Fosazepam

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Fosazepam
Fosazepam.svg
Clinical data
ATC code
  • none
Identifiers
  • 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
Formula C18H18ClN2O2P
Molar mass 360.78 g·mol−1
3D model (JSmol)
  • ClC1=CC2=C(C=C1)N(CP(C)(C)=O)C(CN=C2C3=CC=CC=C3)=O
  • 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 Yes check.svgY
  • Key:JMYCGCXYZZHWMO-UHFFFAOYSA-N Yes check.svgY
   (verify)

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 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

Related Research Articles

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Diazepam, first marketed as Valium, is a medicine of the benzodiazepine family that acts as an anxiolytic. It is commonly used to treat a range of conditions, including anxiety, seizures, alcohol withdrawal syndrome, benzodiazepine withdrawal syndrome, muscle spasms, insomnia, and restless legs syndrome. It may also be used to cause memory loss during certain medical procedures. It can be taken by mouth, inserted into the rectum, injected into muscle, injected into a vein or used as a nasal spray. When given into a vein, effects begin in one to five minutes and last up to an hour. By mouth, effects begin after 15 to 60 minutes.

Temazepam Insomnia medication

Temazepam is a medication used to treat insomnia. Such use should generally be for less than ten days. It is taken by mouth. Effects generally begin within an hour and last for up to eight hours.

Nitrazepam Benzodiazepine sedative

Nitrazepam, sold under the brand name Mogadon among others, is a hypnotic drug of the benzodiazepine class used for short-term relief from severe, disabling anxiety and insomnia. It also has sedative (calming) properties, as well as amnestic, anticonvulsant, and skeletal muscle relaxant effects.

Bromazepam Benzodiazepine drug

Bromazepam, sold under many brand names, is a benzodiazepine. It is mainly an anti-anxiety agent with similar side effects to diazepam (Valium). In addition to being used to treat anxiety or panic states, bromazepam may be used as a premedicant prior to minor surgery. Bromazepam typically comes in doses of 3 mg and 6 mg tablets.

Flurazepam Hypnotic medication

Flurazepam is a drug which is a benzodiazepine derivative. It possesses anxiolytic, anticonvulsant, hypnotic, sedative and skeletal muscle relaxant properties. It produces a metabolite with a long half-life, which may stay in the bloodstream for days. Flurazepam was patented in 1968 and came into medical use the same year. Flurazepam, developed by Roche Pharmaceuticals was one of the first benzo hypnotics to be marketed.

Clobazam Benzodiazepine class medication

Clobazam, sold under the brand names Frisium, Onfi and others, is a benzodiazepine class medication that was patented in 1968. Clobazam was first synthesized in 1966 and first published in 1969. Clobazam was originally marketed as an anxioselective anxiolytic since 1970, and an anticonvulsant since 1984. The primary drug-development goal was to provide greater anxiolytic, anti-obsessive efficacy with fewer benzodiazepine-related side effects.

Quazepam Benzodiazipine

Quazepam is a relatively long-acting benzodiazepine derivative drug developed by the Schering Corporation in the 1970s. Quazepam is indicated for the treatment of insomnia including sleep induction and sleep maintenance. Quazepam induces impairment of motor function and has relatively selective hypnotic and anticonvulsant properties with considerably less overdose potential than other benzodiazepines. Quazepam is an effective hypnotic which induces and maintains sleep without disruption of the sleep architecture.

Nordazepam

Nordazepam is a 1,4-benzodiazepine derivative. Like other benzodiazepine derivatives, it has amnesic, anticonvulsant, anxiolytic, muscle relaxant, and sedative properties. However, it is used primarily in the treatment of anxiety disorders. It is an active metabolite of diazepam, chlordiazepoxide, clorazepate, prazepam, pinazepam, and medazepam.

Clorazepate Benzodiazepine medication

Clorazepate, sold under the brand name Tranxene among others, is a benzodiazepine medication. It possesses anxiolytic, anticonvulsant, sedative, hypnotic, and skeletal muscle relaxant properties. Clorazepate is an unusually long-lasting benzodiazepine and serves as a majoritive prodrug for the equally long-lasting desmethyldiazepam, which is rapidly produced as an active metabolite. Desmethyldiazepam is responsible for most of the therapeutic effects of clorazepate.

Loprazolam Benzodiazepine

Loprazolam (triazulenone) marketed under many brand names is a benzodiazepine medication. It possesses anxiolytic, anticonvulsant, hypnotic, sedative and skeletal muscle relaxant properties. It is licensed and marketed for the short-term treatment of moderately-severe insomnia.

