Which medications in the drug class COMT Inhibitors are used in the treatment of Parkinson Disease?

Updated: Jan 24, 2019
  • Author: Robert A Hauser, MD, MBA; Chief Editor: Selim R Benbadis, MD  more...
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Answer

COMT Inhibitors

Catechol-O -methyl transferase (COMT) inhibitors inhibit the peripheral metabolism of levodopa, making more levodopa available for transport across the blood-brain barrier over a longer time. For patients with motor fluctuations on levodopa/carbidopa, the addition of a COMT inhibitor decreases off time, improves motor function, and allows lower levodopa doses.

Tolcapone (Tasmar)

Tolcapone is an adjunct to levodopa/carbidopa therapy in PD in patients who are experiencing motor fluctuations. Because of the risk of hepatotoxicity, tolcapone is reserved for patients who have not responded adequately to, or are not appropriate candidates for, other adjunctive medications. If improvement is not apparent within 3 weeks, this medication should be withdrawn.

Tolcapone is a selective and reversible inhibitor of COMT. In the presence of a decarboxylase inhibitor such as carbidopa, COMT is the major degradation pathway for levodopa. By inhibiting COMT, there are more sustained plasma levels of levodopa, as well as enhanced central dopaminergic activity.

Entacapone (Comtan)

Entacapone is approved as an adjunct to levodopa/carbidopa for patients who are experiencing signs and symptoms of end-of-dose "wearing-off." The mechanism of action of entacapone is related to its ability to inhibit COMT and alter plasma pharmacokinetics of levodopa. When given in conjunction with levodopa and an aromatic amino acid decarboxylase inhibitor (eg, carbidopa), plasma levels of levodopa are more sustained than after administration of levodopa and an aromatic amino acid decarboxylase inhibitor alone. These sustained plasma levels of levodopa may result in more constant dopaminergic stimulation in the brain. This may lead to greater effects on signs and symptoms of PD, as well as increased levodopa adverse effects (which sometimes require a levodopa dose decrease).

Carbidopa, levodopa, and entacapone (Stalevo)

Carbidopa/levodopa/entacapone is indicated for the treatment of PD to substitute (with equivalent strengths of each of the 3 components) for immediate-release carbidopa/levodopa and entacapone previously administered as individual products. It is also used to replace immediate-release carbidopa/levodopa therapy (without entacapone) when patients experience the signs and symptoms of end-of-dose "wearing-off" (only for patients taking a total daily dose of levodopa of 600 mg or less and not experiencing dyskinesias).

Carbidopa inhibits dopa decarboxylation, thereby allowing more complete levodopa distribution to the CNS. Levodopa is a dopamine precursor capable of crossing the blood-brain barrier, thereby increasing CNS dopamine following conversion. Entacapone inhibits COMT, another enzyme that metabolizes levodopa. COMT inhibition increases and sustains levodopa plasma levels, enabling more blood-brain barrier penetration.


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