title: Inhibitor design for monoamine oxidases.
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.
authors.affiliation: Biomedical Sciences Research Complex, University of St Andrews, Biomolecular Sciences Building, North Haugh, St Andrews, KY16 9ST, UK. rrr@st-and.ac.uk
authors.forename: Rona R
authors.initials: RR
authors.lastname: Ramsay
mesh_terms: D001665:Binding Sites; D015195:Drug Design; D006801:Humans; D007700:Kinetics; D008958:Models, Molecular; D015394:Molecular Structure; D008995:Monoamine Oxidase / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008996:Monoamine Oxidase Inhibitors / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use; D013379:Substrate Specificity
chemical_list: D008996:Monoamine Oxidase Inhibitors; D008995:Monoamine Oxidase