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

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journal contribution
posted on 20.10.2005, 00:00 by Silvia Selleri, Fabrizio Bruni, Camilla Costagli, Annarella Costanzo, Gabriella Guerrini, Giovanna Ciciani, Paola Gratteri, François Besnard, Barbara Costa, Marina Montali, Claudia Martini, Jonna Fohlin, Gaetano De Siena, Petra Malmberg Aiello
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.