fosazepam

{{Short description|Benzodiazepam}}

{{Infobox drug

| Watchedfields = changed

| verifiedrevid = 455325548

| IUPAC_name = 7-chloro-1-(dimethylphosphorylmethyl)-5-phenyl-3H-1,4-benzodiazepin-2-one

| image = Fosazepam.svg

| width = 190

| tradename =

| legal_status =

| bioavailability =

| metabolism =

| elimination_half-life =

| excretion =

| CAS_number_Ref = {{cascite|correct|??}}

| CAS_number = 35322-07-7

| ATC_prefix = none

| PubChem = 37114

| DrugBank_Ref = {{drugbankcite|correct|drugbank}}

| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}

| ChemSpiderID = 34056

| UNII_Ref = {{fdacite|correct|FDA}}

| UNII = 13AK3H33SG

| KEGG_Ref = {{keggcite|correct|kegg}}

| KEGG = D04248

| C=18 | H=18 | Cl=1 | N=2 | O=2 | P=1

| smiles = ClC1=CC2=C(C=C1)N(CP(C)(C)=O)C(CN=C2C3=CC=CC=C3)=O

| StdInChI_Ref = {{stdinchicite|correct|chemspider}}

| StdInChI = 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

| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}

| StdInChIKey = JMYCGCXYZZHWMO-UHFFFAOYSA-N

}}

FosazepamDE Patent 2022503 is a drug belonging to the benzodiazepine class, which are primarily anti-anxiety and sedative-hypnotic agents. It is a water soluble derivative of diazepam which has been substituted with a dimethylphosphoryl group to improve solubility in water.{{cite journal | vauthors = Nicholson AN, Wright CM | title = Activity of fosazepam, a soluble analogue of diazepam | journal = British Journal of Clinical Pharmacology | volume = 4 | issue = 4 | pages = 494–6 | date = August 1977 | pmid = 409424 | pmc = 1429035 | doi = 10.1111/j.1365-2125.1977.tb00773.x }}{{cite journal | vauthors = Clarke CH, Ferres HM, Nicholson AN, Stone BM | title = Proceedings: Effect of diazepam and a soluble salt of diazepam (fosazepam) on sleep in man | journal = British Journal of Pharmacology | volume = 55 | issue = 2 | pages = 262P | date = October 1975 | pmid = 1201402 | pmc = 1666850 | doi = 10.1111/j.1476-5381.1975.tb07634.x }} At equipotent doses (100 mg fosazepam and 10 mg diazepam), it possesses sedative and anxiolytic properties that are qualitatively and quantitatively similar to the effects of diazepam, with equal sedative-hypnotic, anti-convulsive, and muscle relaxant effects. In comparison to an equipotent dose of nitrazepam (100 mg fosazepam and 10 mg nitrazepam), its effects tended to be of noticeably milder magnitude.{{cite journal | vauthors = Allen S, Oswald I | title = Anxiety and sleep after fosazepam | journal = British Journal of Clinical Pharmacology | volume = 3 | issue = 1 | pages = 165–8 | date = February 1976 | pmid = 184806 | pmc = 1428810 | doi = 10.1111/j.1365-2125.1976.tb00584.x }}

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. 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. 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. Tolerance to the hypnotic effects of fosazepam starts to develop after about 7 days of use.{{cite journal | vauthors = Viukari M, Linnoila M, Aalto U | title = Efficacy and side effects of flurazepam, fosazepam, and nitrazepam as sleeping aids in psychogeriatric patients | journal = Acta Psychiatrica Scandinavica | volume = 57 | issue = 1 | pages = 27–35 | date = January 1978 | pmid = 24980 | doi = 10.1111/j.1600-0447.1978.tb06871.x | s2cid = 23137060 }} Due to the very long elimination half-life of the active metabolite of fosazepam it is not recommended for use as a hypnotic.{{cite journal | vauthors = Breimer DD, Jochemsen R, von Albert HH | title = Pharmacokinetics of benzodiazepines. Short-acting versus long-acting | journal = Arzneimittel-Forschung | volume = 30 | issue = 5a | pages = 875–81 | year = 1980 | pmid = 6106488 }} The main pharmacological effects of fosazepam may be due to its metabolite nordiazepam (desmethyldiazepam), rather than the parent drug. 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.

Fosazepam is of relatively low potency compared to other benzodiazepine derivatives, with a 100 mg dose of fosazepam equivalent to 10 mg of diazepam and 10 mg nitrazepam.{{cite journal | vauthors = Risberg AM, Henricsson S, Ingvar DH | s2cid = 21051544 | title = Evaulation of the effect of fosazepam (a new benzodiazepine), nitrazepam and placebo on sleep patterns in normal subjects | journal = European Journal of Clinical Pharmacology | volume = 12 | issue = 2 | pages = 105–9 | date = October 1977 | pmid = 200435 | doi = 10.1007/BF00645130 }} 60 mg of fosazepam has also been estimated to be equivalent to about 6 mg of diazepam. 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.