Treatments: COMT
Inhibitors

Names:
Entacapone
- Tolcapone (Tasmar, recently approved by FDA in 1997)
How They Work:
COMT inhibitors (short for
catechol-O-methyltransferase) are a rather newly developed line of defense against
Parkinson's Disease. Although similar to MAO-B inhibitors that work by preventing
the breakdown of dopamine by MAO-B enzymes, the COMT inhibitor tolcapone prevents
the breakdown of both dopamine and L-dopa by COMT enzymes in both the central and
peripheral nervous system (Entacapone cannot cross the blood-brain barrier, and
only works peripherally). Administration of COMT inhibitors increases the availability of
dopamine and L-dopa in the body, increases the concentration of dopamine, and increases
the effectiveness of L-dopa treatments (because the introduced L-dopa is not broken
down before it reaches the brain). The COMT enzymes that would break down
the dopamine in the brain are also disabled by the inhibitor drug, and so dopamine
successfully stimulates the necessary neurons to control motor functions that are
inactive in patients with Parkinson's. Therefore, a higher percentage of the L-dopa
administered to a patient is used by the body, and less of a dose is needed to
maintain the same level of treatment. Decreasing the dosage often reduces the diskinesias
associated with L-dopa.
In clinical trials of one of these drugs, trade-named Tasmar (generic name tolcapone),
patients with a stable response to L-dopa showed significant improvements in daily skills
like walking and writing (Henkel 1998). After one year, their improvements remained stable.
The side effects may include DID, but this can be avoided by decreasing L-dopa dosage
(Gregory 1999).
Side-Effects:
Interferes with metabolism of other chemicals by COMT enzyme, such as brochodilators, dopamine agonists, and antihypertensives
- Muscle cramps
- Dystonia
- Diarrhea
- Headache
- Nausea and vomiting
- Sleep disorders
- Faintness
- Confusion
- Anxiety
- Some dyskinesia
- Urine discoloration
Information from:
Parkinson's Disease at Harvard
http://www.psychweekly.com/aspx/Article/articledetail.aspx?articleid=617
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