Open Access Articles- Top Results for Flurazepam


Systematic (IUPAC) name
Clinical data
Trade names Dalmane
AHFS/ monograph
MedlinePlus a682051
  • X (Contraindicated in pregnancy)
Pharmacokinetic data
Bioavailability 83%
Metabolism Hepatic
Half-life 40–250 hours
Excretion Renal
17617-23-1 7pxY
PubChem CID 3393
DrugBank DB00690 7pxY
ChemSpider 3276 7pxY
UNII IHP475989U 7pxY
KEGG D00329 7pxY
PDB ligand ID FL7 (PDBe, RCSB PDB)
Chemical data
Formula C21H23ClFN3O
387.88 g/mol
Physical data
Melting point Script error: No such module "convert".
 14pxY (what is this?)  (verify)

Flurazepam[1] (marketed under the brand names Dalmane and Dalmadorm) is a drug which is a benzodiazepine derivative. It possesses anxiolytic, anticonvulsant, sedative and skeletal muscle relaxant properties. It produces a metabolite with a very long half-life (40–250 hours), which may stay in the bloodstream for up to four days.[2][unreliable source?] Flurazepam is therefore unsuitable as a sleeping medication for some individuals due to next-day sedation; however, this same effect may also provide next-day anxiety relief. For this reason it is sometimes utilized to treat anxiety-induced insomnia on the night before dental visits and other medical procedures, patients are usually instructed to have someone to drive them to and from the appointment when using flurazepam in this context.


Flurazepam is officially indicated for mild to moderate insomnia and as such it is used for short-term treatment of patients with mild to moderate insomnia such as difficulty falling asleep, frequent awakening, early awakenings or a combination of each. Flurazepam is a long-acting benzodiazepine and is sometimes used in patients who have difficulty in maintaining sleep. Intermediate half-life benzodiazepines are also useful for patients with difficulty in maintaining sleep (e.g. loprazolam, lormetazepam, temazepam). Hypnotics should only be used on a short term basis or in those with chronic insomnia on an occasional basis.[3]

Side effects

The most common adverse effects are dizziness, drowsiness, lightheadedness, and ataxia. Flurazepam has abuse potential and should never be used with alcoholic beverages or any other substance that can cause drowsiness. Additive and possibly fatal results may occur. Flurazepam users should only take this drug strictly as prescribed, and should only be taken directly before the user plans on sleeping a full night. Next day drowsiness is common and may increase during the initial phase of treatment as accumulation occurs until steady-state plasma levels are attained.

Tolerance, dependence and withdrawal problems

A review paper found that long term use of flurazepam is associated with drug tolerance, drug dependence, rebound insomnia and CNS related adverse effects. Flurazepam is best used for a short time period and at the lowest possible dose to avoid complications associated with long term use. Non-pharmacological treatment options however, were found to have sustained improvements in sleep quality.[4] Flurazepam and other benzodiazepines such as fosazepam, and nitrazepam lost some of their effect after seven days administration in psychogeriatric patients.[5] Flurazepam shares cross tolerance with barbiturates and barbiturates can easily be substituted by flurazepam in those who are habituated to barbiturate sedative hypnotics.[6]

After discontinuation of flurazepam a rebound effect or benzodiazepine withdrawal syndrome may occur about four days after discontinuation of medication.[7]

Contraindications and special caution

Benzodiazepines require special precaution if used in the elderly, during pregnancy, in children, alcohol- or drug-dependent individuals and individuals with comorbid psychiatric disorders.[8]


