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The antihyperalgesic effects of<jats:styled-content style=\"fixed-case\">GABA<jats:sub>A<\/jats:sub><\/jats:styled-content>agonists are mediated by<jats:styled-content style=\"fixed-case\">GABA<jats:sub>A<\/jats:sub><\/jats:styled-content>receptors containing \u03b12 subunits, whereas sedation is linked to \u03b11 subunit\u2010containing receptors. \u03b12 and \u03b13 selective<jats:styled-content style=\"fixed-case\">GABA<jats:sub>A<\/jats:sub><\/jats:styled-content>receptor modulators have been tested in animals but are not yet available for use in human beings. Clobazam is a 1,5\u2010<jats:styled-content style=\"fixed-case\">BZD<\/jats:styled-content>, which exhibits less cognitive side effects than other benzodiazepines. Here, we studied its antihyperalgesic effects in a mouse model of neuropathic pain. Clobazam showed a dose\u2010dependent antihyperalgesic effect in the chronic constriction injury (<jats:styled-content style=\"fixed-case\">CCI<\/jats:styled-content>) model of neuropathic pain, peaking at 1\u00a0hr after administration and lasting for 4\u00a0hr with no relevant sedation at a dose of 3\u00a0mg\/kg. At higher doses, the antihyperalgesic effect was stronger, but sedation became significant. The blood and brain kinetics of clobazam were linear over the range of doses tested with a short half\u2010life of the parent compound and a ready penetration of the blood\u2013brain barrier. Clobazam blood concentrations decreased rapidly, falling below the limit of detection at 120\u00a0min. after drug application. Its main metabolite,<jats:italic>N<\/jats:italic>\u2010desmethyl\u2010clobazam, showed more delayed and prolonged pharmacokinetics, partly explaining why antihyperalgesia persisted when clobazam was no longer detectable in the blood. Considering its therapeutic margin and its pharmacokinetic properties, clobazam would be a valuable compound to assess the role of the<jats:styled-content style=\"fixed-case\">GABA<\/jats:styled-content>ergic pathway in pain transmission in human beings.<\/jats:p>","DOI":"10.1111\/bcpt.12017","type":"journal-article","created":{"date-parts":[[2013,4,22]],"date-time":"2013-04-22T13:02:12Z","timestamp":1366635732000},"page":"192-197","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Antihyperalgesic Effect of the<scp>GABA<sub>A<\/sub><\/scp>Ligand Clobazam in a Neuropathic Pain Model in Mice: A Pharmacokinetic\u2013Pharmacodynamic Study"],"prefix":"10.1111","volume":"112","author":[{"given":"Marie","family":"Besson","sequence":"first","affiliation":[{"name":"Multidisciplinary Pain Center Clinical Pharmacology and Toxicology Geneva University Hospitals Geneva Switzerland"},{"name":"Clinical Pharmacology and Toxicology Geneva University Hospitals Geneva Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Youssef","family":"Daali","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology and Toxicology Geneva University Hospitals Geneva Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessandra","family":"Di Lio","sequence":"additional","affiliation":[{"name":"Institute of Pharmacology and Toxicology University of Zurich Zurich Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierre","family":"Dayer","sequence":"additional","affiliation":[{"name":"Multidisciplinary Pain Center Clinical Pharmacology and Toxicology Geneva University Hospitals Geneva Switzerland"},{"name":"Clinical Pharmacology and Toxicology Geneva University Hospitals Geneva Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanns Ulrich","family":"Zeilhofer","sequence":"additional","affiliation":[{"name":"Institute of Pharmacology and Toxicology University of Zurich Zurich Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jules","family":"Desmeules","sequence":"additional","affiliation":[{"name":"Multidisciplinary Pain Center Clinical Pharmacology and Toxicology Geneva University Hospitals Geneva Switzerland"},{"name":"Clinical Pharmacology and Toxicology Geneva University Hospitals Geneva Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2012,11,14]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-005-5107-2"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2007.07.009"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pain.2008.10.015"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(96)09024-1"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1526-4637.2000.00044.x"},{"key":"e_1_2_6_7_1","first-page":"179","article-title":"Administration of clonazepam in the treatment of TMD and associated myofascial pain: a double\u2010blind pilot study","volume":"5","author":"Harkins S","year":"1991","journal-title":"J Craniomandib Disord"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpainsymman.2003.09.005"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pain.2003.12.002"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tips.2009.06.004"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tips.2009.05.007"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00109-009-0454-3"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2007.08.008"},{"key":"e_1_2_6_14_1","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1016\/S0031-6997(24)01363-2","article-title":"International Union of Pharmacology. 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