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• W2341020019 abstract "2-Arachidonoylglycerols (2-AG) is one of the major endocannabinoids in the central nervous system. Upregulation of central endocannabinoids signaling by selective inhibition of brain monoacylglycerol lipase (MAGL) activity is a potential therapeutic approach in pain, obesity, and diabetes modulation to name a few. Thus, a sensitive and reliable analytical method for determination of endocannabinoid levels in the brain is essential for the discovery of MAGL inhibitors. Accurate measurement of monoacylglycerols (MAG) levels, using liquid chromatography positive electrospray ionization mass spectrometry (LC / +ESI / MS) and tandem MS, is a challenge since the brain endocannabinoids are not only susceptible to stress in the in-life phase of the study, but also prone to postmortem metabolism, acyl migration (i.e., conversion from 2-MAG to 1(3)-MAG), metal adduct ion formation and chemical hydrolysis generating the same products as those by the target enzyme. To avoid these artifacts, we have developed a simple LC / +ESI / MS method for direct detection of ammonium-adduct cations of the major MAGs in selected ion monitoring mode (SIM). For the in vitro MAGL inhibition assay, a LC isocratic elution was used for baseline separation of MAGs and their acyl migration isomers produced during the 37oC incubation with rat brain homogenate. To minimize the postmortem metabolism and isomerization of MAGs for in-vivo studies, rat brain was homogenized directly in four milliliters of ethanol for every gram of brain tissue and a linear LC gradient elution was applied for broad endocannabinoid profiling. The SIM LC / +ESI / MS method is shown to be useful for in-vitro brain evaluation of inhibitory potency of MAGL and fatty acid amide hydrolase (FAAH) inhibitors and for in-vivo brain assessment for target engagement studies." @default.
• W2341020019 created "2016-06-24" @default.
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• W2341020019 date "2015-01-01" @default.
• W2341020019 modified "2023-10-16" @default.
• W2341020019 title "Profiling Rat Brain Monoacylglycerol Lipase Activity Using an Ammonia- Adduct Enhanced Selected Ion Monitoring Liquid-Chromatography Positive Electrospray Ionization Mass Spectrometry Assay" @default.
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• W2341020019 doi "https://doi.org/10.4172/2153-2435.1000470" @default.
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