Pharmacokinetics of monoamine oxidase B inhibitors in Parkinson’s disease: current status

ABSTRACT

Introduction: Brain function depends considerably on the neurotransmission of biogenic monoamines. Their metabolism employs monoamine oxidase-B in neuronal and glial cells. Inhibition of monoamine oxidase-B elevates biogenic amine levels. Accordingly, monoamine oxidase-B inhibitors provide a symptomatic effect via dopamine on motor symptoms in patients with Parkinson’s disease.

Areas covered: This narrative review aims to describe the pharmacokinetic characteristics of the available reversible and irreversible monoamine oxidase B inhibitors for the treatment of Parkinson’s disease in daily practice. All these compounds are administered on a daily basis.

Expert opinion: Reversibility or irreversibility of available monoamine oxidase-B inhibition is not relevant, due to their daily intake and half-life in clinical practice. Irreversible monoamine oxidase-B inhibitors slowed the progression of neuronal dying in experimental models of Parkinson’s disease. In patients, concomitant inhibition of monoamine oxidase-B caused less increase of levodopa dosages over five years. The curve of levodopa increment diverged from the placebo curve. This reduced need for L-dopa monotherapy may be discussed as an indirect biomarker for disease severity and reflects a disease-modifying effect. In case of a symptomatic effect only, parallel curves would have occurred. Long-term L-dopa treatment should be combined with monoamine oxidase-B inhibitors when tolerated by patients.

KEYWORDS:

• Monoamine oxidase
• selegiline
• rasagiline
• safinamide

Article highlights

• Irreversible inhibitors of monoamine oxidase-B are selegiline, rasagiline.

• Safinamide blocks monoamine oxidase–B only in a reversible fashion.

• Inhibitors of monoamine oxidase-B lower dopamine degradation

• Selegiline, rasagiline, and safinamide ameliorate motor impairment in patients with Parkinson’s disease, when applied daily.

• Experimental research showed that inhibition of monoamine oxidase-B-activity weakened chronic neurodegeneration.

• Oxidative stress results from elevated biogenic amine turnover via the monoamine oxidase B and contributes to disease progression.

• One long-term selegiline trial showed in comparison with placebo therapy a less need for levodopa monotherapy as indirect biomarker for disease progression.

This box summarizes key points contained in the article.

Declaration of interest

TM was involved as principal investigator in clinical trials with safinamide and rasagiline. TM received honoraria for lectures, advisory boards, Consulting activities for TEVA, Zambon, Merck. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This manuscript was not funded.