NS11821 is a partial GABAA agonist with relatively dominant α2,3 and α5 subtype efficacy but negligible α1 agonism. This first-in-human study was performed in healthy male subjects using a single-dose, parallel, double blind, placebo-controlled, randomized, dose-escalation study design. In total six cohorts (N=48) were enrolled. The eight subjects of each cohort received NS11821 (10 mg, 30 mg, 75 mg, 150 mg, 300 mg or 600 mg) or placebo in a 6:2 ratio. At low dose levels, NS11821 had a relatively low exposure and a more-than-proportional increase of the area under the curve and maximum plasma concentrations, probably due to poor solubility. Saccadic peak velocity decreased in a dose-related manner while limited impairments were seen on body sway and the visual analogue scale for alertness. The most common adverse events were somnolence and dizziness, which were more prominent with the higher doses. Although no positive control was used in this study, the results were compared post hoc with a Centre for Human Drug Research dataset for lorazepam 2 mg. The maximum saccadic peak velocity effects seemed comparable to the typical effects of lorazepam, whereas the other central nervous system effects were smaller. These results support the pharmacological selectivity of NS11821 and show that pharmacodynamic effective doses of NS11821 were safe and well tolerated in healthy subjects.