What is a COMT Inhibitor?
Entacapone (brand name Comtan) belongs to a class of medications known as catechol-O-methyltransferase (COMT) inhibitors. COMT is an enzyme found in various tissues throughout the body, including the liver and kidneys, where it is responsible for breaking down a number of substances, including levodopa. By inhibiting this enzyme, entacapone effectively prevents the premature metabolism of levodopa in the periphery (outside of the brain).
How Entacapone Works to Treat Parkinson's Disease
Parkinson's disease is characterized by a deficiency of the neurotransmitter dopamine in the brain. Levodopa is the most effective medication for replacing this lost dopamine, as it can cross the protective blood-brain barrier and be converted into dopamine in the brain. However, as the disease progresses, patients can experience "wearing-off" periods, where the effects of levodopa diminish before the next dose is due.
The Mechanism of Action
This is where entacapone plays a critical role. When levodopa is taken, some of it is metabolized by the COMT enzyme before it can reach the brain. By inhibiting this enzyme, entacapone allows more levodopa to reach the brain over a longer period. This mechanism is key for managing the "wearing-off" phenomenon and providing smoother, more consistent symptom control throughout the day.
- Increases bioavailability: By preventing peripheral breakdown, entacapone boosts the amount of levodopa that can reach the central nervous system.
- Extends half-life: The drug increases the half-life of levodopa by up to 75%, extending its effectiveness.
- Smooths out motor fluctuations: This leads to more steady levels of dopamine and better control of motor symptoms.
Entacapone vs. Tolcapone: A Comparative Look
Entacapone is not the only COMT inhibitor available for Parkinson's treatment. Tolcapone (brand name Tasmar) is another, and understanding the differences is important. Tolcapone and entacapone both inhibit the COMT enzyme, but their site of action and potential side effects differ significantly.
| Feature | Entacapone (Comtan) | Tolcapone (Tasmar) |
|---|---|---|
| Site of Action | Acts peripherally only (does not cross the blood-brain barrier). | Acts both peripherally and centrally (crosses the blood-brain barrier). |
| Hepatotoxicity Risk | Very low risk of liver damage; liver function monitoring is generally not required. | Significant risk of severe liver damage (hepatotoxicity); requires regular liver function monitoring. |
| Dosing Schedule | Must be taken with every dose of levodopa/carbidopa. | Typically taken three times a day, regardless of levodopa dosing. |
| Clinical Use | Widely used as an adjunct to levodopa to treat "wearing-off" symptoms. | Use is restricted due to liver toxicity concerns. |
How to Take Entacapone
Entacapone is always prescribed as an adjunct to levodopa and carbidopa. It is available in a separate tablet (Comtan) or as part of a combination pill containing all three medications (e.g., Stalevo). It is crucial to take entacapone with each dose of the levodopa/carbidopa medication for it to be effective. Dosing frequency can be up to eight times a day.
Common Side Effects and Considerations
As with any medication, entacapone can cause side effects. Many are related to the increased dopaminergic activity caused by enhanced levodopa effects.
- Involuntary movements (dyskinesia): The most common side effect, which may require a reduction in the levodopa dose.
- Gastrointestinal issues: Diarrhea, nausea, and abdominal pain are frequently reported. Severe diarrhea may lead to a condition called microscopic colitis and require discontinuation.
- Drowsiness: Can cause sleepiness or, in some cases, a sudden onset of sleep, even without prior warning. Caution is advised when driving or performing other tasks requiring alertness.
- Urine discoloration: It is common and harmless for entacapone to turn urine a brownish-orange color.
- Other side effects: Other potential side effects include dizziness, dry mouth, and confusion.
Drug Interactions
Entacapone should not be taken with nonselective monoamine oxidase (MAO) inhibitors, such as phenelzine, as this can increase the risk of elevated blood pressure and heart rate. It can also increase the sedative effects of other drugs that cause drowsiness, such as sedatives or narcotic pain medication.
Conclusion
In summary, entacapone is a peripheral COMT inhibitor, a specific type of drug designed to be used with levodopa/carbidopa therapy for Parkinson's disease. Its function is to prevent the breakdown of levodopa outside the brain, thereby increasing and prolonging its therapeutic effects. For patients experiencing motor fluctuations or "wearing-off" periods, entacapone is a valuable tool for providing more stable symptom control and improving quality of life, without the liver risks associated with other central-acting COMT inhibitors like tolcapone. Always consult a healthcare provider for proper diagnosis and treatment.
For more detailed prescribing information, refer to the FDA label for Comtan (entacapone).
