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The blood-to-plasma ratio and predicted GABA(A)-binding affinity of designer benzodiazepines
PURPOSE: The number of benzodiazepines appearing as new psychoactive substances (NPS) is continually increasing. Information about the pharmacological parameters of these compounds is required to fully understand their potential effects and harms. One parameter that has yet to be described is the bl...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Springer Nature Singapore
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9715504/ https://www.ncbi.nlm.nih.gov/pubmed/36454409 http://dx.doi.org/10.1007/s11419-022-00616-y |
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author | Manchester, Kieran R. Waters, Laura Haider, Shozeb Maskell, Peter D. |
author_facet | Manchester, Kieran R. Waters, Laura Haider, Shozeb Maskell, Peter D. |
author_sort | Manchester, Kieran R. |
collection | PubMed |
description | PURPOSE: The number of benzodiazepines appearing as new psychoactive substances (NPS) is continually increasing. Information about the pharmacological parameters of these compounds is required to fully understand their potential effects and harms. One parameter that has yet to be described is the blood-to-plasma ratio. Knowledge of the pharmacodynamics of designer benzodiazepines is also important, and the use of quantitative structure–activity relationship (QSAR) modelling provides a fast and inexpensive method of predicting binding affinity to the GABA(A) receptor. METHODS: In this work, the blood-to-plasma ratios for six designer benzodiazepines (deschloroetizolam, diclazepam, etizolam, meclonazepam, phenazepam, and pyrazolam) were determined. A previously developed QSAR model was used to predict the binding affinity of nine designer benzodiazepines that have recently appeared. RESULTS: Blood-to-plasma values ranged from 0.57 for phenazepam to 1.18 to pyrazolam. Four designer benzodiazepines appearing since 2017 (fluclotizolam, difludiazepam, flualprazolam, and clobromazolam) had predicted binding affinities to the GABA(A) receptor that were greater than previously predicted binding affinities for other designer benzodiazepines. CONCLUSIONS: This work highlights the diverse nature of the designer benzodiazepines and adds to our understanding of their pharmacology. The greater predicted binding affinities are a potential indication of the increasing potency of designer benzodiazepines appearing on the illicit drugs market. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s11419-022-00616-y. |
format | Online Article Text |
id | pubmed-9715504 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Springer Nature Singapore |
record_format | MEDLINE/PubMed |
spelling | pubmed-97155042022-12-03 The blood-to-plasma ratio and predicted GABA(A)-binding affinity of designer benzodiazepines Manchester, Kieran R. Waters, Laura Haider, Shozeb Maskell, Peter D. Forensic Toxicol Short Communication PURPOSE: The number of benzodiazepines appearing as new psychoactive substances (NPS) is continually increasing. Information about the pharmacological parameters of these compounds is required to fully understand their potential effects and harms. One parameter that has yet to be described is the blood-to-plasma ratio. Knowledge of the pharmacodynamics of designer benzodiazepines is also important, and the use of quantitative structure–activity relationship (QSAR) modelling provides a fast and inexpensive method of predicting binding affinity to the GABA(A) receptor. METHODS: In this work, the blood-to-plasma ratios for six designer benzodiazepines (deschloroetizolam, diclazepam, etizolam, meclonazepam, phenazepam, and pyrazolam) were determined. A previously developed QSAR model was used to predict the binding affinity of nine designer benzodiazepines that have recently appeared. RESULTS: Blood-to-plasma values ranged from 0.57 for phenazepam to 1.18 to pyrazolam. Four designer benzodiazepines appearing since 2017 (fluclotizolam, difludiazepam, flualprazolam, and clobromazolam) had predicted binding affinities to the GABA(A) receptor that were greater than previously predicted binding affinities for other designer benzodiazepines. CONCLUSIONS: This work highlights the diverse nature of the designer benzodiazepines and adds to our understanding of their pharmacology. The greater predicted binding affinities are a potential indication of the increasing potency of designer benzodiazepines appearing on the illicit drugs market. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s11419-022-00616-y. Springer Nature Singapore 2022-03-16 2022 /pmc/articles/PMC9715504/ /pubmed/36454409 http://dx.doi.org/10.1007/s11419-022-00616-y Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Short Communication Manchester, Kieran R. Waters, Laura Haider, Shozeb Maskell, Peter D. The blood-to-plasma ratio and predicted GABA(A)-binding affinity of designer benzodiazepines |
title | The blood-to-plasma ratio and predicted GABA(A)-binding affinity of designer benzodiazepines |
title_full | The blood-to-plasma ratio and predicted GABA(A)-binding affinity of designer benzodiazepines |
title_fullStr | The blood-to-plasma ratio and predicted GABA(A)-binding affinity of designer benzodiazepines |
title_full_unstemmed | The blood-to-plasma ratio and predicted GABA(A)-binding affinity of designer benzodiazepines |
title_short | The blood-to-plasma ratio and predicted GABA(A)-binding affinity of designer benzodiazepines |
title_sort | blood-to-plasma ratio and predicted gaba(a)-binding affinity of designer benzodiazepines |
topic | Short Communication |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9715504/ https://www.ncbi.nlm.nih.gov/pubmed/36454409 http://dx.doi.org/10.1007/s11419-022-00616-y |
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