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COMT Inhibitors: Novel Treatments for Parkinson's Disease

Published online by Cambridge University Press:  07 November 2014

Charles H. Adler
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Abstract

Catechol-O-methyltransferase (COMT) inhibitors are a new class of medication being developed for the treatment of Parkinson's disease (PD). The enzyme COMT metabolizes levodopa and dopamine, both peripherally and centrally. Coadministration of a COMT inhibitor with levodopa creates an increase in peripheral and central levodopa bioavailability, as well as higher central dopamine concentrations. Because these actions improve the duration of response to levodopa, the COMT inhibitors should prove to be useful adjunctive therapies in PD patients.

Type
Feature Articles
Information
CNS Spectrums , Volume 3 , Issue 2: Pathophysiologic and Clinical Progress in Parkinson's Disease , February 1998 , pp. 53 - 56
Copyright
Copyright © Cambridge University Press 1998

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References

REFERENCES

1.Ahlskog, JE. Treatment of early Parkinson's disease: are complicated strategies justified? Mayo Clin Proc. 1996;71:659–670.Google Scholar
2.Mannisto, PT, Kaakkola, S. Rationale for selective COMT inhibitors as adjuncts in the drug treatment of Parkinson's disease. Pharmacol Toxicol. 1990;66:317–323.Google Scholar
3.Cedarbaum, JM. Clinical pharmacokinetics of anti-parkinsonian drugs. Clin Pharmacokinet. 1987;13:141–178.CrossRefGoogle ScholarPubMed
4.Waters, CH. Managing the late complications of Parkinson's disease. Neurology. 1997;49(suppl 1):S49–S57.Google Scholar
5.Nutt, JG, Woodward, WR, Beckner, RM, et al.Effect of peripheral catechol-O-methyltransferase inhibition on the pharmacokinetics and pharmacodynamics of levodopa in parkinsonian patients. Neurology. 1994;44:913–919.Google Scholar
6.Mannisto, PK. Clinical potential of catechol-O-methyltransferase (COMT) inhibitors as adjuvants in Parkinson's disease. CNS Drugs. 1994;1:172–179.Google Scholar
7.Muenter, MD, Dinapoli, RP, Sharpless, NS, Tyce, GM. 3-0-methyldopa, L-dopa, and trihexyphenidyl in the treatment of Parkinson's disease. Mayo Clin Proc. 1973;48:173–183.Google Scholar
8.Reches, A, Mielke, LR, Fahn, S. 3-O-methyldopa inhibits rotations induced by levodopa in rats after unilateral destruction of the nigrostriatal pathway. Neurology. 1982;32:887–888.CrossRefGoogle ScholarPubMed
9.Cedarbaum, JM, Kutt, H, McDowell, FH. Clinical significance of the relationship between O-methyldopa levels and levodopa intake. Neurology. 1988;38:533–536.Google Scholar
10.Dingemanse, J, Jorga, KM, Schmitt, M, et al.Integrated pharmacokinetics and pharmacodynamics of the novel catechol-O-methyltransferase inhibitor tolcapone during first administration to humans. Clin Pharmacol Ther. 1995;57:508–517.Google Scholar
11.Ericsson, AD. Potentiation of the L-dopa effect in man by the use of cateehoi-O-metbyltransferase inhibitors. J Neurol Sci. 1971;14:193–197.Google Scholar
12.Ruottinen, HM, Rinne, UK. Entacapone prolongs levodopa response in a one month double blind study in parkinsonian patients with levodopa related fluctuations. J Neurol Neurosurg Psychiatry. 1996;60:36–40.Google Scholar
13.Cedarbaum, JM, Kutt, H, Dhar, AK, Watkins, S, McDowell, FH. Effect of supplemental carbidopa on bioavailability of L-dopa. Clin Neuropharmacol. 1986;9:153–159.Google Scholar
14.Mannisto, PT, Tuomainen, P, Touminen, RK. Different in vivo properties of three new inhibitors of catechol-O-methyltransferase in the rat. Br J Pharmacol. 1992;105:569–574.CrossRefGoogle ScholarPubMed
15.Parkinson Study Group. Entacapone improves motor fluctuations in levodopa-treated Parkinson's disease patients. Ann Neurol. 1997;42:747–755.Google Scholar
16.Roberts, JW, Cora-Locatelli, G, Bravi, D, Amantea, MA, Mouradian, MM, Chase, TN. Catechol-O-methyltransferase inhibitor tolcapone prolongs levodopa/carbidopa action in parkinsonian patients. Neurology. 1993;43:2685–2688.Google Scholar
17.Kurth, MC, Adler, CH, Hilaire, M, et al, for the Tolcapone Fluctuator Study Group. Tolcapone improves motor function and reduces levodopa requirement in patients with Parkinson's disease experiencing motor fluctuations: a multicenter, double-blind, randomized, placebo-controlled trial. Neurology. 1997;48:81–87.Google Scholar
18.Rajput, AH, Martin, W, Saint-Hilaire, M, Dorflinger, E, Pedder, S. Tolcapone improves motor function in parkinsonian patients with the “wearing-off” phenomenon: a double-blind, placebo-controlled, multicenter trial. Neurology. 1997;49:1066–1071.CrossRefGoogle ScholarPubMed
19.Waters, CH, Kurth, M, Bailey, P, et al, for the Tolcapone Stable Study Group. Tolcapone in stable Parkinson's disease: efficacy and safety of long-term treatment. Neurology. 1997;49:665–671.Google Scholar
20.Agid, Y, Destee, A, Durif, F, Montastruc, JL, Pollak, P, for the French Tolcapone Study Group. Tolcapone, bromocripline, and Parkinson's disease. Lancet. 1997;350:712–713.CrossRefGoogle ScholarPubMed