Flunitrazepam

Structural formula
General
Non-proprietary name	Flunitrazepam
other names	5- (2-fluorophenyl) -1-methyl-7-nitro-1,3-dihydro-2 H -1,4-benzodiazepin-2-one
Molecular formula	C 16 H 12 FN 3 O 3
Brief description	white or yellowish crystalline powder
External identifiers / databases
CAS number 1622-62-4 EC number 216-597-8 ECHA InfoCard 100,015,089 PubChem 3380 DrugBank DB01544 Wikidata Q62947
Drug information
ATC code	N05 CD03
Drug class	Hypnotic Benzodiazepine Sedative
properties
Molar mass	313.29 g · mol -1
Physical state	firmly
Melting point	170-172 ° C
pK s value	1.88
solubility	practically insoluble in water
safety instructions
Please note the exemption from the labeling requirement for drugs, medical devices, cosmetics, food and animal feed GHS labeling of hazardous substances Caution H and P phrases H: 302-319 P: 305 + 351 + 338
Toxicological data	1200 mg kg −1 ( LD 50 ,  mouse ,  oral ) 415 mg kg −1 ( LD 50 ,  rat ,  oral )
As far as possible and customary, SI units are used. Unless otherwise noted, the data given apply to standard conditions .

Flunitrazepam is an active ingredient from the group of benzodiazepines . It is mainly prescribed as a sleep aid and is used orally or intramuscularly before surgical or diagnostic interventions for premedication and occasionally afterwards for a short period to sedate the patient.

history

Flunitrazepam was first manufactured and patented by Hoffmann-La Roche in 1972 . The preparation came onto the European market in 1975 and has been approved outside of Europe since 1980.

synthesis

Flunitrazepam is produced in a six-step synthesis. In the first step, the 2-amino-5-chloro-2'-fluorobenzophenone is obtained in a Friedel-Crafts acylation from 4-chloroaniline and 2-fluorobenzoyl chloride in the presence of zinc chloride . This is converted into 2-amino-2'-fluorobenzophenone by reductive dehalogenation . The subsequent reaction with bromoacetyl bromide results in an acid amide intermediate which is cyclized to the basic structure of the active ingredient by means of ammonia . In the fifth and sixth synthesis step, the corresponding substitutions for the target compound are introduced via nitration with potassium nitrate and sulfuric acid and N - alkylation with methyl iodide .

effect

Flunitrazepam binds to GABA _A receptors in the central nervous system and strengthens the inhibiting mechanisms naturally present there, in which the neurotransmitter GABA (gamma-aminobutyric acid) is involved. Flunitrazepam influences GABA's own transmissions even in much smaller doses than other benzodiazepine derivatives. The sedative effect is about seven to ten times stronger than that of diazepam . Since the active ingredient is absorbed very quickly and almost completely by the body after oral ingestion, the effect occurs about 15 to 20 minutes after use and lasts between four and seven hours. Some effects can occur up to twelve hours after use.

Side effects

As with benzodiazepines : A dependency can occur after two weeks not only in the case of abuse , but also in the case of therapeutic use.

In a critical analysis of relevant studies with regard to a possible impairment of the ability to drive on the road after taking flunitrazepam, Kaufmann et al. 2004 concluded that despite the amount of data collected so far, no consensus could be found among researchers . The presumed impairing effect of flunitrazepam on the ability to drive could neither be confirmed nor refuted. Nevertheless, it is true that even when used as intended, this medicinal product can change the human ability to react to such an extent that the ability to actively drive or operate machines is impaired. Therefore, during the course of treatment with flunitrazepam and for 24 hours after the last administration of the medication, no motor vehicles should be driven or other activities carried out with which a patient could endanger himself or others.

This applies to a greater extent if alcohol is taken at the same time , as this, together with flunitrazepam , can lead to greater impairment of the movement sequences and the practiced behavior even ten hours after the last dose .

Especially in children and elderly patients there is the possibility of “paradoxical” (opposite) reactions. Then instead of reassurance, heightened aggressiveness, acute states of excitement, anxiety, increased muscle cramps, difficulty falling asleep and staying asleep, nightmares, hallucinations, depressive moods or occasionally even suicide risk . Treatment with flunitrazepam should then not be continued.

Use in pregnancy

There is clear evidence of risks to the human fetus . Flunitrazepam should not be used during pregnancy . Benzodiazepines like flunitrazepam are relatively lipophilic and can cross the placental barrier. The use of high doses of benzodiazepines later in pregnancy can cause hypotonia in the newborn .

Harmful use

In combination with alcohol or opioids it can lead to amnesia (memory gap), therefore flunitrazepam has the reputation of a date rape drug : Victims of rape or other criminal offenses often cannot remember details of what happened . In the 1990s in particular, the then colorless and tasteless tablets were misused for this purpose, mostly by adding them to drinks. In 1999, the manufacturer changed the composition so that the tablets produced since then have a bluish color, discolor liquids, clump and have a slightly bitter taste. In some countries, however, the old tablets are still available and are also still being marketed in their old form by some generic drug manufacturers and other companies.

At the end of the 1990s, the Narcotics Act was changed to the effect that initially the amount per pack could not be more than 20 mg. As a result, the 2 mg tablets previously available in boxes of 20 were only offered in boxes of 10. Another amendment to the BtMG in 1998 meant that the maximum amount per divided form (i.e. tablet or ampoule) could not contain more than 1 mg flunitrazepam.

