Flunitrazepam
From Wikipedia, the free encyclopedia
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Flunitrazepam
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| Systematic (IUPAC) name | |
| 6-(2-fluorophenyl)-2-methyl-9-nitro- 2,5-diazabicyclo[5.4.0]undeca- 5,8,10,12-tetraen-3-one |
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| Identifiers | |
| CAS number | |
| ATC code | N05 |
| PubChem | |
| DrugBank | |
| Chemical data | |
| Formula | C16H12FN3O3 |
| Mol. mass | 313.3 |
| Pharmacokinetic data | |
| Bioavailability | 50% (suppository) 64-77% (oral) |
| Metabolism | Hepatic |
| Half life | 18-26 hours |
| Excretion | Renal |
| Therapeutic considerations | |
| Pregnancy cat. |
C(AU) |
| Legal status | |
| Routes | Oral |
Flunitrazepam (IPA: /ˌfluːnaɪˈtræzəpæm/) is a short-intermediate acting benzodiazepine derivative, marketed by Roche most commonly under the trade name Rohypnol. Flunitrazepam is also marketed in some countries under the trade names Hipnosedon, Hypnodorm, Nilium, Ilman and Insom. It is a highly-potent hypnotic drug with powerful sedative, anxiolytic, amnestic, and skeletal muscle relaxant properties.
It is commonly prescribed for the treatment of insomnia. Just as with other hypnotics, flunitrazepam should only be used on a short term basis or in those with chronic insomnia on an occasional basis.[1]
The drug is sometimes used as a date rape drug (commonly referred to in street slang as a "roofie").[2]
Flunitrazepam is classed as a nitrobenzodiazepine. Other nitrobenzodiazepines include nitrazepam and clonazepam.[3]
Contents |
[edit] Pharmacokinetics
While 80% of flunitrazepam that is taken orally is absorbed, bioavailability in suppository form is closer to 50%.[4]
Benzodiazepines such as flunitrazepam are lipophilic and rapidly penetrate membranes.
Flunitrazepam has a long half-life of 18 - 26 hours and an active metabolite which has a half life of 36-200 hours, which means flunitrazepam effects after nighttime administration persist throughout the next day.[5] Residual 'hangover' effects after nighttime administration of flunitrazepam such as sleepiness, impaired psychomotor and cognitive may persist into the next day which may impair the ability of users to drive safely and increase risks of falls and hip fractures.[6]
Flunitrazepam is lipophilic and is metabolised hepatically via oxidative pathways. The enzyme CYP3A4 is the main enzyme in its phase 1 metabolism.[7]
[edit] Pharmacology
Benzodiazepines, including flunitrazepam, bind to glial cell membranes with high affinity.[8] Flunitrazepam has an inhibitory effect on plasma cholinesterase of 60--90 per cent.[9] Flunitrazepam potently induces melanogenesis in melanoma cells via modulating high affinity binding sites.[10] Benzodiazepines, including flunitrazepam have been shown to act via micromolar benzodiazepine binding sites as Ca2+ channel blockers and significantly inhibit depolarization-sensitive calcium uptake.[11]
[edit] Desired effects
The main pharmacological effects of flunitrazepam are the enhancement of GABA at the GABAA receptor.[12] Like other benzodiazepines, flunitrazepam's pharmacological effects include sedation, muscle relaxation, reduction in anxiety, and prevention of convulsions.
Flunitrazepam's effects are approximately 7 to 10 times more potent than diazepam. The effects of flunitrazepam appear approximately 15 to 20 minutes after oral administration, and last for approximately four to six hours. Some residual effects can persist up to 12 hours or more after administration.
[edit] 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 floppy infant syndrome. Other adverse effects include cognitive and motor dysfunctions.
[edit] Dependence
Flunitrazepam as with other benzodiazepine drugs can lead to physical dependence, addiction and what is known as the benzodiazepine withdrawal syndrome.
