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Updated: Aug 15, 2026

Methods for the Discovery of Novel Compounds Modulating a Gamma-Aminobutyric Acid Receptor Type A Neurotransmission
Published on: August 16, 2018
A novel selective GABA(A) alpha1 receptor agonist displaying sedative and anxiolytic-like properties in rodents
Silvia Selleri1, Fabrizio Bruni, Camilla Costagli
1Department of Pharmaceutical Sciences, University of Firenze, Via U. Schiff 6, 50019 Sesto Fiorentino, Italy. silvia.selleri@unifi.it
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.
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