jm058002n_si_001.pdf (316.12 kB)
A Novel Selective GABAA α1 Receptor Agonist Displaying Sedative and Anxiolytic-like Properties in Rodents
journal contribution
posted on 2005-10-20, 00:00 authored 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 AielloIn 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.