Discontinuation may result in the appearance of withdrawal symptoms when the drug is discontinued. Abrupt withdrawal may lead to a severe benzodiazepine withdrawal syndrome characterised by seizures, psychosis, severe insomnia and severe anxiety. Rebound insomnia, worse than baseline insomnia, typically occur after discontinuation of flunitrazepam even after short term single nightly dose therapy.[13]
[edit] Sleep depth
Flunitrazepam produces a decrease in delta wave activity. The effect of benzodiazepine drugs on delta waves, however, may not be mediated via benzodiazepine receptors. Delta activity is an indicator of depth of sleep within non-REM sleep; increased levels of delta sleep reflects poorer quality of sleep. Thus flunitrazepam and other benzodiazepines cause a deterioration in sleep quality. Cyproheptadine may be superior to benzodiazepines in the treatment of insomnia as it enhances sleep quality based on EEG studies.[14] This may lead to somnolence.
[edit] Overdose
Flunitrazepam is a drug which is very frequently involved in drug intoxication, including overdose.[15] Overdose of flunitrazepam may result in excessive sedation, impairment of balance and 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 alcohol, opiates or other CNS depressants.
This lethal effect of flunitrazepam overdose is commonly used in suicide, as seen in Abuse potential section.
Flunitrazepam overdose responds to the benzodiazepine receptor antagonist flumazenil, which thus can be used as a treatment.
[edit] Floppy infant syndrome
- See also: Floppy infant syndrome
Benzodiazepines such as flunitrazepam are lipophilic and rapidly penetrate membranes and therefore rapidly crosses over into the placenta with significant uptake of the drug. Use of benzodiazepines including flunitrazepam in late pregnancy, especially high doses, may result in floppy infant syndrome.[16]
[edit] Other
After discontinuation of flunitrazepam a rebound effect may occur about 4 days after stopping flunitrazepam.[17] (See benzodiazepine withdrawal syndrome)
Flunitrazepam impairs cognitive functions. This may appear as a lack of concentration, confusion and anterograde amnesia. It can be described as a hangover-like effect, with impairment of mental arithmetic abilities.
Impaired psychomotor functions is another adverse effect, affecting reaction time and driving skill. This may also be expressed as impaired coordination, impaired balance and dizziness.
Other adverse effects include:
- Slurred speech
- Gastrointestinal disturbances, lasting 12 or more hours/Vomiting
- Respiratory depression in higher doses
[edit] Interactions
The use of flunitrazepam in combination with alcohol synergizes the adverse effects, and can lead to toxicity and death.
Benzodiazepines including flunitrazepam may inhibit the glucuronidation of morphine leading to increased levels of and prolongation of the effects of morphine.[18]
[edit] Neurosteroides
Flunitrazepam and other benzodiazepines may inhibit neurosteroid metabolism, with alterations in the levels of progesterone, which in turn may adversely influence the functions of the brain and reproductive system. The pharmacological actions of neurosteroids are similar to those of benzodiazepines, as they are positive allosteric modulators of the GABAa receptor, enhancing GABA function. Thus, long-term administration of benzodiazepines may influence the concentrations of endogenous neurosteroids, and thereby would modulate the emotional state. Factors which effects benzodiazepines ability to alter neurosteroid levels depend on the molecular make up of the individual benzodiazepine molecule.[19]
[edit] Medical uses
- In the United States, the drug has not been approved by the Food and Drug Administration for medical use, and is considered to be an illegal drug.[20][21][22]
- In the United Kingdom, the drug is available only by private prescription.[23] Though Rohypnol was discontinued in 1986, Flunitrazepam use is still present in modern culture; among other uses, it is used in some hospitals to sedate patients undergoing colonoscopy.
- In the Netherlands, flunitrazepam is a List 2 substance of the Opium Law and is available for prescription as 1mg Rohypnol brand tablets by Roche, and as 1mg and 2mg generic tablets.
