A novel selective GABAA α1 receptor agonist displaying sedative and anxiolytic-like properties in rodents

In our pursuit to identify selective ligands for Bz/GABA(A) 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 (alpha x beta 2/3 gamma 2, x = 1-3, 5) expressed in HEK293 cells. Compound 4 displayed affinity only for alpha 1 beta 2 gamma 2 subtype (K-i = 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.