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We thus hypothesized that enhancing their activity may help in neuropathic syndromes originating from the trigeminal system. Here, we performed a detailed electrophysiological and pharmacokinetic analysis of two recently developed deuterated structurally similar pyrazoloquinolinone compounds. DK\u2010I\u201056\u20101 at concentrations below 1\u00a0\u00b5M enhanced \u03b3\u2010aminobutyric acid (GABA) currents at recombinant rat \u03b16\u03b23\u03b32, \u03b16\u03b23\u03b4 and \u03b16\u03b23 receptors, whereas it was inactive at most GABA<jats:sub>A<\/jats:sub> receptor subtypes containing other \u03b1 subunits. DK\u2010I\u201087\u20101 at concentrations below 1\u00a0\u00b5M was inactive at \u03b16\u2010containing receptors and only weakly modulated other GABA<jats:sub>A<\/jats:sub> receptors investigated. Both plasma and brain tissue kinetics of DK\u2010I\u201056\u20101 were relatively slow, with half\u2010lives of 6 and 13\u00a0hr, respectively, enabling the persistence of estimated free brain concentrations in the range 10\u2013300\u00a0nM throughout a 24\u2010hr period. Results obtained in two protocols of chronic constriction injury of the infraorbital nerve in rats dosed intraperitoneally with DK\u2010I\u201056\u20101 during 14\u00a0days after surgery or with DK\u2010I\u201056\u20101 or DK\u2010I\u201087\u20101 during 14\u00a0days after trigeminal neuropathy were already established, demonstrated that DK\u2010I\u201056\u20101 but not DK\u2010I\u201087\u20101 significantly reduced the hypersensitivity response to von Frey filaments.<\/jats:p><\/jats:sec><jats:sec><jats:title>Significance<\/jats:title><jats:p>Neuropathic pain induced by trigeminal nerve damage is poorly controlled by current treatments. DK\u2010I\u201056\u20101 that positively modulates \u03b16 GABA<jats:sub>A<\/jats:sub> receptors is appropriate for repeated administration and thus may represent a novel treatment option against the development and maintenance of trigeminal neuropathic pain.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ejp.1365","type":"journal-article","created":{"date-parts":[[2019,1,11]],"date-time":"2019-01-11T17:23:32Z","timestamp":1547227412000},"page":"973-984","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":34,"title":["Trigeminal neuropathic pain development and maintenance in rats are suppressed by a positive modulator of \u03b16 GABA<sub>A<\/sub> receptors"],"prefix":"10.1002","volume":"23","author":[{"given":"Dina","family":"Vasovi\u0107","sequence":"first","affiliation":[{"name":"School of Dental Medicine University of Belgrade  Belgrade 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