Synthetic derivatives of this molecule led to the creation of benzodiazepines with potent anxiolytic and anticonvulsant activity and diminished sedative and muscle-relaxing properties. Other investigators simultaneously isolated a product produced by a Streptomyces species that had the basic 1,4-benzodiazepine structure. In 1977 radioligand binding identified specific high-affinity benzodiazepine binding sites. 33 This endeavor was initially unsuccessful but led to the promising γ-aminobutyric acid (GABA) hypothesis as the benzodiazepine mechanism of action. The initial work of Haefely and Hunkeler 67 on chlordiazepoxide synthesis led to an attempt to develop benzodiazepine derivatives that would act as antagonists. 15 Flumazenil is effective for overdoses of zolpidem and zaleplon, nonbenzodiazepines that interact with ω 1 receptors, a subclass of central benzodiazepine receptors. 71 Flumazenil was not effective in overdose of baclofen in which a benzodiazepine receptor is not involved. 4 Case reports raise the possibility of a role for flumazenil in patients with paradoxical reactions to therapeutic doses of benzodiazepines.

Flumazenil may be considered for patients with hepatic encephalopathy although further study is necessary before it can be recommended. Flumazenil has no role in the management of ethanol intoxication.

Because the duration of effect of flumazenil is shorter than that of most benzodiazepines, repeat doses may be necessary and vigilance is warranted. 21 Flumazenil is the ideal antidote for the relatively few patients who are both naïve to benzodiazepines and who overdose solely on a benzodiazepine as well as benzodiazepine-naïve patients whose benzodiazepine component must be reversed after procedural sedation. Flumazenil does not reliably reverse the respiratory depression induced by intravenous (IV) benzodiazepines. Flumazenil also has the potential to induce benzodiazepine withdrawal symptoms, including seizures in patients who are benzodiazepine dependent.

Its role in patients with an unknown overdose is limited because seizures and dysrhythmias may develop when the effects of a benzodiazepine are reversed if the patient has taken a mixed overdose. Flumazenil is a competitive benzodiazepine receptor antagonist.

Antidote of benzodiazepines