Antipsychotic effects of bretazenil, a partial benzodiazepine agonist in acute schizophrenia--a study group report.

The results of an open tolerability and exploratory efficacy study of bretazenil, a partial benzodiazepine-receptor agonist in hospitalized schizophrenic patients with an acute psychotic episode (DSM-III-R criteria), are presented. The duration of the study was 6 weeks, with a mandatory titration (ascending doses of 3-18 mg/day) period of 14 days. The assessment criteria for tolerability were the frequency of adverse events (including EPS), vital signs and laboratory tests.

Benzodiazepines and GABA hypothesis of schizophrenia.

Clinical and experimental studies pertinent for demonstrating the antipsychotic potential of benzodiazepines (BDZ) and the involvement of γ-aminobutyric acid (GABA) in the origin of schizophrenia are reviewed. It is shown that, due to severe methodological problems and pitfalls, placebo-controlled, double-blind studies do not permit unequivocal conclusions on the efficacy of BDZs, but neither do they completely disprove it. Furthermore, at first glance, confusing and controversial findings in animal models indicate a bi-directionality of effects of full BDZ agonists on dopamine-mediated functions, which may perhaps be explained by (i) anatomical and functional organization of the GABA-dopamine system in the nigro-striatal and ventro tegmental area, and (ii) the regional non-selectivity of action of these drugs.