Flurazepam, similar to other benzodiazepines and nonbenzodiazepine hypnotic drugs causes impairments in body balance and standing steadiness in individuals who wake up at night or the next morning. Falls and hip fractures are frequently reported. The combination with alcohol increases these impairments. Partial, but incomplete tolerance develops to these impairments.[9] An extensive review of the medical literature regarding the management of insomnia and the elderly found that there is considerable evidence of the effectiveness and durability of non-drug treatments for insomnia in adults of all ages and that these interventions are underutilized. Compared with the benzodiazepines including flurazepam, the nonbenzodiazepine sedative-hypnotics appeared to offer few, if any, significant clinical advantages in efficacy in elderly persons. Tolerability in elderly patients, however, is improved marginally in that benzodiazepines have moderately higher risks of falls, memory problems, and disinhibition ("Paradoxical agitation") when compared to non-benzodiazepine sedatives. It was found that newer agents with novel mechanisms of action and improved safety profiles, such as the melatonin agonists, hold promise for the management of chronic insomnia in elderly people. Chronic use of sedative-hypnotic drugs for the management of insomnia does not have an evidence base and has been discouraged due to concerns including potential adverse drug effects as cognitive impairment (anterograde amnesia), daytime sedation, motor incoordination, and increased risk of motor vehicle accidents and falls. In addition, the effectiveness and safety of long-term use of sedative hypnotics has been determined to be no better than placebo after 3 months of therapy and worse than placebo after 6 months of therapy. (NEJM, 1983, 1994, et seq.)[10]


Flurazepam is a "classical" benzodiazepine; some other classical benzodiazepines include diazepam, clonazepam, oxazepam, lorazepam, nitrazepam, bromazepam, and clorazepate.[11] Flurazepam generates an active metabolite with a very long elimination half-life of 40–250 hours.[2][unreliable source?] Residual 'hangover' effects after nighttime administration of flurazepam, such as sleepiness, impaired psychomotor and cognitive functions, may persist into the next day, which may impair the ability of users to drive safely and increase risks of falls and hip fractures.[12]

Flurazepam is lipophilic, is metabolized hepatically via oxidative pathways. The main pharmacological effect of flurazepam is to increase the effect of GABA at the GABAA receptor via binding to the benzodiazepine site on the GABAA receptor causing an increase influx of chloride ions into the GABAA neuron.[13][14] Flurazepam is a unique benzodiazepine in that it is a partial agonist of benzodiazepine receptors whereas other benzodiazepines are full agonists of benzodiazepine receptors.[15]

Flurazepam is contraindicated in pregnancy. It is recommended to withdraw flurazepam during breast feeding, as flurazepam is excreted in breast milk.[16]

Drug misuse

Flurazepam is a drug with potential for misuse. Two types of drug misuse can occur, either recreational misuse where the drug is taken to achieve a high, or when the drug is continued long term against medical advice.[17]

Legal status

Flurazepam is a Schedule IV drug under the Convention on Psychotropic Substances.[18]


Inclusion of fluorine on the pendant aromatic ring, and the basic side chain seems to emphasize/accentuate the anticonvulsant and hypnotic effects of this class of drugs.

File:Flurazepam synthesis.svg
Flurazepam synthesis:[19] Prepn:[20][21][22] all to Hoffmann-La Roche. Manuf process:[23] Synthesis:[24]

Thus alkylation of the benzodiazepam 3 (prepared from the corresponding substituted aminobenzophenone), with 2-chlorotriethylamine via its sodium salt affords Flurazepam (4).

