enquiriescyprotexcom In vitro ADME PK Monoamine Oxidase MAO Inhibition Background Information 149 Monoamine oxidases MAO are membraneassociated enzymes located speci31cally to the out ID: 942450
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To nd out more contact enquiries@cyprotex.com In vitro ADME & PK Monoamine Oxidase (MAO) Inhibition Background Information • Monoamine oxidases (MAO) are membrane-associated enzymes located speci cally to the outer mitochondrial membrane. They are the major enzymes participating in the catabolism of monoamine neurotransmitters and related exogenous amines. • Two isoforms of MAO exist, MAO-A and MAO-B, which differ in their substrate speci city, inhibitor selectivity and tissue distribution. • Selective MAO-A inhibitors are useful in the therapy of depression and anxiety whereas MAO-B inhibitors are often used in the treatment of Parkinson’s and Alzheimer’s • Cyprotex’s MAO inhibition assay identi es if your compound is an inhibitor for either MAO-A or MAO-B. Protocol ‘In human brain the predominant form is MAO-B, expressed at highest levels in astrocytes and serotonergic neurons, while MAO-A is expressed at highest levels in catecholaminergic neurons.’ 1 Hotamisligil GS and Breake eld XO (1991) Am J Hum Genet 49(2) ; 383–392 Substrate Kynuramine Metabolite 4-hydroxyquinolinol Test Article Concentrations 0, 0.4, 1, 4, 10, 40 and 100 µM (different concentrations av
ailable) Enzyme Source hMAO-A and hMAO-B expressed enzymes (Supersomes TM ) Test Article Requirements 100 µL of a 40 mM DMSO solution (or equivalent amount in solid) Positive Control Clorgyline MAO-A Selegiline MAO-B Analysis Method LC-MS/MS Data Delivery IC 50 Standard error of IC 50 % Control at each concentration Monoamine Oxidase (MAO) is a critical enzyme in the degradative deanimation of biogenic amines throughout the body 1 . Figure 1 Inhibitory speci city demonstrated for MAO-A inhibitor clorgyline using MAO-A or MAO-B expressed enzyme and kynuramine as the substrate. Figure 2 Inter-assay reproducibility of MAO-B inhibition using speci c MAO-B inhibitor selegiline and non-speci c inhibitor tranylcypromine. Each inhibitor was investigated on three separate occasions using hMAO-B expressed enzyme and kynuramine as substrate. The error bars represent the stadard error of the IC 50 determination. References 1 Hotamisligil GS and Breake eld XO (1991) Human monoamine oxidase A gene determines levels of enzyme activity. Am J Hum Genet 49(2) ; 383-392 0.000010.00010.0010.010.11020406080100 120% ControlClorgyline concentration (Clorgyline MAO-A Clorgyline MAO-B 00.10.20.30.4 0.5IC 50 ( TranylcypromineSelegilineAssay 1Assay 2Assay 3