- In Ireland, flunitrazepam is a Schedule 3 controlled substance with strict restrictions.[24]
- In Singapore, flunitrazepam is a Class C controlled drug, making it illegal to possess without a proper medical prescription.
- In Greece, flunitrazepam is available as Hipnosedon in 1mg preparation and as Vulbegal and Nilium in 2mg preparations.[25]
- In Australia, prescription is restricted as a Schedule 8 medicine.[26][27] It is used primarily for the treatment of severe insomnia that has not responded to other treatments. In some states, it is also manufactured in generic form by Alphapharm under the name Hypnodorm. As a Schedule 8 medicine, it is illegal to have this drug in possession without an authority prescription from a registered doctor.
- In South Africa, Rohypnol is classified as a schedule 6 drug.[28] It is available by prescription only, and restricted to 1 mg doses. Travelers from South Africa to the United States are limited to a 30-day supply. The drug must be declared to US Customs upon arrival. If a valid prescription cannot be produced, the drug may be subject to Customs search and seizure, and the traveler may face criminal charges or deportation.
- In Norway, flunitrazepam is available as a prescription drug to treat insomnia under the brand name Flunipam 1 mg. Only four hypnotics are prescribable in Norway: flunitrazepam, nitrazepam, zolpidem and zopiclone.[29]
- In Sweden, the brand Rohypnol has been withdrawn from the domestic market. It is available as a generic and under the name Fluscand. Although it has for a long time been a first line drug for the treatment of insomnia, due to the stigma connected to it, flunitrazepam prescriptions are very hard to get nowadays. Much more common are nitrazepam but above all zopiclone, zolpidem, and zaleplon.
- In Mexico, Rohypnol is approved for medical use,[22] however there have been many cases of trafficking of Rohypnol to the United States and other developed nations, most of it originating from Mexico.[30]
- In Germany, flunitrazepam is available as the Roche-Brand Rohypnol 1 mg Film-Coated Tablets and several generic 1 mg tablets (e.g. Fluninoc, Flunitrazepam ratiopharm, Flunitrazepam neuraxpharm). The prescription of flunitrazepam as a hypnotic is generally tended to be for short-term treatment of severe insomnias, that are not responsive to other hypnotics (though some physicians prescribe this preparate as the ultimate high-potency hypnotic in severe cases of insomnia even as first-line option), especially in inpatients. It is considered to be one of the most potent benzodiazepine hypnotic (rather on effect than on dose basis; i.e., its hypnotic effect is being considered to be one of the most strongly pronounced of all benzodiazepine hypnotics available). Abuse of flunitrazepam among drug addicts is considerable and any possession of flunitrazepam without a valid prescription is illegal.
[edit] Abuse potential
Despite the fact that flunitrazepam is a Schedule IV controlled substance, it is not commercially available in the United States. Currently the DEA is recommending that Rohypnol be reclassified to Schedule I.
[edit] Drug-facilitated sexual assault
Flunitrazepam is known to induce anterograde amnesia in sufficient doses; individuals are unable to remember certain events that they experienced while under the influence of the drug. This effect is particularly dangerous when flunitrazepam is used to aid in the commission of sexual assault; victims may not be able to clearly recall the assault, the assailant, or the events surrounding the assault.
