title: Resuscitative effect of a gamma-aminobutyric acid B receptor antagonist on gamma-hydroxybutyric acid mortality in mice.
abstract: OBJECTIVE
  In the present study, a number of compounds were tested to evaluate their efficacy in exerting a protective effect on gamma-hydroxybutyric acid (GHB)-induced mortality in mice. The drugs investigated were the gamma-aminobutyric acid B (GABA B ) receptor antagonist SCH 50911, the GABA A receptor antagonist bicuculline, the benzodiazepine receptor antagonist flumazenil, the putative GHB receptor antagonist NCS-382, the opioid receptor antagonist naltrexone, and the amino acid and possible neuromodulator, taurine.
  
  
  METHODS
  All mice were initially treated with a lethal dose of GHB (7 g/kg, administered intragastrically). Once mice had displayed clear signs of GHB intoxication, animals from each group were treated acutely with either SCH 50911 (vehicle; 75, 150, and 300 mg/kg, administered intraperitoneally), bicuculline (vehicle; 2, 4, 6, and 8 mg/kg, administered intraperitoneally), flumazenil (vehicle; 1, 3, and 10 mg/kg, administered intraperitoneally), NCS-382 (vehicle; 50 and 200 mg/kg, administered intraperitoneally), naltrexone (vehicle; 3 and 10 mg/kg, administered intraperitoneally), or taurine (vehicle; 250 and 750 mg/kg, administered intraperitoneally). The various doses of each single drug were administered to 10 mice, randomly allocated throughout the experimental groups. Mortality was recorded every hour for the first 9 hours and subsequently 12, 18, and 24 hours after GHB injection.
  
  
  RESULTS
  In each experiment, all vehicle-treated mice died within 24 hours of GHB injection. Doses of 150 and 300 mg/kg SCH 50911 produced a marked protection on GHB-induced mortality, evidenced by the death of only 0 of 10 and 2 of 10 mice in the 150- and 300-mg/kg SCH 50911 groups, respectively. In contrast, at all doses tested, bicuculline, flumazenil, NCS-382, naltrexone, and taurine were not observed to exert any protective effect on GHB-induced mortality (9 to 10/10 mice died in each treatment group).
  
  
  CONCLUSIONS
  These results suggest an involvement of the GABA B receptor, at least in rodents, in the mediation of the lethal effects of GHB.
authors.affiliation: Bernard B. Brodie Department of Neuroscience, School of Medicine, University of Cagliari, and CNR Institute of Neuroscience, Section of Cagliari, Italy. macarai@unica.it
authors.forename: Mauro A M
authors.initials: MA
authors.lastname: Carai
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Colombo
authors.forename: Gian Luigi
authors.initials: GL
authors.lastname: Gessa
mesh_terms: D000818:Animals; D001567:Benzocycloheptenes / Q000494:pharmacology; D001640:Bicuculline / Q000494:pharmacology; D062787:Drug Overdose / Q000188:drug therapy; D005442:Flumazenil / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology*; D008297:Male; D051379:Mice; D009025:Morpholines / Q000494:pharmacology; D009271:Naltrexone / Q000494:pharmacology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D018377:Neurotransmitter Agents / Q000494:pharmacology; D015996:Survival Rate; D013654:Taurine / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000633:toxicity*
chemical_list: C095804:(+)-(S)-5,5-dimethylmorpholinyl-2-acetic acid; D001567:Benzocycloheptenes; D018756:GABA Antagonists; D009025:Morpholines; D018696:Neuroprotective Agents; D018377:Neurotransmitter Agents; C066471:NCS 382; D013654:Taurine; D005442:Flumazenil; D005680:gamma-Aminobutyric Acid; D009271:Naltrexone; D001640:Bicuculline