How Do COMT Inhibitors Work?

Catechol-O-methyltransferase (COMT) inhibitors are a class of medications that prolongs the effect of levodopa by inhibiting its breakdown.

The direct cause of Parkinson's disease or Parkinsonian-like syndrome is the deficiency of the neurotransmitter dopamine in the brain. Antiparkinson medicines aim to prolong the action of dopamine in the brain by:

• Replacing dopamine
• Inhibiting dopamine breakdown
• Sensitizing dopamine receptors to stimulate dopamine release

COMT inhibitors do not directly treat the symptoms but prolong the effect of the drug levodopa by inhibiting its breakdown. Thus, COMT inhibitors prolong the half-life of levodopa and prevent motor fluctuations. Motor fluctuations occur as a part of disease progression in people with Parkinson’s disease. It refers to changes in the ability to move characterized by on-off times. When levodopa begins to take effect, there is an ON time when a person can move and function well. On the other hand, a person may notice difficulty in movement when the drug effect wears off, called OFF time. COMT inhibitors maintain the dopamine concentration even when the effect of levodopa wears off, thereby preventing motor fluctuations.

COMT inhibitors are given with levodopa/carbidopa to reduce OFF episodes in people with Parkinson’s disease.

The most common side effects of COMT inhibitors include:

• Constipation
• Low blood pressure
• Syncope (blackout)
• Decreased weight
• Dry mouth
• Dizziness
• Hallucinations
• Nausea
• Diarrhea
• Urine discoloration
• Risk of liver damage
• Confusion
• Dyskinesia (uncontrolled, involuntary movements)

The information contained herein is not intended to cover all possible side effects, precautions, warnings, drug interactions, allergic reactions, or adverse effects. Check with your doctor or pharmacist to make sure these drugs do not cause any harm when you take them along with other medicines. Never stop taking your medication and never change your dose or frequency without consulting your doctor.

Generic and brand names of COMT inhibitors include:

• Comtan
• Entacapone
• Entacapone/levodopa/carbidopa
• Ongentys
• Opicapone
• Stalevo
• Tasmar
• Tolcapone