It is difficult to estimate just how many flunitrazepam-facilitated rapes have occurred in the past. Very often, biological samples are taken from the victim at a time when the effects of the drug have already passed and only residual amounts remain in the body fluids. These residual amounts are difficult, and sometimes impossible, to detect using standard screening assays available in the United States. If flunitrazepam exposure is to be detected at all, urine samples need to be collected within 72 hours and subjected to sensitive analytical tests. The problem is compounded by the onset of amnesia after ingestion of the drug, which causes the victim to be uncertain about the facts surrounding the rape. This uncertainty may lead to critical delays or even reluctance to report the rape and provide appropriate biological samples for testing. If a person suspects that he or she is the victim of a flunitrazepam-facilitated rape, he or she should get laboratory testing for flunitrazepam as soon as possible. In recent news it has been discovered that scientists can now detect flunitrazepam and related compounds in urine at least up to 5 days after administration of a single dose of Rohypnol and up to a month in hair.[31]
It must be noted that an inability to remember events, including sexual encounters, is not conclusive evidence of having consumed a drugged drink: Drunkenness itself causes blackouts, sleepiness, and a reduction in inhibitions. Only a timely screening for flunitrazepam can demonstrate its use. It has been shown that alcohol alone is the substance used in the vast majority of cases of date-rape. A recent study conducted by doctors in the U.K. found that none of the subjects reporting spiked drinks had any traces of flunitrazepam or other medications popularly believed to be associated with rape such as GHB. The study claims that binge drinking was to blame.[32]
[edit] Drug-facilitated robbery
In the United Kingdom, the use of flunitrazepam and other "date rape" drugs has been connected to stealing from sedated victims. One expert quoted in a British newspaper estimated that up to 2,000 individuals are robbed each year after being spiked with powerful sedatives,[33] making drug-assisted robbery a more common problem than drug-assisted rape.
Criminals sometimes use flunitrazepam before committing robbery as it has a calming and anti-emotive effect. This allows the criminal to perform the robbery without becoming anxious. Flunitrazepam is also known to induce anterograde amnesia making police interrogations more difficult.[34][35][36]
In a notable flunitrazepam related case, Selina Hakki was found guilty in December 2004 of using flunitrazepam to drug wealthy men and rob them of their clothes and accessories in the UK.
[edit] Recreational drug
Although flunitrazepam has become widely known for its use as a date-rape drug, it is used more frequently as a recreational drug. It is used by high school and college students, rave party attendees, and heroin and cocaine users (who call a dose of flunitrazepam a "roofie") for recreational purposes, including:
- To produce profound intoxication (Kurt Cobain overdosed on a mixture of flunitrazepam and champagne several weeks before his death)
- To increase sedative effect in combination with heroin, or ease the anxiety and/or sleeplessness of withdrawal
- To counteract the side effects of stimulants (e.g. insomnia, paranoia, jitteriness)
- To "soften" the so-called "crash" which follows heavy usage of stimulants, such as cocaine or methamphetamine
Flunitrazepam is usually consumed orally, and is often combined with alcohol. It is also occasionally insufflated (i.e. tablets are crushed into powder and snorted). In some European countries, there was an alcohol solution of flunitrazepam (Darkene), taken by injection, with very strong effects.
Benzodiazepines, including diazepam, nitrazepam, oxazepam and flunitrazepam account for the largest volume of forged drug prescriptions in Sweden, a total of 52% of drug forgeries being for benzodiazepines, suggesting benzodiazepines are a major prescription drug class of abuse. Nitrazepam and flunitrazepam accounted for the vast majority of forged prescriptions.[37]
Flunitrazepam and other sedative hypnotic drugs are detected frequently in cases of people suspected of driving under the influence of drugs. Other benzodiazepines and zolpidem and zopiclone are also found in high numbers of suspected drugged drivers. Many drivers have blood levels far exceeding the therapeutic dose range suggesting a high degree of abuse potential for benzodiazepines and zolpidem and zopiclone.[38]
[edit] Suicide
Benzodiazepines were implicated in 39% of suicides by drug poisoning in Sweden, with nitrazepam and flunitrazepam accounting for 90% of benzodiazepine implicated suicides, in the elderly over a period of 2 decades. In three quarters of cases death was due to drowning, typically in the bath. Benzodiazepines were the predominant drug class used in suicides in this review of Swedish death certificates with 72% of benzodiazepine overdoses showing that benzodiazepines were the sole drug used in deaths by overdose. Benzodiazepines and in particular nitrazepam and flunitrazepam should therefore be prescribed with caution in the elderly.[39]It was also found that in about a third of overdose cases involving benzodiazepines, benzodiazepines were the sole cause of death.[40]
In a retrospective study of deaths, when benzodiazepines were implicated in the deaths, the benzodiazepines flunitrazepam and nitrazepam were the most common benzodiazepines involved. Benzodiazepines were a factor in all deaths caused by drug addiction in the study. Nitrazepam and flunitrazepam were significantly more commonly implicated in suicide related deaths than natural deaths. In four of the cases benzodiazepines alone were the only cause of death. It was concluded that flunitrazepam and nitrazepam were significantly more toxic than other benzodiazepines.[41]
[edit] Legal status
Flunitrazepam is currently a Schedule III drug under the international Convention on Psychotropic Substances of 1971;[42] in the United States, it is on Schedule IV
According to FDA Associate Director for Domestic and International Drug Control Nicholas Reuter:[43]
- Flunitrazepam was "temporarily controlled in Schedule IV pursuant to a treaty obligation under the 1971 Convention on Psychotropic Substances. At the time flunitrazepam was placed temporarily in Schedule IV . . . there was no evidence of abuse or trafficking of the drug in the United States."
