Clinical benefit of MAO-B and COMT inhibition in Parkinson's disease: practical considerations

by Selleckchem | Apr 16 2023

Inhibitors of monoamine oxidase B (MAO-B) and catechol-O-methyltransferase (COMT) are major strategies to reduce levodopa degradation and thus to increase and prolong its effect in striatal dopaminergic neurotransmission in Parkinson's disease patients. While selegiline/rasagiline and tolcapone/entacapone have been available on the market for more than one decade, safinamide and opicapone have been approved in 2015 and 2016, respectively. Meanwhile, comprehensive data from several post-authorization studies have described the use and specific characteristics of the individual substances in clinical practice under real-life conditions. Here, we summarize current knowledge on both medication classes, with a focus on the added clinical value in Parkinson's disease. Furthermore, we outline practical considerations in the treatment of motor fluctuations and provide an outlook on ongoing studies with MAO-B and COMT inhibitors.

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Monoamine oxidase B (MAO-B) inhibitors and catechol-O-methyltransferase (COMT) inhibitors are important strategies for managing motor fluctuations in Parkinson's disease (PD) patients. By inhibiting the degradation of levodopa, they can increase and prolong its effects in striatal dopaminergic neurotransmission. There are several drugs available on the market that target these enzymes, including selegiline, rasagiline, tolcapone, entacapone, safinamide, and opicapone.

Selegiline and rasagiline are selective irreversible inhibitors of MAO-B, and they have been available for more than a decade. They are typically used as adjunct therapy to levodopa in early and advanced PD. Clinical studies have demonstrated that they can reduce the frequency of motor fluctuations and dyskinesia, as well as improve motor function and quality of life.

Tolcapone and entacapone are reversible inhibitors of COMT, and they have also been available for more than a decade. They are used as adjunct therapy to levodopa in advanced PD to reduce motor fluctuations. Tolcapone is associated with a risk of hepatotoxicity, and its use is therefore restricted in many countries. Entacapone is generally well-tolerated, but it may cause diarrhea, nausea, and abdominal pain.

Safinamide and opicapone are more recent additions to the MAO-B and COMT inhibitor classes, respectively. Safinamide is a selective, reversible inhibitor of MAO-B, with additional effects on glutamate release and reuptake. It has been approved for use as adjunct therapy to levodopa in mid-to-late stage PD. Clinical studies have shown that safinamide can reduce "off" time, improve motor function, and improve quality of life. It is generally well-tolerated, but it may cause dyskinesia and falls.

Opicapone is a reversible inhibitor of COMT, with a longer half-life than entacapone. It has been approved for use as adjunct therapy to levodopa in mid-to-late stage PD. Clinical studies have shown that opicapone can reduce "off" time and improve motor function, with a similar safety profile to entacapone.

In clinical practice, the choice of MAO-B or COMT inhibitor depends on the individual patient's needs and preferences. MAO-B inhibitors may be preferred in patients with early PD or mild motor fluctuations, while COMT inhibitors may be preferred in patients with advanced PD or more severe motor fluctuations. Combination therapy with both types of inhibitors may also be considered in some cases.

It is important to monitor patients for adverse effects and adjust therapy as needed. In addition, patients should be educated on the proper timing and dosing of their medications to optimize their effects and minimize side effects.

Ongoing studies are exploring new formulations and combinations of MAO-B and COMT inhibitors, as well as their use in earlier stages of PD and in non-motor symptoms. These studies may provide further insights into the optimal use of these medications in the management of PD.