With the 25th ordinance amending the narcotics law of March 3, 2011, the German government decided to subject flunitrazepam to the provisions of the BtMG without exception. The Federal Council approved this amending ordinance in its 882nd plenary session on April 15, 2011 (BR-Drs 130/11). There was a transition period of six months from the announcement of this amending regulation in the Federal Law Gazette. This period ended on November 1, 2011. Since then, flunitrazepam-containing drugs have only been available in Germany with a BtM prescription .

In Austria, flunitrazepam is subject to the Narcotics Act. From mid-December 2012, therefore, drugs containing flunitrazepam were only prescribed on prescription drugs. Monopreparations such as Somnubene and Guttanotte are no longer available and are no longer manufactured. By the way, there is no medical justification for prescribing flunitrazepam. This prescribes benzodiazepines, which tide in more slowly.

In the US , flunitrazepam is not approved as a drug and is considered an illegal drug. However, import for “personal use” remained possible for a long time with appropriate evidence and registration with customs. About 1.5 million units of flunitrazepam (2 mg each) reached the USA legally in this way, until this form of import was also banned in 1996. Despite the relatively generous prescribing practice of other benzodiazepines compared to Germany, there is a black market for flunitrazepam in many US regions. Especially in the south of the USA, along the border with Mexico, the substance is relatively easy and comparatively cheap to obtain.

Flunitrazepam is also used by illicit drug users . The tablets are on the black market as "Ruppies", "Ruffies", "Roofies" (especially common in America under this name) or "R2", but in German-speaking countries mainly as "Flunies / Flummis" (based on the ingredient flunitrazepam) , "Ropse", "Ro (s) chies" (after the manufacturer Roche ) or "Ropys" known. Especially in Austria, the names "Roiperl", "Ro", "Rippal", "Benzos", "Slow" (for benzodiazepines in general) or "Sommal" or "Sommerl" (after the trade name Somnubene) are often used. Although they are only "available" with a substitution recipe, they are still sold on the black market.

The remedy is particularly widespread in “ junkie ” scenes in which flunitrazepam - as an alternative or in addition to opiates - is usually injected. But the drug is also partly common among party drug users. a. to "come down" after consuming hallucinogenic drugs. The new legal situation has meant that flunitrazepam has lost its importance in Germany. Other benzodiazepines that are available without a BtM prescription are increasingly being used. Illegal imports from abroad have also increased.

Film and art

• The US comedy film Hangover from 2010 is about a film tear caused by accidental ingestion of "roofies" in an alcoholic drink.
• The 2000 film Chabrol's Sweet Poison by French director Claude Chabrol based on the novel The Chocolate Cobweb describes years of abuse of flunitrazepam as a sleep aid.
• The song Baby's Got a Temper of The Prodigy addressed the consumption of Rohypnol and received in the original version of a radio ban.
• A song from the third album "The botten is nådd" (2003) by the Swedish hippopotamus Timbuktu is entitled "Flunitrazepam".
• The film Thoroughbreds from 2017 describes in the final chapter the use of "roofies" to carry out a murder .

Trade names

Monopreparations

Fluninoc (D), Rohypnol (D, A, CH), as well as some generics (D)

See also

• Benzodiazepine abuse
• Ko drops

literature

• Reinhard Larsen: Anesthesia and intensive medicine in cardiac, thoracic and vascular surgery. (1st edition 1986) 5th edition, Springer, Berlin / Heidelberg / New York [u. a.] 1999, ISBN 3-540-65024-5 , p. 26.

Web links

Commons : Flunitrazepam  - collection of images, videos and audio files

• Flunitrazepam . In: Erowid . (English)

Individual evidence

1. ↑ ^{a b c d} Entry on flunitrazepam. In: Römpp Online . Georg Thieme Verlag, accessed on July 1, 2019.
2. ↑ ^{a b} Flunitrazepam data sheet from Sigma-Aldrich , accessed on April 1, 2011 ( PDF ).
3. ^ ^{A b c} A. Kleemann , J. Engel, B. Kutscher, D. Reichert: Pharmaceutical Substances - Synthesis, Patents, Applications , 4th edition (2001) Thieme-Verlag Stuttgart, ISBN 978-1-58890-031-9 .
4. ↑ W. Hafely, E. Kyburz, M. Gerecke, H. Möhler, Adv. Drug Res. 14: 165-322 (1985).
5. ^ F. von Bruchhausen, S. Ebel, A. W. Frahm, E. Hackenthal: Hager's Handbook of Pharmaceutical Practice: Volume 8, Materials E – O. 5th edition, Birkhäuser, 1993, ISBN 3-540-52688-9 , p. 243.
6. ^ RM Kaufmann, R. Frey, HJ Battista, S. Kasper: Flunitrazepam and driving ability. In: Advances in Neurology and Psychiatry. 72, 2004, pp. 503-515, doi : 10.1055 / s-2003-812459 .
7. ^ Specialist information from the Swiss Medicines Compendium: Rohypnol®, as of March 2004.
8. ↑ Kanto JH: Use of benzodiazepines during pregnancy, labor and lactation, with particular reference to pharmacokinetic considerations . In: Drugs . 23, No. 5, May 1982, pp. 354-380. PMID 6124415 .
9. ↑ Twenty-fifth ordinance amending the law on narcotics. Ordinance of the Federal Government, Bundesrat Drucksache 130/11 of March 3, 2011.
10. ↑ USA imposes import ban on flunitrazepam
11. ↑ PRODIGY SINGLE 'TEMPER'ED BY RADIO Article on nme.com (English). Retrieved July 23, 2015.

This article is about a health issue. It is not used for self-diagnosis and does not replace a diagnosis by a doctor. Please note the information on health issues !