See also


  1. ^ BE 629005 
  2. ^ a b "Benzodiazepine Equivalents Table - A list of Equivalent Doses of Benzodiazepines". Retrieved 2015-05-05. 
  3. ^ Rickels K. (1986). "The clinical use of hypnotics: indications for use and the need for a variety of hypnotics". Acta Psychiatrica Scandinavica Suppl. 74 (S332): 132–41. PMID 2883820. doi:10.1111/j.1600-0447.1986.tb08990.x. 
  4. ^ Kirkwood CK (1999). "Management of insomnia". J Am Pharm Assoc (Wash) 39 (5): 688–96; quiz 713–4. PMID 10533351. 
  5. ^ Viukari M; Linnoila M; Aalto U. (January 1978). "Efficacy and side effects of flurazepam, fosazepam, and nitrazepam as sleeping aids in psychogeriatric patients". Acta Psychiatrica Scandinavica 57 (1): 27–35. PMID 24980. doi:10.1111/j.1600-0447.1978.tb06871.x. 
  6. ^ Rooke KC. (1976). "The use of flurazepam (dalmane) as a substitute for barbiturates and methaqualone/diphenhydramine (mandrax) in general practice". J Int Med Res. 4 (5): 355–9. PMID 18375. doi:10.1177/030006057600400510. 
  7. ^ Hindmarch I. (November 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. doi:10.1111/j.1600-0447.1977.tb06678.x. 
  8. ^ Authier, N.; Balayssac, D.; Sautereau, M.; Zangarelli, A.; Courty, P.; Somogyi, AA.; Vennat, B.; Llorca, PM.; Eschalier, A. (November 2009). "Benzodiazepine dependence: focus on withdrawal syndrome". Ann Pharm Fr 67 (6): 408–13. PMID 19900604. doi:10.1016/j.pharma.2009.07.001. 
  9. ^ Mets, MA.; Volkerts, ER.; Olivier, B.; Verster, JC. (Feb 2010). "Effect of hypnotic drugs on body balance and standing steadiness.". Sleep Med Rev 14 (4): 259–67. PMID 20171127. doi:10.1016/j.smrv.2009.10.008. 
  10. ^ Bain KT (June 2006). "Management of chronic insomnia in elderly persons". Am J Geriatr Pharmacother 4 (2): 168–92. PMID 16860264. doi:10.1016/j.amjopharm.2006.06.006. 
  11. ^ Braestrup C; Squires RF. (1 April 1978). "Pharmacological characterization of benzodiazepine receptors in the brain". Eur J Pharmacol 48 (3): 263–70. PMID 639854. doi:10.1016/0014-2999(78)90085-7. 
  12. ^ Vermeeren A. (2004). "Residual effects of hypnotics: epidemiology and clinical implications". CNS Drugs. 18 (5): 297–328. PMID 15089115. doi:10.2165/00023210-200418050-00003. 
  13. ^ Oelschläger H. (July 4, 1989). "[Chemical and pharmacologic aspects of benzodiazepines]". Schweiz Rundsch Med Prax. 78 (27–28): 766–72. PMID 2570451. 
  14. ^ Lehoullier PF, Ticku MK (March 1987). "Benzodiazepine and beta-carboline modulation of GABA-stimulated 36Cl-influx in cultured spinal cord neurons". Eur. J. Pharmacol. 135 (2): 235–8. PMID 3034628. doi:10.1016/0014-2999(87)90617-0. 
  15. ^ Chan CY; Farb DH (1 September 1985). "Modulation of neurotransmitter action: control of the gamma-aminobutyric acid response through the benzodiazepine receptor" (PDF). J Neurosci 5 (9): 2365–73. PMID 2863335. 
  16. ^ Olive G; Dreux C. (January 1977). "Pharmacologic bases of use of benzodiazepines in peréinatal medicine". Arch Fr Pediatr. 34 (1): 74–89. PMID 851373. 
  17. ^ Griffiths RR, Johnson MW (2005). "Relative abuse liability of hypnotic drugs: a conceptual framework and algorithm for differentiating among compounds". J Clin Psychiatry. 66 Suppl 9: 31–41. PMID 16336040. 
  18. ^ [1][dead link]
  19. ^ Sternbach, L. H.; Archer, G. A.; Earley, J. V.; Fryer, R. I.; Reeder, E.; Wasyliw, N.; Randall, L. O.; Banzger, R. (1965). "Quinazolines and 1,4-Benzodiazepines. XXV.1Structure-Activity Relationships of Aminoalkyl-Substituted 1,4-Benzodiazepin-2-ones". Journal of Medicinal Chemistry 8 (6): 815. PMID 5885077. doi:10.1021/jm00330a019.  edit
  20. ^ G. A. Archer et al., BE 629005  C.A. 60, 15896f (1964).
  21. ^ NL 6401335  C.A. 62, 5289a (1965).
  22. ^ G. A. Archer et al., U.S. Patent 3,299,053 (1967).
  23. ^ R. Fryer, L. H. Sternbach, U.S. Patent 3,567,710 (1971 to Hoffmann-La Roche).
  24. ^ Chemical and Pharmaceutical Bulletin; Vol. 19 (1971) No. 2 P 263-272.

External links