Flumazenil

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Structural formula
Structural formula of flumazenil
General
Non-proprietary name Flumazenil
other names
  • 8-fluoro-5-methyl-6-oxo-5,6-dihydro-4 H -imidazo [1,5- a ] [1,4] benzo-diazepine-3-carboxylic acid ethyl ester ( IUPAC )
  • Flumazenilum ( Latin )
Molecular formula C 15 H 14 FN 3 O 3
Brief description

white to almost white, crystalline powder

External identifiers / databases
CAS number 78755-81-4
EC number 616-650-9
ECHA InfoCard 100.128.069
PubChem 3373
DrugBank DB01205
Wikidata Q421920
Drug information
ATC code

V03 AB25

Drug class

Antidote , benzodiazepine - antagonist

Mechanism of action

Competitive antagonist at the GABA A receptor

properties
Molar mass 303.29 g · mol -1
Physical state

firmly

Melting point

201-203 ° C

solubility
safety instructions
Please note the exemption from the labeling requirement for drugs, medical devices, cosmetics, food and animal feed
GHS labeling of hazardous substances
no GHS pictograms
H and P phrases H: no H-phrases
P: no P-phrases
Toxicological data

143 mg kg −1 ( LD 50 ,  mouse ,  iv )

As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Flumazenil is a Imidazobenzodiazepin- derivative and a benzodiazepine - antagonist . It is used as an antidote to drugs of the benzodiazepine group and other non-benzodiazepine agonists that attack the benzodiazepine binding site, such as zopiclone , zolpidem and zaleplon , and neutralizes all of their effects.

Pharmacodynamics

Flumazenil acts as a reversible, competitive antagonist at the benzodiazepine binding site of the GABA A receptor .

Pharmacokinetics

It must be given intravenously , as it is largely broken down by the liver when given orally (first-pass effect). The effect sets in quickly (two minutes), but only lasts for a relatively short time (two hours). Therefore, with longer-acting benzodiazepines there is a risk of a setback ( rebound effect ), the re-setting effect after this time.

Indications

  • Cancellation of benzodiazepine sedation / overdose
  • Termination of benzodiazepine anesthesia

Latest research shows that flumazenil could be effective in treating primary hypersomnia .

Side effects and contraindications

In addition to headaches , visual disturbances , nausea and vomiting , fear and restlessness occur. Benzodiazepine addicts can develop an acute withdrawal syndrome .

Flumazenil is contraindicated in patients who are hypersensitive to benzodiazepines or who have received benzodiazepines for the treatment of potentially life-threatening conditions (e.g. control of intracranial pressure after severe traumatic brain injury or status epilepticus). Although no controlled studies in pregnant women are available, animal experiments have not shown any teratogenic effects.

In high doses, people with a benzodiazepine dependence can trigger withdrawal symptoms, such as fear or tremor .

A single injection of a higher dose can cause pain, which is why flumazenil should be administered with a delayed release.

Chemical and physical properties

Flumazenil is hardly soluble in water, but easily soluble in dichloromethane . Various polymorphic forms are not yet known.

Individual evidence

  1. ↑ a b European Pharmacopoeia Commission (ed.): EUROPEAN PHARMACOPOE 5TH EDITION . tape 5.0-5.8 , 2006.
  2. ↑ a b c Entry on flumazenil in the ChemIDplus database of the United States National Library of Medicine (NLM) .
  3. ↑ Flumazenil data sheet from Sigma-Aldrich , accessed on January 4, 2013 ( PDF ).
  4. ^ DB Rye et al., Modulation of Vigilance in the Primary Hypersomnias by Endogenous Enhancement of GABAA Receptors. Sci. Transl. Med. 4, 161ra151 (2012) .
  5. ↑ Aktories et al .: General and Special Pharmacology and Toxicology , 9th edition, ISBN 978-3-437-44490-6 , p. 281.
  6. ↑ A. Doenicke et al .: antagonism of benzodiazepines with Ro15-1788. Overview and own clinical-experimental investigations. In: Anaesthesiologist . tape 33 , 1984, pp. 527-528 .

Trade names

Flumazenil is commercially available in Germany, Austria and Switzerland under the name Anexate and as a generic .

Web links

  • Entry on Flumazenil at Vetpharm, accessed on June 23, 2012.