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• W3030853041 abstract "Overdose is the main cause of mortality among heroin users. Many of these overdose-induced deaths can be prevented through the timely administration of naloxone (NLX), a nonselective mu (μ)-, kappa (κ)-, and delta (δ)-opioid receptor antagonist. NLX competitively inhibits opioid-overdose-induced respiratory depression without eliciting any narcotic effect itself. The aim of this study was to investigate the antagonistic action of NLX by comparing its distribution to that of 6-monacetylmorphine (6-MAM), heroin’s major metabolite, in a rodent model using mass spectrometric imaging (MSI) in combination with liquid chromatography–tandem mass spectrometry (LC–MS/MS). Male Sprague–Dawley rats (n = 5) received heroin (10 mg kg–1) intraperitoneally, NLX (10 mg kg–1) intranasally, and NLX injected intranasally 5 min after heroin administration. The animals were sacrificed 15 min after dose and brain tissues were harvested. The MSI image analysis showed a region-specific distribution of 6-MAM in the brain regions including the corpus callosum, hippocampal formation, cerebral cortex, corticospinal tracts, caudate putamen, thalamus, globus pallidus, hypothalamus, and basal forebrain regions of the brain. The antagonist had a similar biodistribution throughout the brain in both groups of animals that received NLX or NLX after heroin administration. The MSI analysis demonstrated that the intensity of 6-MAM in these brain regions was reduced following NLX treatment. The decrease in 6-MAM intensity was caused by its displacement by the antagonist and its binding to these receptors in these specific brain regions, consequently enhancing the opioid elimination. These findings will contribute to the evaluation of other narcotic antagonists that might be considered for use in the treatment of drug overdose via MSI." @default.
• W3030853041 created "2020-06-05" @default.
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• W3030853041 date "2020-05-27" @default.
• W3030853041 modified "2023-10-18" @default.
• W3030853041 title "Mass Spectrometric Imaging of the Brain Demonstrates the Regional Displacement of 6-Monoacetylmorphine by Naloxone" @default.
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• W3030853041 doi "https://doi.org/10.1021/acsomega.9b03570" @default.
• W3030853041 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/7288357" @default.
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