert A. Hauser

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

Parkinson’s disease (PD) is a chronic, neurodegenerative disease associated with a progressive loss of nigrostriatal dopamine neurons and resultant reduced striatal dopamine concentration.1 The cardinal motor features of PD are tremor, bradykinesia, and rigidity. Levodopa, the chemical precursor of dopamine, remains the cornerstone of antiparkinsonian therapy, although its long-term use is hampered by the induction of motor complications including end-of-dose wearing off and dyskinesia.2,3 Although levodopa has a short serum half-life, patients initially experience a sustained clinical response through the day, presumably due to the ability of remaining nigrostriatal neurons to take up levodopa, convert it to dopamine, and then store and release dopamine into the synaptic cleft over time.4,5 As more and more dopamine neurons are lost, this storage and release capacity is diminished, and patients find that they improve for a few hours after taking levodopa and then the clinical benefit wears off. Ultimately, patients become dependent on a constant inŸux of levodopa into the brain, and clinical response Ÿuctuates in concert with serum levodopa. Many patients also develop choreiform, twisting-turning movements, called dyskinesia, that occur during dopamine peaks. The development of dyskinesia is related to both disease progression and exposure to medications, particularly levodopa.6-8 It is thought that exposing postsynaptic dopamine receptors to Ÿuctuating dopamine stimulation is a key factor in the development of dyskinesia.9,10 Levodopa has a serum half-life (t1/2) of approximately 60 min.11,12 It is predominantly metabolized by the enzymes dopa-decarboxylase (DDC) and catechol-O-methyltransferase (COMT).13 When orally administered by itself, only 1% of levodopa passes into the brain, and there is a high incidence of nausea and vomiting due to the peripheral formation of dopamine.14,15 When levodopa is combined with a DDC inhibitor such as carbidopa, the half-life of levodopa is extended to approximately 90 min, and the incidence of nausea and vomiting is greatly reduced.16-18 Approximately 5%-10% of orally administered levodopa reaches the brain when it is administered with a DDC inhibitor.19.

Original languageEnglish (US)
Title of host publicationParkinson's Disease, Second Edition
PublisherCRC Press
Pages839-846
Number of pages8
ISBN (Electronic)9781439807156
ISBN (Print)9781439807149
DOIs
StatePublished - Jan 1 2012

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Levodopa
Parkinson Disease
Dopamine
Dopa Decarboxylase
Therapeutics
Half-Life
Dopaminergic Neurons
Dyskinesias
Nausea
Vomiting
Brain
Catechol O-Methyltransferase Inhibitors
Serum
Carbidopa
Antiparkinson Agents
Corpus Striatum
Catechol O-Methyltransferase
Hypokinesia
Incidence
Dopamine Receptors

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)
  • Medicine(all)

Cite this

Wahba, M., Zesiewicz, T. A., & Hauser, R. A. (2012). Catechol-O-methyltransferase inhibitors in the treatment of Parkinson’s disease. In Parkinson's Disease, Second Edition (pp. 839-846). CRC Press. https://doi.org/10.1201/b12948

Catechol-O-methyltransferase inhibitors in the treatment of Parkinson’s disease. / Wahba, Mervat; Zesiewicz, Theresa A.; Hauser, Robert A.

Parkinson's Disease, Second Edition. CRC Press, 2012. p. 839-846.

Research output: Chapter in Book/Report/Conference proceedingChapter

Wahba, M, Zesiewicz, TA & Hauser, RA 2012, Catechol-O-methyltransferase inhibitors in the treatment of Parkinson’s disease. in Parkinson's Disease, Second Edition. CRC Press, pp. 839-846. https://doi.org/10.1201/b12948
Wahba M, Zesiewicz TA, Hauser RA. Catechol-O-methyltransferase inhibitors in the treatment of Parkinson’s disease. In Parkinson's Disease, Second Edition. CRC Press. 2012. p. 839-846 https://doi.org/10.1201/b12948
Wahba, Mervat ; Zesiewicz, Theresa A. ; Hauser, Robert A. / Catechol-O-methyltransferase inhibitors in the treatment of Parkinson’s disease. Parkinson's Disease, Second Edition. CRC Press, 2012. pp. 839-846
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