一种新型选择性γ-氨基丁酸A（GABA(A)）α1受体激动剂，在啮齿动物中表现出镇静和抗焦虑样特性。
A novel selective GABA(A) alpha1 receptor agonist displaying sedative and anxiolytic-like properties in rodents.
作者信息
Selleri Silvia, Bruni Fabrizio, Costagli Camilla, Costanzo Annarella, Guerrini Gabriella, Ciciani Giovanna, Gratteri Paola, Besnard François, Costa Barbara, Montali Marina, Martini Claudia, Fohlin Jonna, De Siena Gaetano, Aiello Petra Malmberg
机构信息
Department of Pharmaceutical Sciences, University of Firenze, Via U. Schiff 6, 50019 Sesto Fiorentino, Italy.
出版信息
J Med Chem. 2005 Oct 20;48(21):6756-60. doi: 10.1021/jm058002n.
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.
在我们寻找苯二氮䓬/γ-氨基丁酸A（Bz/GABA(A)）受体亚型选择性配体的过程中，合成了一种新型吡唑并[1,5-a]嘧啶衍生物（4），即唑吡坦的氮杂类似物，并在体外对牛脑匀浆以及在HEK293细胞中表达的重组苯二氮䓬受体（αxβ2/3γ2，x = 1 - 3, 5）进行了评估。化合物4仅对α1β2γ2亚型表现出亲和力（K(i) = 31 nM），并且在一项深入的体内研究中，它在啮齿动物中显示出镇静和抗焦虑样特性，而没有任何失忆和肌松作用。
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