title: Double-blind, placebo-controlled, multiple-ascending-dose study on the effects of ABIO-08/01, a novel anxiolytic drug, on perception and cognition, utilizing event-related potential mapping and low-resolution brain electromagnetic tomography.
abstract: 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.
authors.affiliation: Department of Psychiatry and Psychotherapy, Medical University of Vienna, Vienna, Austria. peter.anderer@meduniwien.ac.at
authors.forename: Peter
authors.initials: P
authors.lastname: Anderer
authors.forename: Bernd
authors.initials: B
authors.lastname: Saletu
authors.forename: Michael
authors.initials: M
authors.lastname: Wolzt
authors.forename: Svetlana
authors.initials: S
authors.lastname: Culic
authors.forename: Alessandro
authors.initials: A
authors.lastname: Assandri
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Nannipieri
authors.forename: Sergio
authors.initials: S
authors.lastname: Rosini
authors.forename: Gerda M
authors.initials: GM
authors.lastname: Saletu-Zyhlarz
mesh_terms: D000328:Adult; D014151:Anti-Anxiety Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D000927:Anticonvulsants / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D001931:Brain Mapping; D003071:Cognition / Q000187:drug effects*; D018592:Cross-Over Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004569:Electroencephalography / Q000379:methods; D005072:Evoked Potentials, Auditory / Q000187:drug effects*; D006801:Humans; D007555:Isoxazoles / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology*; D008297:Male; D010465:Perception / Q000187:drug effects*; D014054:Tomography / Q000379:methods
chemical_list: C529993:ABIO 0801; D014151:Anti-Anxiety Agents; D000927:Anticonvulsants; D007555:Isoxazoles