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Sedative-motor effects of benzodiazepines are thought to involve \u03b11GABA\n                      <jats:sub>A<\/jats:sub>\n                      and \u03b13GABA\n                      <jats:sub>A<\/jats:sub>\n                      subtypes.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Aims:<\/jats:title>\n                    <jats:p>\n                      We evaluated observable measures of sedative-motor effects and species-typical behaviors in monkeys following acute administration of novel GABAkines (positive allosteric modulators of GABA\n                      <jats:sub>A<\/jats:sub>\n                      receptors), with varying degrees of selective efficacy at different GABA\n                      <jats:sub>A<\/jats:sub>\n                      receptor subtypes. We predicted that the induction of sedative-motor effects would depend on the degree of \u03b11GABA\n                      <jats:sub>A<\/jats:sub>\n                      and \u03b13GABA\n                      <jats:sub>A<\/jats:sub>\n                      efficacy.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>\n                      Adult female rhesus monkeys (\n                      <jats:italic>N<\/jats:italic>\n                      \u2009=\u20094) were implanted with chronic indwelling i.v. catheters. Quantitative behavioral observation was conducted by trained observers following administration of multiple doses of the conventional benzodiazepine alprazolam and the GABAkines MP-III-80 (preferential efficacy at \u03b12\/\u03b13\/\u03b15GABA\n                      <jats:sub>A<\/jats:sub>\n                      subtypes), KRM-II-81, MP-III-24 (both with preferential efficacy for \u03b12\/\u03b13GABA\n                      <jats:sub>A<\/jats:sub>\n                      subtypes), and MP-III-22 (preferential potency and efficacy for \u03b15GABA\n                      <jats:sub>A<\/jats:sub>\n                      subtypes).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      As with alprazolam, all GABAkines induced significant levels of mild sedation (\u201crest\/sleep posture\u201d). Deep sedation was observed with alprazolam, MP-III-80, and MP-III-22; motoric effects (observable ataxia) were obtained with alprazolam, KRM-II-81, and MP-III-22 only. Surprisingly, the order of potency for rest\/sleep posture was significantly associated only with potency at \u03b15GABA\n                      <jats:sub>A<\/jats:sub>\n                      subtypes.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>\n                      GABAkines with preferential efficacy at \u03b12\/\u03b13GABA\n                      <jats:sub>A<\/jats:sub>\n                      and\/or \u03b15GABA\n                      <jats:sub>A<\/jats:sub>\n                      subtypes engendered sedative-motor effects in monkeys, although only compounds with \u03b15GABA\n                      <jats:sub>A<\/jats:sub>\n                      activity engendered deep sedation. Moreover, the significant relationship between potency obtained with in vitro electrophysiology data and the rest\/sleep posture measure suggests a role for the \u03b15GABA\n                      <jats:sub>A<\/jats:sub>\n                      subtype in this milder form of sedation.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/02698811241286760","type":"journal-article","created":{"date-parts":[[2024,10,10]],"date-time":"2024-10-10T08:40:26Z","timestamp":1728549626000},"page":"1157-1169","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":4,"title":["Evaluation of the sedative-motor effects of novel GABAkine imidazodiazepines using quantitative observation techniques in rhesus monkeys"],"prefix":"10.1177","volume":"38","author":[{"given":"Dishary","family":"Sharmin","sequence":"first","affiliation":[{"name":"Department of Chemistry and Biochemistry, University of Wisconsin-Milwaukee, Milwaukee, WI, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"R\u00fcedi-Bettschen","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Human Behavior, Center for Innovation and Discovery in Addictions, University of Mississippi Medical Center, Jackson, MS, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"La\u00eds F","family":"Berro","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Human Behavior, Center for Innovation and Discovery in Addictions, University of Mississippi Medical Center, Jackson, MS, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jemma E","family":"Cook","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Human Behavior, Center for Innovation and Discovery in Addictions, University of Mississippi Medical Center, Jackson, MS, USA"},{"name":"Department of Social Sciences and Public Administration, West Virginia University Institute of Technology, Beckley, WV, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaren A","family":"Reeves-Darby","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Human Behavior, Center for Innovation and Discovery in Addictions, University of Mississippi Medical Center, Jackson, MS, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9133-0811","authenticated-orcid":false,"given":"Tanya","family":"Pareek","sequence":"additional","affiliation":[{"name":"Department of Psychiatry and Human Behavior, Center for Innovation and Discovery in Addictions, University of Mississippi Medical Center, Jackson, MS, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Md Yeunus","family":"Mian","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry, University of Wisconsin-Milwaukee, Milwaukee, WI, 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