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Flumazenil (also known as flumazepil, code name Ro 15-1788 [3]) is a selective GABA A receptor antagonist [4] administered via injection, otic insertion, or intranasally. Therapeutically, it acts as both an antagonist and antidote to benzodiazepines (particularly in cases of overdose), through competitive inhibition .
Flumazenil was found to be more effective than placebo in reducing feelings of hostility and aggression in patients who had been free of benzodiazepines for 4–266 weeks. [92] This may suggest a role for flumazenil in treating protracted benzodiazepine withdrawal symptoms.
Due to its short half life, the duration of action of flumazenil is usually less than 1 hour, and multiple doses may be needed. [48] When flumazenil is indicated the risks can be reduced or avoided by slow dose titration of flumazenil. [47]
Flumazenil raises concerns with its tendency to induce benzodiazepine withdrawal, and symptoms include seizures and agitation. When a patient overdoses intentionally, benzodiazepines can actually mediate the effects of other lethal drugs in the system, so flumazenil's action to reverse its effects can actually be harmful. [6]
GABA receptor antagonists are drugs that inhibit the action of GABA. In general these drugs produce stimulant and convulsant effects, and are mainly used for counteracting overdoses of sedative drugs. Examples include bicuculline, securinine and metrazol, and the benzodiazepine GABA A receptor antagonist flumazenil.
In terms of the mechanism of action of benzodiazepines, their similarities are too great to separate them into individual categories such as anxiolytic or hypnotic. For example, a hypnotic administered in low doses produces anxiety-relieving effects, whereas a benzodiazepine marketed as an anti-anxiety drug at higher doses induces sleep. [182]
Flumazenil is uniquely poised as an "antidote" that specifically counteracts damaging central nervous system affect induced via benzodiazepine mechanism of action - though is not generally indicated in relation to the severity of symptoms where other treatment options exist, and often has numerous damaging consequences that must be carefully ...
Bretazenil (Ro16-6028) is an imidazopyrrolobenzodiazepine [1] anxiolytic drug which is derived from the benzodiazepine family, and was invented in 1988. It is most closely related in structure to the GABA antagonist flumazenil, although its effects are somewhat different.
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