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

EXPERT OPINION ON DRUG METABOLISM & TOXICOLOGY(2019)

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摘要
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.
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关键词
Monoamine oxidase,selegiline,rasagiline,safinamide
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