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

Expert Opin Drug Metab Toxicol. 2019 May;15(5):429-435. doi: 10.1080/17425255.2019.1607292. Epub 2019 Apr 24.

Abstract

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; rasagiline; safinamide; selegiline.

Publication types

  • Review

MeSH terms

  • Antiparkinson Agents / administration & dosage*
  • Antiparkinson Agents / pharmacokinetics
  • Disease Progression
  • Dopamine / metabolism
  • Humans
  • Levodopa / administration & dosage
  • Monoamine Oxidase / drug effects
  • Monoamine Oxidase / metabolism
  • Monoamine Oxidase Inhibitors / administration & dosage*
  • Monoamine Oxidase Inhibitors / pharmacokinetics
  • Parkinson Disease / drug therapy*
  • Parkinson Disease / physiopathology
  • Severity of Illness Index

Substances

  • Antiparkinson Agents
  • Monoamine Oxidase Inhibitors
  • Levodopa
  • Monoamine Oxidase
  • Dopamine