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  • A novel selective GABA(A) alpha1 receptor agonist displaying sedative and anxiolytic-like properties in rodents.

A novel selective GABA(A) alpha1 receptor agonist displaying sedative and anxiolytic-like properties in rodents.

Journal of medicinal chemistry (2005-10-14)
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
PMID16220991
ABSTRACT

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 (alphaxbeta2/3gamma2, x = 1-3, 5) expressed in HEK293 cells. Compound 4 displayed affinity only for alpha1beta2gamma2 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.