Nefazodone

Nefazodone
Clinical data
Trade namesSerzone, Dutonin, Nefadar, others
Other namesBMY-13754-1; MJ-13754-1; MJ-13754; MS-13754
AHFS/Drugs.comMonograph
MedlinePlusa695005
Pregnancy
category
  • C
Routes of
administration		By mouth
ATC code
Legal status
Legal status
  • AU: S4 (Prescription only)
  • BR: Class C1 (Other controlled substances)[1]
  • US: ℞-only
  • In general: ℞ (Prescription only)
Pharmacokinetic data
Bioavailability20% (variable)[2]
Protein binding99% (loosely)[2]
MetabolismLiver (CYP3A4, CYP2D6)[3]
Metabolites• Hydroxynefazodone[2]
• mCPPTooltip meta-Chlorophenylpiperazine[2]
• p-Hydroxynefazodone[3]
• Triazoledione[2]
Elimination half-life• Nefazodone: 2–4 hours[2]
• Hydroxynefazodone: 1.5–4 hours[2]
• Triazoledione: 18 hours[2]
• mCPPTooltip meta-Chlorophenylpiperazine: 4–8 hours[2]
ExcretionUrine: 55%
Feces: 20–30%
Identifiers
  • 1-(3-[4-(3-chlorophenyl)piperazin-1-yl]propyl)-3-ethyl-4-(2-phenoxyethyl)-1H-1,2,4-triazol-5(4H)-one
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
Chemical and physical data
FormulaC25H32ClN5O2
Molar mass470.01 g·mol−1
3D model (JSmol)
  • Clc4cccc(N3CCN(CCCN1/N=C(\N(C1=O)CCOc2ccccc2)CC)CC3)c4
  • InChI=1S/C25H32ClN5O2/c1-2-24-27-31(25(32)30(24)18-19-33-23-10-4-3-5-11-23)13-7-12-28-14-16-29(17-15-28)22-9-6-8-21(26)20-22/h3-6,8-11,20H,2,7,12-19H2,1H3 checkY
  • Key:VRBKIVRKKCLPHA-UHFFFAOYSA-N checkY
  (verify)

Nefazodone, sold formerly under the brand names Serzone, Dutonin, and Nefadar among others, is an atypical antidepressant medication which is used in the treatment of depression and for other uses.[4][5][6][7] Nefazodone is still available in the United States,[8] but was withdrawn from other countries due to rare liver toxicity. The medication is taken by mouth.[9]

Side effects of nefazodone include dry mouth, sleepiness, nausea, dizziness, blurred vision, weakness, lightheadedness, confusion, and postural low blood pressure, among others.[9] Rarely, nefazodone can cause serious liver damage, with an incidence of death or liver transplantation of about 1 in every 250,000 to 300,000 patient years.[9] Nefazodone is a phenylpiperazine compound and is related to trazodone. It has been described as a serotonin antagonist and reuptake inhibitor (SARI) due to its combined actions as a potent antagonist of the serotonin 5-HT2A and 5-HT2C receptors and weak serotonin–norepinephrine–dopamine reuptake inhibitor (SNDRI).

Nefazodone was introduced for medical use in 1994.[7][10][11] Generic versions were introduced in 2003.[12] Serious liver toxicity was first reported with nefazodone in 1998, and it was withdrawn from most markets by 2004.[11][13] However, as of 2023, it continues to be available in the United States in generic from one manufacturer, Teva Pharmaceuticals[14] and is manufactured in Israel.[15]

  1. ^ Anvisa (2023-03-31). "RDC Nº 784 - Listas de Substâncias Entorpecentes, Psicotrópicas, Precursoras e Outras sob Controle Especial" [Collegiate Board Resolution No. 784 - Lists of Narcotic, Psychotropic, Precursor, and Other Substances under Special Control] (in Brazilian Portuguese). Diário Oficial da União (published 2023-04-04). Archived from the original on 2023-08-03. Retrieved 2023-08-16.
  2. ^ a b c d e f g h i Schatzberg AF, Nemeroff CB (2017). The American Psychiatric Association Publishing Textbook of Psychopharmacology, Fifth Edition. American Psychiatric Pub. pp. 460–. ISBN 978-1-58562-523-9.
  3. ^ a b Pacifici GM, Pelkonen O (24 May 2001). Interindividual Variability in Human Drug Metabolism. CRC Press. pp. 103–. ISBN 978-0-7484-0864-1.
  4. ^ Cite error: The named reference Elks2014 was invoked but never defined (see the help page).
  5. ^ Cite error: The named reference IndexNominum2000 was invoked but never defined (see the help page).
  6. ^ Cite error: The named reference Drugs.com was invoked but never defined (see the help page).
  7. ^ a b "Drugs of Current Interest: Nefazodone". WHO Pharmaceuticals Newsletter (1). 2003. Archived from the original on April 3, 2015.
  8. ^ Cite error: The named reference Teva Nefazodone Statement was invoked but never defined (see the help page).
  9. ^ a b c "Serzone (Nefazodone): Side Effects, Interactions, Warning, Dosage & Uses". RxList. January 2005. Archived from the original on 6 June 2017. Retrieved 3 June 2017.
  10. ^ Cite error: The named reference pmid8748566 was invoked but never defined (see the help page).
  11. ^ a b Babai S, Auclert L, Le-Louët H (2021). "Safety data and withdrawal of hepatotoxic drugs". Therapie. 76 (6): 715–723. doi:10.1016/j.therap.2018.02.004. PMID 29609830.
  12. ^ "Nefazodone". Drug Patent Watch. Archived from the original on 27 January 2018. Retrieved 3 June 2017.
  13. ^ Cite error: The named reference CBS2004 was invoked but never defined (see the help page).
  14. ^ "Drugs@FDA: FDA-Approved Drugs". Archived from the original on 2021-08-27. Retrieved 2023-02-11.
  15. ^ "DailyMed - NEFAZODONE HYDROCHLORIDE tablet". dailymed.nlm.nih.gov. Archived from the original on 2016-09-16. Retrieved 2023-10-29.