The central nervous system effects of the partial GABA‐Aα2,3‐selective receptor modulator AZD7325 in comparison with lorazepam in healthy males

• DOI: 10.1111/bcp.12413
• Publication Date: 2014-05-07T02:09:19Z
• Authors: Xia Chen; Gabriël Jacobs; Marieke de Kam; Judith Jaeger; Jaakko Lappalainen; Paul Maruff; Mark A. Smith; Alan J. Cross; Adam Cohen; Joop van Gerven
• Keywords: Lorazepam; Pharmacodynamics; Crossover study

AZD7325 is a novel α2,3 -subtype-selective partial GABA-A-receptor modulator. This study investigated the pharmacodynamics of single oral doses 2 mg and 10 on central nervous system (CNS) compared with placebo lorazepam mg.This double-blind, randomized, four way crossover enrolled 16 healthy males administered two validated CNS test batteries to measure drug effects cognitive, neurophysiologic psychomotor function subjective feelings. The pharmacological selectivity was by plotting saccadic peak velocity change from baseline (ΔSPV) against body sway (ΔSway) visual analogue scale for alertness(ΔVASalertness ). analysis has previously been used identify -subtype-selectivity.In contrast robust impairment caused (all P < 0.05 vs. placebo), neither dose induced statistically significant any pharmacodynamic measurements. Lorazepam-induced SPV-reduction linearly related changes in other biomarkers. In contrast, slopes regression lines were flatter AZD7325, particularly Δlog(Sway) -ΔSPV relation (estimate slope, lorazepam, difference [95% confidence interval], value -0.00036 -0.00206, 0.001704 [0.000639, 0.002768], = 0.0018) ΔVASalertness relationship (0.01855 0.08216, -0.06360 [-0.1046, -0.02257], 0.0024). different response patterns VAS 'feeling high' electro-encephalography.The characteristic ΔSPV-relative effect profiles suggest anxio-selectivity -selective GABAA agonism. However, exploration higher may be warranted. paucity most CNS-PD parameters also indicates mitigated side pattern, potentially lower cognitive neurophysiological burden than non-selective benzodiazepines.