Pharmacology of flumazenil

@article{Whitwam1995PharmacologyOF,
  title={Pharmacology of flumazenil},
  author={James G. Whitwam and Roman Amrein},
  journal={Acta Anaesthesiologica Scandinavica},
  year={1995},
  volume={39}
}
  • J. Whitwam, R. Amrein
  • Published 1 December 1995
  • Medicine, Psychology, Biology
  • Acta Anaesthesiologica Scandinavica
Flumazenil, an imidazobenzodiazpine, is the first benzodiazepine antagonist available for clinical use. It is a specific competitive antagonist at benzodiazepine receptors, which are associated with receptors for gammaaminobutyric acid, the most important inhibitory neurotransmitter in the central nervous system. Administered orally, it has a low bioavailability and the preferred route is intravenous. Its usual clinical role is to reverse the effects of benzodiazepine sedation; however… 
A Risk-Benefit Assessment of Flumazenil in the Management of Benzodiazepine Overdose
TLDR
Caution should be exercised when using this agent in patients who have co-ingested chloral hydrate or carbamazepine or whose ECG shows abnormalities typical of those seen after overdose with tricyclic antidepressants (TCAs); the use of flumazenil in the presence of these drugs can sometimes induce treatable cardiac dysrrhythmia.
Benzodiazepines in the intensive care unit.
Intravenous flumazenil versus oxazepam tapering in the treatment of benzodiazepine withdrawal: a randomized, placebo‐controlled study
TLDR
The effectiveness of FLU may reflect its capacity to upregulate BZD receptors and to reverse the uncoupling between the recognition sites of BzD and GABA, on the GABA A macromolecular complex, that has been reported in tolerant subjects.
Continuous Infusion of Flumazenil in the Management of Benzodiazepines Detoxification
TLDR
Elastomeric FLU infusion for BzD detoxification is a feasible administration device to maintain adequate, constant, and tolerated FLU concentrations for reducing BZD withdrawal symptoms.
Flumazenil-induced ballism.
TLDR
It is conceivable that flumazenil may antagonize the GABA-benzodiazepine receptor complex and induce dopamine hypersensitivity, thus induce dyskinesic symptoms, and be used to reverse the adverse pharmacological effects of benzodiazepines.
A comparison of chlordiazepoxide, bretazenil, L838,417 and zolpidem in a validated mouse Vogel conflict test
TLDR
The novel GABAA receptor ligand L838,417 was anxiolytic in this mouse model, and unlike the non-selective compounds, had no effect on unpunished drinking.
Ascorbic acid antagonizes the sedative effect of diazepam possibly through inhibition of GABA(Aρ₁) and GABA(B1) receptors.
TLDR
DZP is a GABA receptor agonist and AA may reverse DZP-mediated sedative effects in a non-competitive binding fashion in mice through inhibition of GABA(Aρ₁) and GABA(B1) receptors.
Stressful reactions and panic attacks induced by flumazenil in chronic benzodiazepine users
TLDR
Caution should be exercised when giving flumazenil to panic patients who are taking BZDs as maintenance treatment, as it triggered a qualitatively different reaction amounting to a panic attack during infusion in nine out of 15 patients.
Restoration Of GABAA Receptor Function After Benzodiazepine Use: A Meta-Analysis
TLDR
A meta-analysis compiles multiple literature sources to determine novel ways to restore GABAA receptor function so that recovering patients can maintain long-term abstinence from BZDs.
...
...

References

SHOWING 1-10 OF 141 REFERENCES
Flumazenil: US clinical pharmacology studies.
TLDR
The minimal effective dose of flumazenil required to reverse the sedative, psychomotor and amnesic effects of benzodiazepines used to produce conscious sedation was determined and it was found that the 0.2 mg dose resulted in the greatest between subject variability and only partial rather than complete reversal.
Pharmacokinetics and Clinical Use of Flumazenil (Ro 15-1788)
TLDR
In several clinical studies intravenous doses down to 0.2mg of flumazenil initiated a rapid and reliable reversal of benzodiazepine-induced sedation, hypnosis or coma, which might be explained by a modulation of GABA-ergic activity.
The clinical anti-convulsant effects of flumazenil, a benzodiazepine antagonist.
TLDR
In patients treated chronically for periods of up to 42 months with flumazenil as monotherapy or as addition to basic therapy, the anti-convulsant effect was good or very good in 70% of the previously untreated (naive) patients and in about half of the patients who had epilepsy of long duration and had been treated already with standard anti- Convulsants.
Pharmacology of Dormicum (midazolam) and Anexate (flumazenil)
TLDR
The onset of effect immediately follows the diffusion of the substances into the CNS and can be observed within the first minutes following flumazenil or midazolam administration, which allows both drugs to be administered in repeated small bolus doses under close observation of the patient's reaction.
The preclinical pharmacology of flumazenil.
  • W. Haefely
  • Biology, Medicine
    European journal of anaesthesiology. Supplement
  • 1988
TLDR
Flumazenil has slight partial agonistic properties that can be seen as a built-in safety mechanism when used in reversing agonist effects and that may be of use in the treatment of epilepsies.
Toxicological investigations with the benzodiazepine antagonist flumazenil.
TLDR
The risk in man given therapeutic doses or even intentional or accidental overdoses of flumazenil is extremely small and there was no indication for mutagenic potential in vitro concerning induction of gene mutations or clastogenic effects.
The reversal of midazolam sedation with the benzodiazepine antagonist flumazenil (Anexate).
TLDR
In the endoscopy clinic, the use of flumazenil was perceived by clinicians to significantly improve the speed and quality of recovery.
Does the benzodiazepine antagonist Ro 15-1788 antagonize the action of ethanol?
TLDR
Ro 15-1788 might affect for a short while the action of ethanol by interfering with the benzodiazepine receptors by reversing transiently the ethanol-induced changes in total alpha, delta, and slow alpha bands.
Kindling and withdrawal changes at the benzodiazepine receptor
TLDR
The effects of inverse agonists after chronic treatment with inverse agonist themselves and with benzodiazepine agonists are studied to see if tolerance develops or whether an opposite change occurs.
...
...