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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\u2013activity relationship (QSAR) modelling provides a fast and inexpensive method of predicting binding affinity to the GABA<jats:sub>A<\/jats:sub> receptor.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>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.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>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<jats:sub>A<\/jats:sub> receptor that were greater than previously predicted binding affinities for other designer benzodiazepines.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>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.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1007\/s11419-022-00616-y","type":"journal-article","created":{"date-parts":[[2022,3,16]],"date-time":"2022-03-16T10:05:42Z","timestamp":1647425142000},"page":"349-356","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["The blood-to-plasma ratio and predicted GABAA-binding affinity of designer benzodiazepines"],"prefix":"10.1007","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0893-6255","authenticated-orcid":false,"given":"Kieran R.","family":"Manchester","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Waters","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shozeb","family":"Haider","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter D.","family":"Maskell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,3,16]]},"reference":[{"key":"616_CR1","doi-asserted-by":"publisher","first-page":"554","DOI":"10.1016\/j.janxdis.2011.01.002","volume":"25","author":"F L\u00f3pez-Munoz","year":"2011","unstructured":"L\u00f3pez-Munoz F, \u00c1lamo C, Garc\u00eda-Garc\u00eda P (2011) The discovery of chlordiazepoxide and the clinical introduction of benzodiazepines: Half a century of anxiolytic drugs. 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