Protection by the GABAB receptor antagonist, SCH 50911, of γ-hydroxybutyric acid-induced mortality in mice

Different effects of moderate to high doses of gamma-hydroxybutyric acid, including sedation/hypnosis, have been found to be blocked by gamma-aminobutyric acid(B) (GABA(B)) receptor antagonists. The present study investigated whether the protective effect of GABA(B) receptor antagonists extends also to gamma-hydroxybutyric acid-induced mortality. To this aim, the present study investigated the effect of the GABAB receptor antagonist, (2S)(+)-5,5-dimethyl-2-morpholineacetic acid (SCH 50911; 100 mg/kg, ip), on mortality induced by gamma-hydroxybutyric acid (1-6 g/kg, ip) in DBA mice. Pretreatment with SCH 50911 resulted in a significant shift to the right of the dose-response curve of gamma-hydroxybutyric acid-induced mortality. Accordingly, the LD50 in SCH 50911-pretreated mice was significantly higher than that obtained in water-pretreated mice. The results of the present study support the hypothesis that (a) the GABAB receptor is a relevant site of action of,gamma-hydroxybutyric acid, and (b) GABAB receptor antagonists may constitute potentially effective therapeutic interventions for gamma-hydroxybutyric acid intoxication. (C) 2004 Elsevier B.V. All rights reserved.