Diazepam

Diazepam
Clinical data
Pronunciation/daɪˈæzɪpæm/ dy-AZ-ip-am
Trade namesValium, others[1]
AHFS/Drugs.comMonograph
MedlinePlusa682047
License data
Pregnancy
category
Dependence
liability		High[3]
Addiction
liability		Moderate[4][5]
Routes of
administration		oral, intramuscular, intravenous, rectal, nasal,[6] buccal film
Drug classBenzodiazepine
ATC code
Legal status
Legal status
  • AU: S4 (Prescription only)[2]
  • BR: Class B1 (Psychoactive drugs)
  • CA: Schedule IV
  • DE: Prescription only (Anlage III for higher doses)
  • NZ: Class C
  • UK: Class C[7][8][9]
  • US: Schedule IV[10][11]
  • UN: Psychotropic Schedule IV
  • In general: ℞ (Prescription only)
Pharmacokinetic data
Bioavailability76% (64–97%) oral, 81% (62–98%) rectal[12]
MetabolismLiver – CYP2B6 (minor route) to desmethyldiazepam, CYP2C19 (major route) to inactive metabolites, CYP3A4 (major route) to temazepam
Metabolites
Elimination half-life(50 h); 20–100 h (32–200 h for main active metabolite desmethyldiazepam)[10][8][9]
ExcretionKidney
Identifiers
IUPAC name
  • 7-chloro-1-methyl-5-phenyl-3H-1,4-benzodiazepin-2-one
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard100.006.476
Chemical and physical data
FormulaC16H13ClN2O
Molar mass284.74 g·mol−1
3D model (JSmol)
SMILES
  • c1ccccc1C2=NCC(=O)N(C)c3ccc(Cl)cc23
InChI
  • InChI=1S/C16H13ClN2O/c1-19-14-8-7-12(17)9-13(14)16(18-10-15(19)20)11-5-3-2-4-6-11/h2-9H,10H2,1H3 Y
  • Key:AAOVKJBEBIDNHE-UHFFFAOYSA-N Y
 NY (what is this?)  (verify)

Diazepam, sold under the brand name Valium among others, is a medicine of the benzodiazepine family that acts as an anxiolytic.[14] It is used to treat a range of conditions, including anxiety, seizures, alcohol withdrawal syndrome, muscle spasms, insomnia, and restless legs syndrome.[14] It may also be used to cause memory loss during certain medical procedures.[15][16] It can be taken orally (by mouth), as a suppository inserted into the rectum, intramuscularly (injected into muscle), intravenously (injection into a vein) or used as a nasal spray.[6][16] When injected intravenously, effects begin in one to five minutes and last up to an hour.[16] When taken by mouth, effects begin after 15 to 60 minutes.[17]

Common side effects include sleepiness and trouble with coordination.[10][16] Serious side effects are rare.[14] They include increased risk of suicide, decreased breathing, and a paradoxical increased risk of seizures if used too frequently in those with epilepsy.[14][16][18] Occasionally, excitement or agitation may occur.[19][20] Long-term use can result in tolerance, dependence, and withdrawal symptoms on dose reduction.[14] Abrupt stopping after long-term use can be potentially dangerous.[14] After stopping, cognitive problems may persist for six months or longer.[19] It is not recommended during pregnancy or breastfeeding.[16] Its mechanism of action works by increasing the effect of the neurotransmitter gamma-aminobutyric acid (GABA).[19]

Diazepam was patented in 1959 by Hoffmann-La Roche.[14][21][22] It has been one of the most frequently prescribed medications in the world since its launch in 1963.[14] In the United States it was the best-selling medication between 1968 and 1982, selling more than 2 billion tablets in 1978 alone.[14] In 2022, it was the 169th most commonly prescribed medication in the United States, with more than 3 million prescriptions.[23][24] In 1985, the patent ended, and there are more than 500 brands available on the market.[14] It is on the World Health Organization's List of Essential Medicines.[25]

