A Novel Selective GABAA α1 Receptor Agonist Displaying Sedative and Anxiolytic-like Properties in Rodents

In our pursuit to identify selective ligands for Bz/GABAA receptor subtypes, a novel pyrazolo[1,5-a]pyrimidine derivative (4), the azaisostere of zolpidem, was synthesized and evaluated in vitro on bovine brain homogenate and on recombinant benzodiazepine receptors (αxβ2/3γ2, x = 1−3, 5) expressed in HEK293 cells. Compound 4 displayed affinity only for α1β2γ2 subtype (Ki = 31 nM), and in an in-depth, in vivo study it revealed sedative and anxiolytic-like properties without any amnesic and myorelaxant effects in rodents.