The secret of Opicapone’s mechanism of action: professional analysis of how it works

Opicapone is a new type of long-acting catechol-O-methyltransferase (COMT) inhibitor. Its main mechanism of action is to block the activity of peripheral COMT enzyme, thereby reducing the degradation of levodopa in peripheral tissues, increasing its concentration into the brain, and making its effect in the nigrostriatal pathway more durable, so as to improve the motor symptoms of patients with Parkinson's disease.

Levodopa is the most commonly used drug in the treatment of Parkinson's disease. It is converted into dopamine after entering the brain, replenishing dopamine levels reduced due to neuron loss. However, after oral administration of levodopa, less than 10% of the drug can successfully pass through the blood-brain barrier and enter the central nervous system, and most of it is degraded in peripheral tissues and metabolized mainly through two enzyme pathways: dopa decarboxylase (DDC) and catechol-O-methyltransferase (COMT). In order to reduce the peripheral degradation of levodopa, DDC inhibitors (such as carbidopa) and COMT inhibitors (such as opicapone) are usually used in combination clinically.

The main effect of Opicapone is to irreversibly inhibitCOMT enzyme activity, thereby reducing the peripheral degradation of levodopa into 3-O-methyldopa (3-OMD). Since the increase of 3-OMD may be related to the occurrence of the "off period" phenomenon, by inhibiting COMT, Opicapone can reduce the production of 3-OMD, allowing levodopa to function more stably and permanently, reducing motor fluctuations in patients with Parkinson's disease and improving the quality of life.

What makes Opicapone unique is its long-acting effect. Compared with traditionalCOMT inhibitors such as Entacapone, Opicapone has a longer half-life and therefore only needs to be taken once a day. In addition, it has low penetration into the central nervous system, so it mainly acts in the periphery, reducing central-related side effects such as anxiety, hallucinations, etc.

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