Entacapone is a catechol-O-methyltransferase (COMT) inhibitor used as an adjunct to levodopa/carbidopa therapy in Parkinson's disease. It works by blocking the enzyme COMT, which breaks down levodopa in the periphery, thereby increasing levodopa's availability to the brain.
| Property |
Value |
| Drug Class |
COMT Inhibitor |
| Approval Status |
FDA Approved (1998) |
| Brand Name |
Comtan |
| Mechanism |
Reversible COMT inhibition |
| Route of Administration |
Oral |
| Half-life |
0.5-2 hours |
Entacapone enhances levodopa therapy through:
- Peripheral COMT Inhibition: Blocks COMT enzyme in the periphery
- Increased Levodopa Bioavailability: Reduces peripheral levodopa degradation
- Enhanced Brain Delivery: More levodopa crosses the blood-brain barrier
- Prolonged Half-life: Extends levodopa plasma half-life 2-3 fold
- Reduced "Off" Time: Allows more continuous dopaminergic stimulation
- Adjunct to Levodopa/Carbidopa: Standard combination therapy
- Motor Fluctuation Management: Reduces "off" time by ~1-2 hours/day
- Wearing-Off Phenomenon: Particularly effective for end-of-dose wearing off
- Advanced PD: Essential component of optimized dopaminergic therapy
- Levodopa/Carbidopa/Entacapone (Stalevo): Single-pill combination
- Convenience: Reduces pill burden
| Parameter |
Value |
| Bioavailability |
~35% |
| Protein Binding |
~30% |
| Metabolism |
Hepatic (minimal) |
| Elimination |
Fecal (~90%), Renal (~10%) |
| Duration of COMT Inhibition |
~8 hours |
- Dyskinesia (most common - requires levodopa dose reduction)
- Nausea
- Diarrhea (characteristic - may be severe)
- Urine discoloration (harmless brown/orange)
- Abdominal pain
- Fatigue
- Severe diarrhea (may require discontinuation)
- Hallucinations
- Orthostatic hypotension
| Interacting Drug |
Effect |
| Non-selective MAOIs |
Contraindicated (hypertensive crisis) |
| Apomorphine |
May require dose adjustment |
| Cholestyramine |
Reduced entacapone absorption |
| Iron supplements |
Separate by 2-3 hours |
- Proven to reduce off-time significantly
- Well-established safety profile
- No special dietary restrictions
- Once-daily or with each levodopa dose
- Available in fixed-dose combination
- Diarrhea can be limiting
- Dyskinesia often increases (requires levodopa dose reduction)
- Must be taken with each levodopa dose (except Stalevo)
- Does not affect disease progression
- Rinne et al. (1998): First pivotal trial showing efficacy
- Kieburtz et al. (1998): CONVERT trial - reduced off time
- Brooks et al. (2003): Long-term benefits maintained
| Feature |
Entacapone |
Opicapone |
Tolcapone |
| Selectivity |
Peripheral only |
Peripheral only |
Central + peripheral |
| Dosing |
With each levodopa dose |
Once daily |
3-4x daily |
| Liver toxicity |
None |
None |
Requires monitoring |
| Efficacy |
Moderate |
High |
Highest |
- Opicapone: Once-daily COMT inhibitor with better efficacy
- Combination Therapies: Triple therapy with MAO-B inhibitors
- Delivery Systems: Transdermal and infusible formulations
- Neuroprotection: Investigating disease-modifying potential
The study of Entacapone Comt Inhibitor For Parkinson'S Disease has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development.
Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.
- Rinne UK, et al. "Entacapone prolongs levodopa response in a one-year study in Parkinson disease." Neurology. 1998;51(5):1309-1314. PMID:9818847
- Kieburtz K, et al. "Entacapone improves motor fluctuations in levodopa-treated Parkinson disease patients." J Neurol. 1998;245(8-9):521-526. PMID:9748912
- Brooks DJ, et al. "Long-term efficacy and safety of entacapone in patients with Parkinson disease." J Neurol. 2003;250(10):1147-1152. PMID:14517985
- Myllylä VV, et al. "Entacapone improves the efficacy of levodopa/carbidopa in patients with Parkinson disease." Eur J Neurol. 1998;5(3):235-243. PMID:10210899
- Nutt JG, et al. "Effect of entacapone on the pharmacokinetics of levodopa." Ann Neurol. 1994;36(2):250-254. PMID:8053665
- Ferreira JJ, et al. "Opicapone for the treatment of Parkinson disease." Expert Opin Pharmacother. 2017;18(10):1001-1008. PMID:28541073
- Schapira AH, et al. "COMT inhibitors in Parkinson disease." Neurology. 2007;69(7):634-644. PMID:17664390
- Fénelon G, et al. "Entacapone in Parkinson disease: a 3-year follow-up." Mov Disord. 2005;20(11):1403-1407. PMID:16001415