Flumazenil Stats & Data
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DrugBankDescription
Fumazenil is an imidazobenzodiazepine derivative and a potent benzodiazepine receptor antagonist that competitively inhibits the activity at the benzodiazepine recognition site on the GABA/benzodiazepine receptor complex, thereby reversing the effects of benzodiazepine on the central nervous system.
Mechanism of Action
Flumazenil, an imidazobenzodiazepine derivative, is a benzodiazepine antagonist. It competitively inhibits the benzodiazepine binding site on the GABA/benzodiazepine receptor complex. Flumazenil is a weak partial agonist in some animal models of activity, but has little or no agonist activity in man.
Pharmacodynamics
Flumazenil antagonizes the CNS effects produced by benzodiazepines, but does not antagonize the central nervous system effects of drugs affecting GABA-ergic neurons by means other than the benzodiazepine receptor (including ethanol, barbiturates, or general anesthetics) and does not reverse the effects of opioids.
Metabolism
Hepatic. Flumazenil is completely (99%) metabolized. The major metabolites of flumazenil identified in urine are the de-ethylated free acid and its glucuronide conjugate.
Indication
For the complete or partial reversal of the sedative effects of benzodiazepines in cases where general anesthesia has been induced and/or maintained with benzodiazepines, and where sedation has been produced with benzodiazepines for diagnostic and therapeutic procedures. Also for the management of benzodiazepine overdose as an adjunct for appropriate supportive and symptomatic measures.
Half-life
Initial distribution half-life is 4 to 11 minutes and the terminal half-life is 40 to 80 minutes. Prolongation of the half-life to 1.3 hours in patients with moderate hepatic impairment and 2.4 hours in severely impaired patients. Compared to adults, the elimination half-life in pediatric patients was more variable, averaging 40 minutes (range: 20 to 75 minutes).
Protein Binding
Protein binding is approximately 50%, mostly (66%) to albumin. Protein binding is reduced in patients with hepatic cirrhosis.
Elimination
Flumazenil is completely (99%) metabolized. Elimination of radiolabeled drug is essentially complete within 72 hours, with 90% to 95% of the radioactivity appearing in urine and 5% to 10% in the feces.
Clearance
* 1 L/hr/kg healthy volunteers receiving a 5-minute infusion of a total of 1 mg
Measured Affinities
Guide to PHARMACOLOGYMeasured binding and functional data for flumazenil, curated by the IUPHAR/BPS Guide to PHARMACOLOGY. Each row cites the paper it came from. Lower concentrations mean tighter binding — a value in the sub-nanomolar range indicates a very potent interaction.
| Target | Action | Measure | Value | Concentration | Species | Source |
|---|---|---|---|---|---|---|
| GABAA receptor α5 subunit GABRA5 | Allosteric modulator | pKi | 9.22 | 0.603 nM | Human | PMID 30275042 |
| GABAA receptor α1 subunit GABRA1 | Antagonist | pKi | 9.1 | 0.794 nM | Human | PMID 30275042 |
| GABAA receptor α2 subunit GABRA2 | Allosteric modulator | pKi | 9.05 | 0.891 nM | Human | PMID 30275042 |
| GABAA receptor α3 subunit GABRA3 | Allosteric modulator | pKi | 8.98 | 1.05 nM | Human | — |
| GABAA receptor α4 subunit Gabra4 | Positive | pKi | 7.03 | 93.33 nM | Rat | PMID 7799410 |
| GABAA receptor α6 subunit GABRA6 | Partial agonist | pKi | 6.83 | 147.91 nM | Human | PMID 30275042 |
Reading this. pKi, pEC50 and pIC50 are negative log molar values, so a higher number means a tighter interaction; the concentration column converts them for you. Values from non-human species are laboratory measurements and do not translate directly to human effect. Receptor affinity is not a dose — it describes what a molecule binds, not how much of it is safe to take.
Receptor data from the IUPHAR/BPS Guide to PHARMACOLOGY (v2026.2), licensed CC BY-SA 4.0. Matched to this substance by InChIKey.
Flumazenil has some associations with the precipitation of seizures in patients with benzodiazepine dependency with a history of seizures. However, flumazenil overdose is extremely rare. Clinical Features * Anxiety
Liver injury risk
No documented concern
Toxicity (DrugBank)
In clinical studies, most adverse reactions to flumazenil were an extension of the pharmacologic effects of the drug in reversing benzodiazepine effects.
Effect Profile
CuratedLow anxiolysis and sedation
Tolerance & Pharmacokinetics
drugs.wikiTolerance Decay
Acute tolerance: develops within a single session — the reset numbers above apply after sustained heavy use, not after one binge. Within-session tachyphylaxis usually resets largely overnight.