NS11394 is the novel subtype-selective GABAA receptor-positive modulator which possesses a functional efficacy selectivity profile of alpha5 > alpha3 > alpha2 > alpha1 at GABAA alpha subunit-containing receptors. Compared with other subtype-selective ligands, NS11394 is unique in having superior efficacy at GABAA-alpha3 receptors while maintaining low efficacy at GABAA- alpha1 receptors. NS11394 has an excellent pharmacokinetic profile, which correlates with pharmacodynamics endpoints (CNS receptor occupancy), yielding a high level of confidence in deriving in vivo conclusions anchored to an in vitro selectivity profile and allowing for translation to higher species. Specifically, we show that NS11394 is potent and highly effective in rodent anxiety models. The anxiolytic efficacy of NS11394 is most probably mediated through its high efficacy at GABAA-alpha3 receptors, although a contributory role of GABAA-alpha2 receptors cannot be excluded.