Rohypnol is currently under consideration to be rescheduled to Schedule I, and is already considered such in the States of Florida, Idaho, Minnesota, New Hampshire, New Mexico, North Dakota, Oklahoma, and Pennsylvania.
and provide for stiff prison terms for the possession of flunitrazepam; penalties for use or distribution include life in prison, should death or serious injury occur.
In Australia, flunitrazepam is a schedule 8 drug, along with amphetamines and narcotic analgesics. All other benzodiazepines (except Temazepam) are schedule 4 drugs. Unauthorized possession of certain quantities of the drug is punishable by criminal sanctions in New South Wales under Schedule 1 of the Drug Misuse and Trafficking Act 1985.
On January 1, 2003 flunitrazepam was moved up one level in the schedule of controlled drugs and on August 1st 2004 the manufacturer Roche removed Rohypnol from the market.[44]
[edit] Alternatives
Intermediate half life benzodiazepines are also useful for patients with difficulty in maintaining sleep e.g. loprazolam, lormetazepam, temazepam and may be preferable to long half life benzodiazepines which typically cause next day sedation and impairments.
[edit] Street terms
Street names for Rohypnol include rophy, rufflels, roachies, roofies, ruffies, ruff up, rib, roach 2 (R2), roche, rope, ropies, circles, circes, forget it, forget-me-pill, Mexican Valium, and Run-Trip-And-Fall.[45][46]
[edit] History
Flunitrazepam was first synthesized in 1972 by Roche and was used in hospitals when deep sedation was needed. It first entered the commercial market in Europe in 1975 as Rohypnol produced by Roche, and in the 1980s it began to be available in other countries. It first appeared in the U.S. in the early 1990s. It originally came in 1 mg and 2 mg doses, but due to its potency and potential for abuse the higher doses of Rohypnol were soon taken off the market by its producer, Roche, and it is now only available as 1mg tablets. In the countries where flunitrazepam is available for prescription as both 1mg and 2mg tablets, such as the Netherlands, generic alternatives are available for the 2mg tablets.
[edit] See also
[edit] References
- Inchem - Retrieved 2007-2-27
[edit] Footnotes
- ^ Rickels K. (1986). "The clinical use of hypnotics: indications for use and the need for a variety of hypnotics.". Acta Psychiatrica Scandinavica Suppl. 332: 132-41. PMID 2883820.
- ^ http://www.usdoj.gov/dea/pubs/rohypnol/rohypnol.htm
- ^ Robertson MD; Drummer OH. (May 1995). "Postmortem drug metabolism by bacteria.". J Forensic Sci. 40 (3): 382-6. PMID 7782744.
- ^ Cano J. P.; Soliva, M.; Hartmann, D.; Ziegler, W. H.; Amrein, R. (1977). "Bioavailability from various galenic formulations of flunitrazepam". Arzneimittelforschung 27 (12): 2383-8.. rohypnol.
