Flumazenil is an imidazole derivative of the benzodiazepines and acts as an antidote (antidote) in benzodiazepine overdose. It cancels all effects of the benzodiazepines used in anesthetics or sleeping pills for sedation. Flumazenil also reverses the influences of other non-benzodiazepines that react by the same mechanism.
What is flumazenil?
Flumazenil cancels all the effects of the benzodiazepines used in anesthetics or sleeping pills for sedation. It is injected intravenously and acts relatively quickly. Flumazenil is a competitive antagonist and acts at the benzodiazepine binding site of the GABA receptor. As an antagonist, flumazenil exerts no effects of its own, but displaces benzodiazepines or even non-benzodiazepines from this receptor-binding site, thus stopping their effectiveness. As a chemical compound, flumazenil has a basic structure related to the benzodiazepines. It is, as mentioned earlier, an imidazole derivative of the benzodiazepines. Based on this similar structure, it can dock at the receptor binding site of GABA receptors and displace the actual active ingredients. Flumazenil exists as a white, crystalline powder that is very slightly soluble in water.
Pharmacologic action
The effect of flumazenil on the organism can be explained only in the context of the use of substances that exert an influence on GABA receptors in the sense that they affect the activity of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA). These substances are both so-called benzodiazepines and non-benzodiazepines, which can dock at GABA receptors with the result of increasing GABA activity. GABA, in turn, evokes the increase in the opening probability of the chloride channel, thus increasing the influx of chloride ions into the neurons. The chloride ions reduce the excitability of the neuron membrane. This results in an overall calming effect on the organism. Thus, it can be said that the benzodiazepines and the other substances acting at the GABA receptor, such as zopiclone, zolpidem, and zaleplon, exert an antianxiety, anticonvulsant, sleep-promoting, sedative, muscle-relaxing, and to some extent euphoric influence by increasing GABA activity. When used, however, flumazenil will also dock at the GABA receptor, but it will not exert any effects of its own. It does, however, displace the other active ingredients from the receptor and thus indirectly contributes to the reduction of GABA activity. All effects of the substances used are thus abolished during the influence of flumazenil. However, because flumazenil has a short half-life of 60 minutes, the effects of the benzodiazepines or the other substances return rapidly (rebound effect).
Medical application and use
The use of flumazenil is limited mainly to reversing the effects of benzodiazepines. It is commonly used as an antidote for overdose, termination of anesthetic effects, and misuse of benzodiazepines. In emergency medicine, flumazenil serves as a fast-acting antidote in suicidal attempts with sleeping pills. Since flumazenil does not exert its own effects, it is currently used only in this field. However, research results are reported that could also support its use in the clinical picture of hypersomnia (sleeping sickness). However, since the causes of hypersomnia are varied, more research would be needed before definitive use. Flumazenil is injected intravenously and acts relatively quickly. However, because of its short half-life of 60 minutes, its effect wears off after about 2 hours, at which time the benzodiazepines that have not yet been broken down become effective again until they, too, are completely broken down. Detoxification with flumazenil should therefore be accompanied by observation and, if necessary, performed several times to avoid the rebound effect as much as possible.
Risks and side effects
Side effects can, of course, occur with the use of flumazenil. Rapid injection of flumazenil should be avoided because it can then cause sudden states of agitation and anxiety. If the use of flumazenil has been preceded by prolonged treatment with high doses of benzodiazepines, typical withdrawal symptoms also often occur.Common side effects include nausea, vomiting, agitation, increase in heart rate, anxiety, and seizures. The use of flumazenil is also contraindicated during vital treatment with benzodiazepines. This is true when the use of benzodiazepines becomes necessary for life support in high-grade agitation states. Flumazenil should be used with special caution in cases of mixed intoxication of benzodiazepines with tri- or tetracyclic antidepressants.
