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 (alphax beta2/3 gamma2, x= 1-3, 5) expressed in HEK293 cells. Compound 4 displayed affinity only for alpha1 beta2 gamma2 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.
A novel selective GABA-A alpha1 receptor agonist displaying sedative and anxiolytic-like properties in rodents / S. SELLERI; F. BRUNI; C. COSTAGLI; A. COSTANZO; G. GUERRINI; G. CICIANI; P. GRATTERI; F. BESNARD; B. COSTA; C. MARTINI; G. DE SIENA; P. MALMBERG; M. MONTALI; J. FOHLIN. - In: JOURNAL OF MEDICINAL CHEMISTRY. - ISSN 0022-2623. - STAMPA. - 48:(2005), pp. 6756-6760. [10.1021/jm058002n]
A novel selective GABA-A alpha1 receptor agonist displaying sedative and anxiolytic-like properties in rodents.
SELLERI, SILVIA;BRUNI, FABRIZIO;COSTANZO, ANNARELLA;GUERRINI, GABRIELLA;CICIANI, GIOVANNA;GRATTERI, PAOLA;DE SIENA, GAETANO;MALMBERG, PETRA;
2005
Abstract
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 (alphax beta2/3 gamma2, x= 1-3, 5) expressed in HEK293 cells. Compound 4 displayed affinity only for alpha1 beta2 gamma2 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.
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