Protection by the GABAB receptor antagonist, SCH 50911, of gamma-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 acidB (GABAB) receptor antagonists. The present study investigated whether the protective effect of GABAB 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.
Carai
Mauro A M
MA
"Bernard B. Brodie" Department of Neuroscience, University of Cagliari, Viale Diaz 182, I-09126 Cagliari (CA), Italy. mcarai@unica.it
Colombo
Giancarlo
G
Gessa
Gian Luigi
GL
D018686:Anesthetics, Intravenous / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D058788:GABA-B Receptor Antagonists; D007928:Lethal Dose 50; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D009025:Morpholines / Q000494:pharmacology*; D012978:Sodium Oxybate / Q000037:antagonists & inhibitors* / Q000633:toxicity*
C095804:(+)-(S)-5,5-dimethylmorpholinyl-2-acetic acid; D018686:Anesthetics, Intravenous; D018691:Excitatory Amino Acid Antagonists; D058788:GABA-B Receptor Antagonists; D009025:Morpholines; D012978:Sodium Oxybate