- ^ Benzodiazepine Equivalents Table - A list of Equivalent Doses of Benzodiazepines
- ^ Vermeeren A. (2004). "Residual effects of hypnotics: epidemiology and clinical implications.". CNS Drugs. 18 (5): 297-328. PMID 15089115.
- ^ CYP3A4 Is the Major CYP Isoform Mediating the in Vitro ...
- ^ Tardy M; Costa MF, Rolland B, Fages C, Gonnard P. (Apr 1981). "Benzodiazepine receptors on primary cultures of mouse astrocytes". J Neurochem 36 (4): 1587-9. PMID 6267195.
- ^ Holmes JH; Kanfer I, Zwarenstein H. (Aug 1978). "Effect of benzodiazepine derivatives on human blood cholinesterase in vitro.". Res Commun Chem Pathol Pharmacol 21 (2): 367-70. PMID 29327.
- ^ Matthew E; Laskin JD, Zimmerman EA, Weinstein IB, Hsu KC, Engelhardt DL (Jun 1981). "Benzodiazepines have high-affinity binding sites and induce melanogenesis in B16/C3 melanoma cells". Proc Natl Acad Sci U S A 78 (6): 3935-9. PMID 6267610.
- ^ Taft WC; DeLorenzo RJ (May 1984). "Micromolar-affinity benzodiazepine receptors regulate voltage-sensitive calcium channels in nerve terminal preparations". Proc Natl Acad Sci U S A 81 (10): 3118-22. PMID 6328498.
- ^ Oelschläger H. (4). "[Chemical and pharmacologic aspects of benzodiazepines]". Schweiz Rundsch Med Prax. 78 (27-28): 766-72. doi:. PMID 2570451.
- ^ Kales A; Scharf MB, Kales JD, Soldatos CR. (20). "Rebound insomnia. A potential hazard following withdrawal of certain benzodiazepines.". JAMA : the journal of the American Medical Association. 241 (16): 1692-5. PMID 430730.
- ^ Tokunaga S; Takeda Y, Shinomiya K, Hirase M, Kamei C. (Feb 2007). "Effects of some H1-antagonists on the sleep-wake cycle in sleep-disturbed rats." (pdf). J Pharmacol Sci. 103 (2): 201-6. PMID 17287588.
- ^ Zevzikovas A; Kiliuviene G, Ivanauskas L, Dirse V. (2002). "[Analysis of benzodiazepine derivative mixture by gas-liquid chromatography]". Medicina (Kaunas). 38 (3): 316-20. PMID 12474705.
- ^ Kanto JH. (May 1982). "Use of benzodiazepines during pregnancy, labour and lactation, with particular reference to pharmacokinetic considerations.". Drugs. 23 (5): 354-80. PMID 6124415.
- ^ Hindmarch I. (Nov 1977). "A repeated dose comparison of three benzodiazepine derivative (nitrazepam, flurazepam and flunitrazepam) on subjective appraisals of sleep and measures of psychomotor performance the morning following night-time medication.". Acta Psychiatrica Scandinavica 56 (5): 373-81. PMID 22990.
- ^ Pacifici GM; Gustafsson LL, Säwe J, Rane A. (Apr 1986). "Metabolic interaction between morphine and various benzodiazepines.". Acta Pharmacol Toxicol (Copenh). 58 (4): 249-52. PMID 2872767.
- ^ Usami N; Yamamoto T, Shintani S, Ishikura S, Higaki Y, Katagiri Y, Hara A. (Apr 2002). "Substrate specificity of human 3(20)alpha-hydroxysteroid dehydrogenase for neurosteroids and its inhibition by benzodiazepines." (pdf). Biol Pharm Bull. 25 (4): 441-5. PMID 11995921.
