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Novel chemically similar compounds, designer BZDs (DBZDs), have emerged on the recreational market with little information available on their pharmacodynamic effects. An in vitro \u03b1\n                    <jats:sub>1<\/jats:sub>\n                    \u03b2\n                    <jats:sub>2<\/jats:sub>\n                    \u03b3\n                    <jats:sub>2<\/jats:sub>\n                    GABA\n                    <jats:sub>A<\/jats:sub>\n                    assay was used to determine the activity and explore structure-activity relationships of 42 DBZDs plus 11 prescription BZDs. Their interaction with the BZD \u03b1\n                    <jats:sup>+<\/jats:sup>\n                    \/\u03b3\n                    <jats:sub>2<\/jats:sub>\n                    <jats:sup>\u2013<\/jats:sup>\n                    interface was explored using the BZD antagonist flumazenil. Most of the D\/BZDs were positive allosteric modulators, but 4\u2019-chlorodiazepam and 4\u2019-fluorodiazepam were negative allosteric modulators, although the activity was not antagonized by flumazenil. All metabolites tested were active. This data informs the interpretation of intoxications, harm reduction measures, and drugs legislation for DBZDs; demonstrates the importance of testing new drugs as they emerge on the recreational market; and offers insights into how BZD chemical modifications alter GABA\n                    <jats:sub>A<\/jats:sub>\n                    pharmacodynamics.\n                  <\/jats:p>","DOI":"10.1038\/s42004-026-02001-x","type":"journal-article","created":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T16:06:05Z","timestamp":1775577965000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["In vitro \u03b3-aminobutyric acid A (GABAA) receptor activity and binding interactions at the \u03b1+\/\u03b32\u2013 interface of 53 prescription and designer benzodiazepines"],"prefix":"10.1038","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2322-0367","authenticated-orcid":false,"given":"Caitlyn","family":"Norman","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8493-0114","authenticated-orcid":false,"given":"Sara I.","family":"Liin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amaia","family":"Jauregi-Miguel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nina E.","family":"Ottosson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8015-5728","authenticated-orcid":false,"given":"Henrik","family":"Gr\u00e9en","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2026,4,7]]},"reference":[{"key":"2001_CR1","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.drugpo.2021.103512","volume":"100","author":"A McAuley","year":"2022","unstructured":"McAuley, A., Matheson, C. & Robertson, J. 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