Pinazepam

Pinazepam is a benzodiazepine drug. It possesses anxiolytic, anticonvulsant, sedative and skeletal muscle relaxant properties.

Camazepam

Camazepam is a benzodiazepine psychoactive drug, marketed under the brand names Albego, Limpidon and Paxor. It is the dimethyl carbamate ester of temazepam, a metabolite of diazepam. While it possesses anxiolytic, anticonvulsant, skeletal muscle relaxant and hypnotic properties it differs from other benzodiazepines in that its anxiolytic properties are particularly prominent but has comparatively limited anticonvulsant, hypnotic and skeletal muscle relaxant properties.

Lormetazepam Benzodiazepine

Lormetazepam, sold under the brand name Noctamid among others, is a drug which is a short to intermediate acting 3-hydroxy benzodiazepine derivative and temazepam analogue. It possesses hypnotic, anxiolytic, anticonvulsant, sedative, and skeletal muscle relaxant properties.

Brotizolam Benzodiazipine

Brotizolam is a sedative-hypnotic thienotriazolodiazepine drug which is a benzodiazepine analog. It possesses anxiolytic, anticonvulsant, hypnotic, sedative and skeletal muscle relaxant properties, and is considered to be similar in effect to other short-acting hypnotic benzodiazepines such as triazolam or midazolam. It is used in the short-term treatment of severe insomnia. Brotizolam is a highly potent and short-acting hypnotic, with a typical dose ranging from 0.125 to 0.25 milligrams, which is rapidly eliminated with an average half-life of 4.4 hours.

Bretazenil

Bretazenil (Ro16-6028) is an imidazopyrrolobenzodiazepine anxiolytic drug which is derived from the benzodiazepine family, and was invented in 1988. It is most closely related in structure to the GABA antagonist flumazenil, although its effects are somewhat different. It is classified as a high-potency benzodiazepine due to its high affinity binding to benzodiazepine binding sites where it acts as a partial agonist. Its profile as a partial agonist and preclinical trial data suggests that it may have a reduced adverse effect profile. In particular bretazenil has been proposed to cause a less strong development of tolerance and withdrawal syndrome. Bretazenil differs from traditional 1,4-benzodiazepines by being a partial agonist and because it binds to α1, α2, α3, α4, α5 and α6 subunit containing GABAA receptor benzodiazepine receptor complexes. 1,4-benzodiazepines bind only to α1, α2, α3 and α5GABAA benzodiazepine receptor complexes.

Chlordiazepoxide Benzodiazepine class sedative and hypnotic medication

Chlordiazepoxide, trade name Librium among others, is a sedative and hypnotic medication of the benzodiazepine class; it is used to treat anxiety, insomnia and symptoms of withdrawal from alcohol and other drugs.

Delorazepam

Delorazepam, also known as chlordesmethyldiazepam and nordiclazepam, is a drug which is a benzodiazepine and a derivative of desmethyldiazepam. It is marketed in Italy, where it is available under the trade name EN and Dadumir. Delorazepam (chlordesmethyldiazepam) is also an active metabolite of the benzodiazepine drugs diclazepam and cloxazolam. Adverse effects may include hangover type effects, drowsiness, behavioural impairments and short-term memory impairments. Similar to other benzodiazepines delorazepam has anxiolytic, skeletal muscle relaxant, hypnotic and anticonvulsant properties.

Benzoctamine

Benzoctamine is a drug that possesses sedative and anxiolytic properties. Marketed as Tacitin by Ciba-Geigy, it is different from most sedative drugs because in most clinical trials it does not produce respiratory depression, but actually stimulates the respiratory system. As a result, when compared to other sedative and anxiolytic drugs such as benzodiazepines like diazepam, it is a safer form of tranquilizing. However, when co-administered with other drugs that cause respiratory depression, like morphine, it can cause increased respiratory depression.

Suriclone

Suriclone (Suril) is a sedative and anxiolytic drug in the cyclopyrrolone family of drugs. Other cyclopyrrolone drugs include zopiclone and pagoclone.

Premazepam

Premazepam is a benzodiazepine derivative. It is a partial agonist of benzodiazepine receptors and was shown in 1984 to possess both anxiolytic and sedative properties in humans but was never marketed.

References

  1. DE Patent 2022503
  2. 1 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. 1 2 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. 1 2 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. 1 2 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.