Flunitrazepam (Rohypnol):   Uses, Dosage, Synthesis & Safety | 1mg & 2mg Insights

Flunitrazepam (Rohypnol): The Definitive Guide

Introduction to Flunitrazepam

Flunitrazepam, commonly known by its trade name Rohypnol, is a potent benzodiazepine renowned for its sedative, hypnotic, and amnesic effects. Despite its medical applications for severe insomnia and anesthesia in countries like the UK and Germany, it is infamously labeled the "date rape drug" due to its illicit use in incapacitating victims3515. Not approved in the U.S., it remains a Schedule IV controlled substance with severe trafficking penalties710.

Chemical Properties & Synthesis

Molecular Structure & Formula

• Chemical Formula: C₁₆H₁₂FN₃O₃

• Molecular Weight: 313.28 g/mol

• ATC Code: N05CD03 (classified as a hypnotic and sedative)58.

Flunitrazepam Synthesis

Developed in the 1960s by Hoffmann-La Roche, flunitrazepam is synthesized through a multi-step process involving nitration and fluorination of benzodiazepine precursors. Key patents highlight its derivation from nitrazepam, with modifications enhancing potency812.

Related Compounds: Flunitrazolam

Flunitrazolam, an analog, shares structural similarities but differs in pharmacokinetics. Though less documented, it underscores the diversity of benzodiazepine derivatives8.

Pharmacology & Mechanism of Action

How Flunitrazepam Works

Flunitrazepam enhances GABA activity at GABA-A receptors, inhibiting neuronal excitability. This results in:

• Sedation: 10–15x more potent than diazepam412.

• Anterograde Amnesia: Blocks memory formation, a key factor in its criminal misuse515.

• Muscle Relaxation: Reduces tension without significant respiratory depression at therapeutic doses4.

Pharmacokinetics

• Bioavailability: 64–77% (oral), 50% (suppository)58.

• Half-Life: 18–26 hours, with active metabolites prolonging effects512.

• Metabolism: Liver-mediated, producing 7-aminoflunitrazepam (primary metabolite)812.

Medical Uses & Dosage

Therapeutic Applications

1. Severe Insomnia: 1mg–2mg tablets taken orally at bedtime512.

2. Anesthesia Adjunct: Pre-operative sedation (0.02–0.03mg/kg IV)1215.

3. Dental Procedures: Used for conscious sedation, though recovery is slower than diazepam4.

Dosage Forms

• Flunitrazepam 1mg: Lower dose for elderly patients or mild cases12.

• Flunitrazepam 2mg: Standard dose for severe insomnia57.

Illicit Use & Risks

Date Rape & Recreational Misuse

• Street Names: Roofies, Rophies, Forget-Me-Pill715.

• Modus Operandi: Odorless, tasteless tablets dissolved in drinks to induce unconsciousness and memory loss515.

• Detection: Urine tests identify metabolites up to 28 days post-ingestion58.

Side Effects & Overdose

• Common: Drowsiness, dizziness, confusion, blurred vision47.

• Severe: Respiratory depression, coma, death (especially with alcohol)515.

• Withdrawal: Seizures, anxiety, insomnia upon discontinuation515.

Flunitrazepam

Flunitrazepam is a water-soluble benzodiazepine derivative that is chemically and pharmacologically related to diazepam and other drugs of this group. The chemical formula for flunitrazepam is 5-(o-fluorophenyl)-1,3-dihydro-1-methyl-7-nitro-2H-1,4-benzodiazepin-2-one. The sedative, antianxiety, amnesic, and muscle-relaxing properties of flunitrazepam are similar to those of diazepam except that its sedative and sleep-inducing properties are more pronounced and longer lasting than those of diazepam.57 Foreman58 reported flunitrazepam to be approximately 15 times as potent as diazepam and suggested that the drug be diluted before administration to ensure precise titration.

Flunitrazepam is available in a 1-ml ampule containing 2 mg. The manufacturer suggests diluting the drug with 1 ml of sterile water for injection before use, providing a solution of 1 mg/ml.58 Foreman, however, suggests that further dilution is warranted, recommending the dilution of 2 mg (1 ml) of flunitrazepam in 9 ml of sterile water, providing a solution of 0.2 mg/ml.58

Flunitrazepam is known on the street as “roofies.” It is sometimes snorted to offset cocaine withdrawal. It has also acquired the title “the date-rape drug” because of its ability to induce anterograde amnesia, preventing the victim from recalling specific events while under the influence of the drug.59

Following IV administration for the induction of general anesthesia, flunitrazepam produces its clinical effects within 1 to 3 minutes, and the peak effect is noted in 5 minutes. The duration of clinical action ranged from 10 to 60 minutes, with significant variation with dosage (1 to 6 mg). The α-half-lives and β-half-lives of flunitrazepam are 19 and 34 hours.

Human Pharmacokinetics

Flunitrazepam is readily absorbed from the gastro-intestinal tract. It is extensively metabolized in the liver to its major metabolites N-desmethylflunitrazepam, which has some intrinsic activity, and 7-aminoflunitrazepam, which is inactive. The Cytochromes P450 enzymes CYP2C19 and CYP3A4 mediate the oxidative metabolism of these two metabolites; other metabolites include 3-hydroxyflunitrazepam, 3-hydroxy-7-acetamidoflunitrazepam, and 7-amino-1-desmethylflunitrazepam. Flunitrazepam is excreted in the urine almost entirely as metabolites, both free and conjugated, with less than 1% as unchanged drug. About 10% of a dose is eliminated in the feces (Galichet, 2004). Flunitrazepam crosses the placental barrier and is distributed in breast milk.

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