Detail:

        Flunitrazepam, also known as Rohypnol among other names, is an intermediate acting benzodiazepine used in some countries to treat severe insomnia and in fewer, early in anesthesia.

        Just as with other hypnotics, flunitrazepam should be strictly used only on a short-term basis or by those with chronic insomnia on an occasional basis. Flunitrazepam has been referred to as a date rape drug even though its incidence is very rare in reported rape cases.

Use:

        In countries where the drug is still used, it is used for treatment of insomnia, and in some countries to begin anesthesia as well;these were also the indications in which it was originally studied.

Adverse effects:

        Adverse effects of flunitrazepam include dependence, both physical and psychological; reduced sleep quality resulting in somnolence; and overdose, resulting in excessive sedation, impairment of balance and speech, respiratory depression or coma, and possibly death. Because of the latter, flunitrazepam is commonly used in suicide. When used in pregnancy, it might cause hypotonia.

Dependence:

        Flunitrazepam as with other benzodiazepines can lead to drug dependence and benzodiazepine withdrawal syndrome.Discontinuation may result in the appearance of withdrawal symptoms when the drug is discontinued. Abrupt withdrawal may lead to a benzodiazepine withdrawal syndrome characterised by seizures, psychosis, insomnia, and anxiety. Rebound insomnia, worse than baseline insomnia, typically occurs after discontinuation of flunitrazepam even after short-term single nightly dose therapy.

Interactions:

        The use of flunitrazepam in combination with alcoholic beverages synergizes the adverse effects, and can lead to toxicity and death.

Overdose:

        Flunitrazepam is a drug that is frequently involved in drug intoxication, including overdose. Overdose of flunitrazepam may result in excessive sedation, or impairment of balance or speech. This may progress in severe overdoses to respiratory depression or coma and possibly death. The risk of overdose is increased if flunitrazepam is taken in combination with CNS depressants such as ethanol (alcohol) and opioids. Flunitrazepam overdose responds to the benzodiazepine receptor antagonist flumazenil, which thus can be used as a treatment.

Pharmacology:

        The main pharmacological effects of flunitrazepam are the enhancement of GABA at various GABA receptors.

While 80% of flunitrazepam that is taken orally is absorbed, bioavailability in suppository form is closer to 50%.

Flunitrazepam has a long half-life of 18–26 hours, which means that flunitrazepam's effects after nighttime administration persist throughout the next day.

        Flunitrazepam is lipophilic and is metabolised hepatically via oxidative pathways. The enzyme CYP3A4 is the main enzyme in its phase 1 metabolism in human liver microsomes.

Chemistry:

        Flunitrazepam is classed as a nitro-benzodiazepine. It is the fluorinated N-methyl derivative of nitrazepam. Other nitro-benzodiazepines include nitrazepam (the parent compound), nimetazepam (methylamino derivative) and clonazepam (2ʹ-chlorinated derivative).

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