Inhibitor design for monoamine oxidases

Rona R. Ramsay

Research output: Contribution to journalReview articlepeer-review

55 Citations (Scopus)

Abstract

Flavin-containing monoamine oxidases (MAO A and MAO B) located on the outer membrane of mitochondria oxidise amines and generate hydrogen peroxide. Inhibitors alleviate depression by increasing neurotransmitter levels in the brain. Elevation of neurotransmitters, although an established outcome, is a delicate balance because complete lack of MAO A is associated with aggression and combination of monoamine oxidase inhibitors with reuptake inhibitors can result in serotonin toxicity. MAO in the periphery is essential for protection against biogenic amines, so inhibition there is an undesirable side effect both of antidepressants and drugs for other targets. MAO also metabolizes many amine drugs, an important factor in pharmacokinetics. This review summarises the structure, assay and regulation of MAO. The importance of reliable inhibition data properly analysed for these flavoenzymes is emphasised. It describes some current drugs and how new compounds that inhibit MAO are emerging from structure-based drug design.
Original languageEnglish
Pages (from-to)2529-2539
JournalCurrent Pharmaceutical Design
Volume19
Issue number14
DOIs
Publication statusPublished - Apr 2013

Keywords

  • Anti-depressant
  • Monomine oxidase
  • Neurotransmitter levels
  • Structure-based drug design
  • covalently-bound FAD
  • steady-state kinetic analysis
  • redox state

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