RESUMO
Early pharmacological studies in animals demonstrated that ABIO-08/01, a new isoxazoline, exerted anxiolytic and anticonvulsant, but also cognition-enhancing properties. Thus, the aim of the present double-blind, placebo-controlled multiple-ascending-dose study was to investigate the effect of the new compound on event-related potentials (ERPs). In a randomized ascending-dose design for phase-1 studies, 16 young healthy male subjects aged 30.2 +/- 5.7 years received three ascending drug doses (10, 20, and 40 mg) and placebo for 7 days, with a washout period of 8 days in between. Auditory ERPs were recorded pre-dose and 2 h post-dose on days 1 (acute effect) and 5 (subacute and absolute superimposed effect). Descriptive statistics with one confirmatory statement on P300 latency demonstrated a significant shortening after acute, subacute, and superimposed administration of 40 mg ABIO-08/01. While ERP amplitudes showed only minor effects, low-resolution brain electromagnetic tomography (LORETA) demonstrated that ABIO-08/01 promotes more efficient information processing by reallocating perceptual and cognitive ERP resources. Thus, our ERP studies confirm early pharmacological findings in animals of a cognition-enhancing effect of ABIO-08/01, which is interesting in the context of the anxiolytic mode of action of the compound as its CNS effects are quite different from those of anxiolytic sedatives, such as benzodiazepines.
