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• W2078206080 endingPage "2292" @default.
• W2078206080 startingPage "2288" @default.
• W2078206080 abstract "Benzodiazepines probably exert their anxiolytic, hypnotic, and anticonvulsant effects by interacting with brain-specific high-affinity benzodiazepine receptors. In searching for possible endogenous ligands for these receptors we have purified a compound 10(7)-fold from human urine by extractions, treatment with hot ethanol, and column chromatography. The compound was identified as beta-carboline-3-carboxylic acid ethyl ester (IIc) by mass spectrometry, NMR spectrometry, and synthesis; IIc was also isolated from brain tissues (20 ng/g) by similar procedures. Very small concentrations of IIc displaced [3H]diazepam completely from specific cerebral receptors, but not from liver and kidney binding sites; the concentration causing 50% inhibition of specific [3H]diazepam binding (IC50) was 4-7 nM compared to ca. 5 nM for the potent benzodiazepine lorazepam. Specific binding sites for quinuclidinyl benzilate, naloxone, spiroperidol, serotonin, muscimol, and WB 4101 were not affected by IIc. In contrast to benzodiazepines, IIc exhibits mixed type competitive inhibition of forebrain benzodiazepine receptors (negative cooperativity). We surmise that an endogenous ligand for benzodiazepine receptors may be a derivative of beta-carboline-3-carboxylic acid." @default.
• W2078206080 created "2016-06-24" @default.
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• W2078206080 date "1980-04-01" @default.
• W2078206080 modified "2023-10-18" @default.
• W2078206080 title "Urinary and brain beta-carboline-3-carboxylates as potent inhibitors of brain benzodiazepine receptors." @default.
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• W2078206080 doi "https://doi.org/10.1073/pnas.77.4.2288" @default.
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