Fosazepam

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Fosazepam
Fosazepam.svg
Systematic (IUPAC) name
7-chloro-1-(dimethylphosphorylmethyl)-5-phenyl-3H-1,4-benzodiazepin-2-one
Clinical data
Legal status
?
Identifiers
CAS number 35322-07-7 YesY
ATC code None
PubChem CID 37114
ChemSpider 34056 YesY
UNII 13AK3H33SG YesY
KEGG D04248 YesY
Chemical data
Formula C18H18ClN2O2P 
Mol. mass 360.774
 YesY (what is this?)  (verify)

Fosazepam[1] is a drug which is a benzodiazepine derivative; it is a water soluble salt of diazepam.[2] It has sedative and anxiolytic effects,[3] and is a derivative of diazepam which has been substituted with a dimethylphosphoryl group to improve solubility in water.[4]

Fosazepam has similar effects on sleep as other benzodiazepines. In a clinical trial it was reported that fosazepam to lead to increased sleep duration with less broken sleep but sleep quality was worsened with suppressed deep sleep and increased light sleep. Adverse effects included feelings of impaired morning vitality and upon discontinuing the drug benzodiazepine withdrawal symptoms of anxiety, impaired concentration and impaired morning vitality were experienced.[3] Another clinical trial also found worsening of sleep while on benzodiazepines as well as during withdrawal with suppression of deep sleep stages including REM sleep, with increased light sleep upon withdrawal.[5] The main metabolites of fosazepam are 3-hydroxyfosazepam and the active metabolite desmethyldiazepam which has a very long elimination half-life of about 3 days.[3] Tolerance to the hypnotic effects of fosazepam starts to develop after about 7 days of use.[6] Due to the very long elimination half-life of the active metabolite of fosazepam it is not recommended for use as a hypnotic.[7] The main pharmacological effects of fosazepam may be due to its metabolite nordiazepam (desmethyldiazepam), rather than the parent drug.[8] The long-acting active metabolite nordazepam can cause extended sedative effects at high doses or with prolonged use, and may produce residual sedation upon awakening.[7]

Fosazepam is of relatively low potency compared to other benzodiazepine derivatives, with a 100 mg dose of fosazepam equivalent to 10 mg of nitrazepam.[5] 60 mg of fosazepam has also been estimated to be equivalent to about 5 – 10 mg of diazepam.[2] Fosazepam has similar effects to nitrazepam, but with a shorter duration of action and less tendency to cause over sedation, motor-impairment, amnesia, rebound insomnia, and morning grogginess.[9]

See also[edit]

References[edit]

  1. ^ DE Patent 2022503
  2. ^ a b Clarke, CH.; Ferres, HM.; Nicholson, AN.; Stone, BM. (Oct 1975). "Proceedings: Effect of diazepam and a soluble salt of diazepam (fosazepam) on sleep in man". Br J Pharmacol 55 (2): 262P. PMC 1666850. PMID 1201402. 
  3. ^ a b c Allen, S.; Oswald, I. (Feb 1976). "Anxiety and sleep after fosazepam". Br J Clin Pharmacol 3 (1): 165–8. doi:10.1111/j.1365-2125.1976.tb00584.x. PMC 1428810. PMID 184806. 
  4. ^ Nicholson AN, Wright CM. Activity of fosazepam, a soluble analogue of diazepam. British Journal of Clinical Pharmacology. 1977 Aug;4(4):494-6.
  5. ^ a b Risberg, AM.; Henricsson, S.; Ingvar, DH. (Oct 1977). "Evaulation of the effect of fosazepam (a new benzodiazepine), nitrazepam and placebo on sleep patterns in normal subjects". Eur J Clin Pharmacol 12 (2): 105–9. doi:10.1007/BF00645130. PMID 200435. 
  6. ^ Viukari, M.; Linnoila, M.; Aalto, U. (Jan 1978). "Efficacy and side effects of flurazepam, fosazepam, and nitrazepam as sleeping aids in psychogeriatric patients". Acta Psychiatr Scand 57 (1): 27–35. doi:10.1111/j.1600-0447.1978.tb06871.x. PMID 24980. 
  7. ^ a b Breimer, DD.; Jochemsen, R.; von Albert, HH. (1980). "Pharmacokinetics of benzodiazepines. Short-acting versus long-acting". Arzneimittelforschung 30 (5a): 875–81. PMID 6106488. 
  8. ^ Nicholson, AN.; Wright, CM. (Aug 1977). "Activity of fosazepam, a soluble analogue of diazepam". Br J Clin Pharmacol 4 (4): 494–6. doi:10.1111/j.1365-2125.1977.tb00773.x. PMC 1429035. PMID 409424. 
  9. ^ Viukari M, Linnoila M, Aalto U. Efficacy and side effects of flurazepam, fosazepam, and nitrazepam as sleeping aids in psychogeriatric patients. Acta Psychiatrica Scandinavica. 1978 Jan;57(1):27-35.