Fosazepam

Fosazepam[1] is a drug which is a benzodiazepine derivative; it is a water soluble derivative 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
Clinical data
ATC code
  • none
Identifiers
IUPAC name
  • 7-chloro-1-(dimethylphosphorylmethyl)-5-phenyl-3H-1,4-benzodiazepin-2-one
CAS Number
PubChem CID
ChemSpider
UNII
KEGG
CompTox Dashboard (EPA)
Chemical and physical data
FormulaC18H18ClN2O2P
Molar mass360.78 g·mol−1
3D model (JSmol)
SMILES
  • ClC1=CC2=C(C=C1)N(CP(C)(C)=O)C(CN=C2C3=CC=CC=C3)=O
InChI
  • InChI=1S/C18H18ClN2O2P/c1-24(2,23)12-21-16-9-8-14(19)10-15(16)18(20-11-17(21)22)13-6-4-3-5-7-13/h3-10H,11-12H2,1-2H3 Y
  • Key:JMYCGCXYZZHWMO-UHFFFAOYSA-N Y
  (verify)

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

References
  1. DE Patent 2022503
  2. Clarke CH, Ferres HM, Nicholson AN, Stone BM (October 1975). "Proceedings: Effect of diazepam and a soluble salt of diazepam (fosazepam) on sleep in man". British Journal of Pharmacology. 55 (2): 262P. doi:10.1111/j.1476-5381.1975.tb07634.x. PMC 1666850. PMID 1201402.
  3. Allen S, Oswald I (February 1976). "Anxiety and sleep after fosazepam". British Journal of Clinical Pharmacology. 3 (1): 165–8. doi:10.1111/j.1365-2125.1976.tb00584.x. PMC 1428810. PMID 184806.
  4. Nicholson AN, Wright CM (August 1977). "Activity of fosazepam, a soluble analogue of diazepam". British Journal of Clinical Pharmacology. 4 (4): 494–6. doi:10.1111/j.1365-2125.1977.tb00773.x. PMC 1429035. PMID 409424.
  5. Risberg AM, Henricsson S, Ingvar DH (October 1977). "Evaulation of the effect of fosazepam (a new benzodiazepine), nitrazepam and placebo on sleep patterns in normal subjects". European Journal of Clinical Pharmacology. 12 (2): 105–9. doi:10.1007/BF00645130. PMID 200435. S2CID 21051544.
  6. 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. doi:10.1111/j.1600-0447.1978.tb06871.x. PMID 24980. S2CID 23137060.
  7. Breimer DD, Jochemsen R, von Albert HH (1980). "Pharmacokinetics of benzodiazepines. Short-acting versus long-acting". Arzneimittel-Forschung. 30 (5a): 875–81. PMID 6106488.
  8. Nicholson AN, Wright CM (August 1977). "Activity of fosazepam, a soluble analogue of diazepam". British Journal of Clinical Pharmacology. 4 (4): 494–6. doi:10.1111/j.1365-2125.1977.tb00773.x. PMC 1429035. PMID 409424.
  9. 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. doi:10.1111/j.1600-0447.1978.tb06871.x. PMID 24980. S2CID 23137060.
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