- ^ DEA Resources, For Law Enforcement Officers, Intelligence Reports, Rohypnol
- ^ Rohypnol Fast Facts
- ^ a b Women's Health.gov: Date Rape Drugs
- ^ "UK Rohypnol: The date rape drug", BBC News Online, Thursday, May 20, 1999. Retrieved on 2006-03-13.
- ^ Irish Statute Book, Statutory Instruments, S.I. No. 342/1993 — Misuse of Drugs (Amendment) Regulations, 1993
- ^ Å.Ï.Ö. ÁíáæÞôçóç öáñìáêåõôéêþí éäéïóêåõáóìÜôùí
- ^ Authorisation to Supply or Prescribe Drugs of Addiction: Flunitrazepam. Statutory Medical Notifications. Department of Health, Government of Western Australia (13 August 2004). Retrieved on 2006-03-13.
- ^ Guidelines for the Prescribing of Flunitrazepam (PDF). Pharmaceutical Services Branch. New South Wales Health (August 2000). Retrieved on 2006-03-13.
- ^ Drug Wars - About Drugs (11 October 2006).
- ^ Kayed K. (30). "[Insomnia and hypnotics]". Tidsskr Nor Laegeforen. 115 (9): 1087-90. PMID 7725291.
- ^ DEA Briefs & Background, Drugs and Drug Abuse, State Factsheets, Texas
- ^ Detection of "Date-Rape" Drugs in Hair and Urine, Final Report
- ^ Drug rape myth exposed as study reveals binge drinking is to blame | the Daily Mail
- ^ 'Rape drug' used to rob thousands | Special reports | Guardian Unlimited
- ^ "Bankrånare stärkte sig med Rohypnol?", DrugNews.
- ^ "Mijailovic var påverkad av våldsdrog", Sydsvenskan.
- ^ "Mijailovic var påverkad av våldsdrog", Expressen.
- ^ Bergman U; Dahl-Puustinen ML. (1989). "Use of prescription forgeries in a drug abuse surveillance network.". Eur J Clin Pharmacol. 36 (6): 621-3. PMID 2776820.
- ^ Jones AW; Holmgren A, Kugelberg FC. (Apr 2007). "Concentrations of scheduled prescription drugs in blood of impaired drivers: considerations for interpreting the results.". Ther Drug Monit. 29 (2): 248-60. PMID 17417081.
- ^ Carlsten, A; Waern M, Holmgren P, Allebeck P. (2003). "The role of benzodiazepines in elderly suicides.". Scand J Public Health. 31 (3): 224-8. PMID 12850977.
- ^ Drummer OH; Ranson DL. (Dec 1996). "Sudden death and benzodiazepines.". Am J Forensic Med Pathol. 17 (4): 336-42. PMID 8947361.
- ^ Ericsson HR; Holmgren P, Jakobsson SW, Lafolie P, De Rees B. (10). "[Benzodiazepine findings in autopsy material. A study shows interacting factors in fatal cases]". Läkartidningen. 90 (45): 3954-7. PMID 8231567.
- ^ Annual Estimates Of Requirements Of Narcotic Drugs, Manufacture Of Synthetic Drugs, Opium Production And Cultivation Of The
- ^ "Date Rape" Drugs
- ^ Bramness JG; Skurtveit S, Furu K, Engeland A, Sakshaug S, Rønning M. (23). "[Changes in the sale and use of flunitrazepam in Norway after 1999]". Tidsskr Nor Laegeforen. 126 (5): 589-90. PMID 16505866.
- ^ Rohypnol fact sheet at About.com Teen Advice
- ^ Facts about Rohypnol and other date rape drugs - Facts on Rohypnol
[edit] External links
- Drugs Factfile on Rohypnol all you need to know
- Flash animation about how flunitrazepam works (mechanism of action)
- Molecule of the Month
- Statement on "Date Rape" Drugs by Nicholas Reuter, M.P.H., Mar. 11, 1999.
- Club Drugs - Fact Sheet by Drug Policy Information Clearing House, United States.
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