The clinical efficacy of different doses of the specific benzodiazepine 
antagonist flumazenil was studied in a total of 72 patients with benzodiazepine 
or ethanol overdose. In a randomized double-blind study, 18 patients (group 1) 
and eight patients (group 2) with suspected benzodiazepine overdose received 5 
mg (group 1) or 1 mg (group 2) flumazenil or placebo, respectively. The stage of 
coma, heart rate, blood pressure and respiratory rate were monitored within the 
following 15 min. If no change in the stage of coma was observed, 5 mg (group 1) 
or 1 mg (group 2) flumazenil were given, and the stage of coma, heart rate and 
blood pressure were again monitored. In a similar way, the effect of 5 and 1 mg 
flumazenil was investigated in 13 patients (group 3) and four patients (group 4) 
with ethanol intoxication. In an open trial, the clinical efficacy of flumazenil 
for the diagnosis of benzodiazepine or ethanol overdose was studied in 29 
patients (group 5). In all patients, a toxicological screening confirmed 
benzodiazepine or ethanol overdose. None of the patients receiving placebo 
showed effects on stage of coma, heart rate, blood pressure or respiratory rate. 
Patients with benzodiazepine overdose who received 5 mg flumazenil regained 
consciousness about 1-2 min after the end of injection. The effect of 1 mg 
flumazenil (group 2) on benzodiazepine-induced coma was less pronounced. In 
patients with ethanol overdose (group 3), ethanol-induced coma was reversed 
after 5 mg flumazenil more slowly than in patients of group 1. No effect of 
flumazenil on ethanol-induced coma was observed in group 4. In group 5, 
flumazenil proved to be useful for diagnosing benzodiazepine or ethanol 
intoxication. In one patient with coma due to carbamazepine overdose, flumazenil 
was also found to be effective. Additionally, a possible analytical interference 
of flumazenil and its metabolites with the identification of other 
benzodiazepines by a toxicological screening procedure was studied. Even after 
an oral dose of 200 mg flumazenil, no interference with immunological 
benzodiazepine assays (EMIT, TDX, and RIA) was found. A metabolite and an 
artifact of flumazenil could be identified in urine by gas chromatography/mass 
spectrometry.