Abstract
Objective
Prior animal studies have suggested that flumazenil may blunt GHB’s sedative-hypnotic affects. We hypothesized that flumazenil would decrease the affects of GHB in a murine model of intoxication.
Methods
We performed a controlled, pilot experiment using 32 mice divided into 3 groups. All mice received intraperitoneal injections of GHB (1.5 g/kg). Group I received sham injections at time 0, and then GHB at 5 minutes. Group II received flumazenil (0.3 mg/kg) at time 0, and then GHB at 5 minutes. Group III received sham injection at time 0, then GHB at 5 minutes, and then 4 escalating flumazenil doses administered at 3-minute intervals (0.003 to 1 mg/kg). We measured certain functions: time to loss/recovery of righting reflexes (RR), time to sprawl/recovery of sprawl (postural tone [PT]), and death.
Results
There were statistically significant delays in the loss of PT and shortened recovery time to RR in pre-treated mice (group II) versus controls (group I). There were no differences in group III versus group I for any outcome parameters.
Conclusions
In this model, pre-dosing flumazenil prior to GHB administration delayed clinical intoxication.
Keywords: gamma-hydroxy butyrate, flumazenil, poisoning, mice
Full Text
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Refences
- 1.Chin RL, Sporer KA, Cullison B, Dyer JE, Wu TD. Clinical course of gamma-hydroxybutyrate overdose [see comments] Ann Emerg Med. 1998;31:716–22. doi: 10.1016/S0196-0644(98)70230-6. [DOI] [PubMed] [Google Scholar]
- 2.Gerra G, Caccavari R, Fontanesi B, Marcato A, Fertonani AG, Maestri D, et al. Flumazenil effects on growth hormone response to gamma hydroxybutyric acid. Int Clin Psychopharmacol. 1994;9:211–5. doi: 10.1097/00004850-199409000-00011. [DOI] [PubMed] [Google Scholar]
- 3.Mason PE, Kerns WP. Gamma hydroxybutyric acid (GHB) intoxication. Acad Emerg Med. 2002;9:730–9. doi: 10.1111/j.1553-2712.2002.tb02154.x. [DOI] [PubMed] [Google Scholar]
- 4.Carai MA, Colombo G, Gessa GL. Resuscitative effect of a gamma aminobutyric acid B receptor antagonist on gamma-hydroxybutyric acid mortality in mice. Ann Emerg Med. 2005;45:614–9. doi: 10.1016/j.annemergmed.2004.12.013. [DOI] [PubMed] [Google Scholar]
- 5.Schmidt-Mutter C, Pain L, Sandner G, Gobaille S, Maitre M. The anxiolytic effect of gamma-hydroxybutyrate in the elevated plus maze is reversed by the benzodiazepine receptor antagonist, flumazenil. Eur J Pharmacol. 1998;342:21–7. doi: 10.1016/S0014-2999(97)01503-3. [DOI] [PubMed] [Google Scholar]
- 6.McMahon LR, Coop A, France CP, Winger G, Woolverton WL. Evaluation of the reinforcing and discriminative stimulus effects of 1,4 butanediol and gamma-butyrolactone in rhesus monkeys. Eur J Pharmacol. 2003;466:113–20. doi: 10.1016/S0014-2999(03)01486-9. [DOI] [PubMed] [Google Scholar]
- 7.Gerra G, Caccavari R, Fontanesi B, Fertonani AG, Maestri D, Avanzini P, et al. Naloxone and metergoline effects on growth hormone response to gamma-hydroxybutyric acid. Int Clin Psychopharmacol. 1995;10:245–50. doi: 10.1097/00004850-199511000-00006. [DOI] [PubMed] [Google Scholar]
- 8.Adachi YU, Watanabe K, Higuchi H, Satoh T. Flumazenil reduces the hypnotic dose of propofol in male patients under spinal anesthesia. J Anesth. 2002;16:9–12. doi: 10.1007/s540-002-8087-2. [DOI] [PubMed] [Google Scholar]
- 9.Adachi YU, Watanabe K, Higuchi H, Satoh T. High-dose flumazenil potentiates the hypnotic activity of propofol, but not that of thiopental, in ddY mice. Acta Anaesthesiol Scand. 2001;45:848–52. doi: 10.1034/j.1399-6576.2001.045007848.x. [DOI] [PubMed] [Google Scholar]