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PQs are also neutral modulators at the benzodiazepine site. We assessed the influence of PQ compounds from three structural groups (PZ\u2010II\u2010029 and related deuterated analogues DK\u2010I\u201056\u20101, RV\u2010I\u2010029, DK\u2010I\u201060\u20103 and DK\u2010I\u201086\u20101; LAU 463 and related analogues DK\u2010I\u201058\u20101 and DK\u2010II\u201058\u20101; and DK\u2010I\u201087\u20101), alone and in combination with diazepam, on the behaviour of male Sprague\u2013Dawley rats. An excellent behavioural safety profile of all tested PQs was demonstrated in the spontaneous locomotor activity, rotarod, loss of righting reflex and pentylenetetrazol tests. In interaction studies, only PZ\u2010II\u2010029 and its analogues prevented the ataxic effects of the benzodiazepine, as assessed in the rotarod test and during monitoring of rat locomotor activity after awakening from the loss of righting reflex. Published electrophysiological profiles of PQ ligands imply that positive modulation elicited at \u03b16\u2010GABA<jats:sub>A<\/jats:sub> receptors that contain the \u03b32 and \u03b4 subunit, rather than their neutral modulatory action at the benzodiazepine site, may prevent the ataxic action of diazepam. Thus, PZ\u2010II\u2010029 and its deuterated analogues are not prone to untoward interactions with benzodiazepines and may indeed completely abolish their ataxic action, seen at therapeutic, and especially toxic concentrations.<\/jats:p>","DOI":"10.1111\/bcpt.13801","type":"journal-article","created":{"date-parts":[[2022,10,1]],"date-time":"2022-10-01T02:10:02Z","timestamp":1664590202000},"page":"514-524","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Behavioural interaction of pyrazoloquinolinone positive allosteric modulators at \u03b16GABA<sub>A<\/sub> receptors and diazepam in rats: Anti\u2010diazepam\u2010induced ataxia action as a structure\u2010dependent feature"],"prefix":"10.1111","volume":"131","author":[{"given":"Branka","family":"Divovi\u0107 Matovi\u0107","sequence":"first","affiliation":[{"name":"Department of Pharmacology University of Belgrade \u2013 Faculty of Pharmacy  Belgrade Serbia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dan","family":"Knutson","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry, Milwaukee Institute for Drug Discovery University of Wisconsin\u2010Milwaukee  Milwaukee Wisconsin USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jelena","family":"Mitrovi\u0107","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Technology and Cosmetology University of Belgrade \u2013 Faculty of Pharmacy  Belgrade Serbia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vladimir","family":"Stevanovi\u0107","sequence":"additional","affiliation":[{"name":"Department of Pharmacology University of Belgrade \u2013 Faculty of Pharmacy  Belgrade Serbia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Boban","family":"Stanojevi\u0107","sequence":"additional","affiliation":[{"name":"Laboratory for Radiobiology and Molecular Genetics, Vin\u010da Institute of Nuclear Sciences, National Institute of th\u0435 Republic of Serbia University of Belgrade  Belgrade Serbia"},{"name":"Comprehensive Cancer Centre, Faculty of Life Sciences &amp; 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