  1. ^ Cite error: The named reference auto was invoked but never defined (see the help page).
  2. ^ a b "Valium". NPS MedicineWise. 31 January 2020. Archived from the original on 29 July 2020. Retrieved 9 January 2023.
  3. ^ Edmunds M, Mayhew M (2013). Pharmacology for the Primary Care Provider (4th ed.). Mosby. p. 545. ISBN 978-0-323-08790-2. Archived from the original on 14 January 2023. Retrieved 13 July 2020.
  4. ^ Clinical Addiction Psychiatry. Cambridge University Press. 2010. p. 156. ISBN 978-1-139-49169-3. Archived from the original on 8 September 2017.
  5. ^ Ries RK (2009). Principles of addiction medicine (4 ed.). Philadelphia: Wolters Kluwer/Lippincott Williams & Wilkins. p. 106. ISBN 978-0-7817-7477-2. Archived from the original on 8 September 2017.
  6. ^ a b "Valtoco – diazepam spray". DailyMed. 13 January 2020. Archived from the original on 1 August 2020. Retrieved 13 February 2020.
  7. ^ "Misuse of Drugs Act 1971".
  8. ^ a b "Diazepam Tablets BP 10 mg – Summary of Product Characteristics (SmPC)". (emc). 16 September 2019. Archived from the original on 25 July 2020. Retrieved 25 July 2020.
  9. ^ a b "Diazepam Injection BP Summary of Product Characteristics (SmPC)". emc. 17 January 2022. Archived from the original on 25 January 2023. Retrieved 11 February 2024.
  10. ^ a b c "Valium – diazepam tablet". DailyMed. 8 November 2019. Archived from the original on 28 June 2019. Retrieved 30 December 2019.
  11. ^ "Libervant- diazepam film". DailyMed. 27 April 2024. Retrieved 18 May 2024.
  12. ^ Dhillon S, Oxley J, Richens A (March 1982). "Bioavailability of diazepam after intravenous, oral and rectal administration in adult epileptic patients". British Journal of Clinical Pharmacology. 13 (3): 427–32. doi:10.1111/j.1365-2125.1982.tb01397.x. PMC 1402110. PMID 7059446.
  13. ^ Goodkin HP (2010). "Diazepam". In Panayiotopoulos CP (ed.). Atlas of Epilepsies. London: Springer. pp. 1727–1731. doi:10.1007/978-1-84882-128-6_263. ISBN 978-1-84882-128-6.
  14. ^ a b c d e f g h i j Calcaterra NE, Barrow JC (April 2014). "Classics in chemical neuroscience: diazepam (valium)". ACS Chemical Neuroscience. 5 (4): 253–60. doi:10.1021/cn5000056. PMC 3990949. PMID 24552479.
  15. ^ Cite error: The named reference PubChem was invoked but never defined (see the help page).
  16. ^ a b c d e f "Diazepam". The American Society of Health-System Pharmacists. Archived from the original on 30 June 2015. Retrieved 5 June 2015.
  17. ^ Dhaliwal JS, Saadabadi A (September 2022). "Diazepam". StatPearls [Internet]. StatPearls Publishing. PMID 30725707. Archived from the original on 8 March 2021. Retrieved 13 October 2019.
  18. ^ Dodds TJ (March 2017). "Prescribed Benzodiazepines and Suicide Risk: A Review of the Literature". The Primary Care Companion for CNS Disorders. 19 (2). doi:10.4088/PCC.16r02037. PMID 28257172.
  19. ^ a b c Riss J, Cloyd J, Gates J, Collins S (August 2008). "Benzodiazepines in epilepsy: pharmacology and pharmacokinetics". Acta Neurologica Scandinavica. 118 (2): 69–86. doi:10.1111/j.1600-0404.2008.01004.x. PMID 18384456. S2CID 24453988.
  20. ^ Perkin RM (2008). Pediatric hospital medicine : textbook of inpatient management (2nd ed.). Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins. p. 862. ISBN 978-0-7817-7032-3.
  21. ^ Fischer J, Ganellin CR (2006). Analogue-based Drug Discovery. John Wiley & Sons. p. 535. ISBN 978-3-527-60749-5. Archived from the original on 14 January 2023. Retrieved 5 June 2020.
  22. ^ US patent 3371085, Sternbach LH, Reeder E, "5-ARYL-3H-1,4-BENZODIAZEPIN-2(1H)-ONES", published 27 February 1968, issued 27 February 1968, assigned to Hoffmann La Roche AG 
  23. ^ "The Top 300 of 2022". ClinCalc. Archived from the original on 30 August 2024. Retrieved 30 August 2024.
  24. ^ "Diazepam Drug Usage Statistics, United States, 2013 - 2022". ClinCalc. Retrieved 30 August 2024.
  25. ^ World Health Organization (2023). The selection and use of essential medicines 2023: web annex A: World Health Organization model list of essential medicines: 23rd list (2023). Geneva: World Health Organization. hdl:10665/371090. WHO/MHP/HPS/EML/2023.02.
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