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dc.contributor.authorManchester, Kieran R.
dc.contributor.authorWaters, L.
dc.contributor.authorHaider, S.
dc.contributor.authorMaskell, P.D.
dc.date.accessioned2022-03-16T12:16:23Z
dc.date.accessioned2022-03-17T15:55:49Z
dc.date.available2022-03-16T12:16:23Z
dc.date.available2022-03-17T15:55:49Z
dc.date.issued2022-03
dc.identifier.citationManchester KR, Waters L, Haider S et al (2022) The blood-to-plasma ratio and predicted GABAA-binding affinity of designer benzodiazepines. Forensic Toxicology. 40: 349-356.en_US
dc.identifier.urihttp://hdl.handle.net/10454/18785
dc.descriptionYesen_US
dc.description.abstractPurpose: 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 GABAA 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 GABAA 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.en_US
dc.description.sponsorshipEngineering and Physical Sciences Research Council.en_US
dc.language.isoenen_US
dc.relation.isreferencedbyhttps://doi.org/10.1007/s11419-022-00616-yen_US
dc.rights© The Author(s) 2022. Open Access This 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/.en_US
dc.subjectQSARen_US
dc.subjectDesigner benzodiazepinesen_US
dc.subjectNew psychoactive substancesen_US
dc.subjectBlood-to-plasma ratioen_US
dc.subjectGABAA receptoren_US
dc.subjectResearch Development Fund Publication Prize Award
dc.titleThe blood-to-plasma ratio and predicted GABAA-binding affinity of designer benzodiazepinesen_US
dc.status.refereedYesen_US
dc.date.Accepted2022-02-16
dc.date.application2022-03-16
dc.typeArticleen_US
dc.type.versionPublished versionen_US
dc.description.publicnotesResearch Development Fund Publication Prize Award winner, Feb 2022.
dc.rights.licenseCC-BYen_US
dc.date.updated2022-03-16T12:16:25Z
refterms.dateFOA2022-03-17T15:56:35Z
dc.openaccess.statusopenAccessen_US


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