Flumazenil (Ro 15-1788) antagonizes the benzodiazepine binding site of the gamma-aminobutyric acid (GABA)/benzodiazepine receptor complex in the central nervous system (CNS), thereby preventing the chloride channel opening events and inhibiting neuronal hyperpolarization. As a result, flumazenil reverses benzodiazepine-induced effects including sedation, psychomotor deficits, amnesia, and hypoventilation in a dose-dependent manner. Flumazenil is an imidazobenzodiazepine derivative, effective in reversing benzodiazepine-induced activities.

Flumazenil (1 mg/kg) demonstrated significant anxiolytic effects in BALB/c mice during elevated plus-maze and light/dark box tests. At a dose of 3 mg/kg, Flumazenil prevented changes induced by chronic ethanol withdrawal in mice, observed as decreased open arm time and the percentage of open arm entries. In rats, Flumazenil (10 mg/kg) effectively counteracted the sedative action produced by tetrahydroprogesterone. Additionally, Flumazenil antagonized the effects of diazepam in mice at doses ranging from 5-20 mg/kg, yet showed no effect on the anticonvulsant and adverse reactions associated with GYKI52466. While minimally decreasing the anticonvulsant activity of NBQX in the MES model and not in the PTZ test, Flumazenil binds to central benzodiazepine (BZD) receptors, thus antagonizing or reversing the neuropsychological and electrophysiological effects of BZD inverse agonists and agonists. Flumazenil can reverse sedative toxic reactions caused by the combined use of BZDs and other drugs, but it is ineffective in the case of cyclic antidepressant overdose.