The mechanism of entacapone/codan in the treatment of Parkinson's disease

Entacapone is a commonly used auxiliary drug in the treatment of Parkinson's disease. Its core mechanism of action is mainly achieved by inhibiting catechol-O-methyltransferase (COMT) in peripheral tissues. COMT is an important enzyme that catalyzes the peripheral metabolism of levodopa. It can convert levodopa into 3-O-methyldopa, thereby reducing the effective concentration of levodopa entering the central nervous system. When patients with Parkinson's disease use levodopa alone, their plasma dopamine levels fluctuate greatly, leading to clinical manifestations of an "on-off" phenomenon, that is, unstable symptom control. The combined use of entacapone can inhibit the peripheral metabolism of levodopa, increase its plasma concentration and duration, make the drug's dopamine level in the brain more constant, and thereby improve motor function.

In clinical practice, entacapone is often used in combination with levodopa and aromatic amino acid decarboxylase inhibitors such as carbidopa or benserazide. Studies have shown that this combination regimen results in higher and more sustained plasma levels of levodopa than levodopa and a decarboxylase inhibitor alone, thereby prolonging the effective effect of levodopa. In the brain, this means dopaminergic neurons receive more sustained stimulation, reducing fluctuations in motor symptoms and significantly alleviating the tremors, stiffness and bradykinesia seen in Parkinson's disease.

In addition, entacapone stabilizes the pharmacokinetics of levodopa, allowing the clinical dosing interval of levodopa to be more balanced and reducing the need for patients to frequently adjust the dosage due to fluctuations in symptoms. The guidelines point out that this effect not only improves motor symptoms, but also improves the patient's quality of life, giving patients more autonomy and predictability in daily activities. Its unique mechanism makes it an important adjuvant treatment option for patients with mid-to-late stage Parkinson's disease, especially for patients with "disappearance of levodopa effect" or obvious "on-off phenomenon".

Reference materials:https://www.drugs.com/mtm/comtan.html