Flumazenil induces seizures and death in mixed cocaine-diazepam intoxications

Robert W. Derlet, Timothy E Albertson

Research output: Contribution to journalArticlepeer-review

16 Scopus citations


Study hypothesis: Administration of the benzodiazepine antagonist flumazenil may unmask seizures in mixed cocainebenzodiazepine intoxication. Design: Male Sprague-Dawley rats received 100 mg/kg cocaine IP alone, 5 mg/kg diazepam alone, or a combination of diazepam and cocaine. Three minutes later, groups were challenged with vehicle or flumazenil 5 or 10 mg/kg IP. Animal behavior, seizures (time to and incidence), death (time to and incidence), and cortical EEG tracings were recorded. Interventions: Administration of flumazenil to animals after they had received a combination dose of cocaine and diazepam. Results: In group 1, animals received cocaine followed by vehicle. This resulted in 100% developing seizures and death. Group 2 received diazepam alone followed by vehicle. Animals became somnolent and none died. Group 3 received diazepam followed by 5 mg/kg flumazenil. Animals became somnolent after diazepam and then active after flumazenil administration. In group 4, a combination of cocaine and diazepam was administered simultaneously. This resulted in no overt or EEG-detectable seizures and a 50% incidence of death. Group 5 received a similar combination of cocaine and diazepam, followed later by 5 mg/kg flumazenil. This resulted in an increased incidence of seizures, 90% (P<.01), and death, 100% (P≤.01), compared with group 4. Group 6 received cocaine and diazepam followed by 10 mg/kg flumazenil. This also resulted in an increased incidence of seizures, 90% (P≤.01), and death, 90% (P≤.05), compared with group 4. Conclusion: Flumazenil can unmask seizures and increase the incidence of death in a model of combined cocaine-diazepam intoxications.

Original languageEnglish (US)
Pages (from-to)494-498
Number of pages5
JournalAnnals of Emergency Medicine
Issue number3
StatePublished - 1994

ASJC Scopus subject areas

  • Emergency Medicine


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