An investigation of flumazenil to antagonize gamma-hydroxybutyrate intoxication in a murine model.
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.
Lee
David C
DC
Department of Emergency Medicine, Drexel University/Medical College of Pennsylvania, PA, USA. dlee@nshs.edu
Satz
Wayne A
WA
Dougherty
Timothy
T
Greene
Tucker
T
D000818:Animals; D000931:Antidotes / Q000494:pharmacology* / Q000627:therapeutic use; D001522:Behavior, Animal / Q000187:drug effects*; D004195:Disease Models, Animal; D005442:Flumazenil / Q000494:pharmacology* / Q000627:therapeutic use; D051379:Mice; D010865:Pilot Projects; D011041:Poisoning / Q000188:drug therapy; D011187:Posture; D012018:Reflex / Q000187:drug effects; D012107:Research Design; D012978:Sodium Oxybate; D013997:Time Factors
D000931:Antidotes; D005442:Flumazenil; D012978:Sodium Oxybate