Nefazodone (CHEM002355)

IdentificationTaxonomyBiological PropertiesPhysical PropertiesToxicity ProfileSpectraConcentrationsLinksReferencesTargets (14)XML
Record Information
Version1.0
Creation Date2009-07-21 20:28:27 UTC
Update Date2026-05-14 16:58:14 UTC
Accession NumberCHEM002355
Identification
Common NameNefazodone
ClassSmall Molecule
DescriptionNefazodone hydrochloride (trade name Serzone) is an antidepressant drug marketed by Bristol-Myers Squibb. Its sale was discontinued in 2003 in some countries, due to the small possibility of hepatic (liver) injury, which could lead to the need for a liver transplant, or even death. The incidence of severe liver damage is approximately 1 in 250,000 to 300,000 patient-years. On May 20, 2004, Bristol-Myers Squibb discontinued the sale of Serzone in the United States. [Wikipedia]
Contaminant Sources
  • HMDB Contaminants - Urine
  • STOFF IDENT Compounds
  • T3DB toxins
Contaminant Type
  • Amine
  • Analgesic
  • Antidepressant
  • Antidepressant, Second-Generation
  • Antidepressive Agent
  • Antidepressive Agent, Second-Generation
  • Drug
  • Ether
  • Human Neurotoxin
  • Metabolite
  • Organic Compound
  • Organochloride
  • Serotonin Agent
  • Synthetic Compound
Chemical Structure
Thumb
MOLSDFPDBSMILESInChI
Synonyms
ValueSource
1-(3-(4-(m-Chlorophenyl)-1-piperazinyl)propyl)-3-ethyl-4-(2-phenoxyethyl)-delta2-1,2,4-triazolin-5-oneChEBI
NefazodonaChEBI
NefazodonumChEBI
1-(3-(4-(m-Chlorophenyl)-1-piperazinyl)propyl)-3-ethyl-4-(2-phenoxyethyl)-δ2-1,2,4-triazolin-5-oneGenerator
Bristol-myers squibb brand OF nefazodone hydrochlorideHMDB
DutoninHMDB
RulivanHMDB
Apo-nefazodoneHMDB
Apotex brand OF nefazodone hydrochlorideHMDB
Hormosan brand OF nefazodone hydrochlorideHMDB
Linson pharma brand OF nefazodone hydrochlorideHMDB
NefadarHMDB
Lin-nefazodoneHMDB
SerzoneHMDB
Bristol-myers brand OF nefazodone hydrochlorideHMDB
Europharma brand OF nefazodone hydrochlorideHMDB
Menarini brand OF nefazodone hydrochlorideHMDB
MenfazonaHMDB
Nefazodone hydrochlorideHMDB
Chemical FormulaC25H32ClN5O2
Average Molecular Mass470.007 g/mol
Monoisotopic Mass469.224 g/mol
CAS Registry Number83366-66-9
IUPAC Name1-{3-[4-(3-chlorophenyl)piperazin-1-yl]propyl}-3-ethyl-4-(2-phenoxyethyl)-4,5-dihydro-1H-1,2,4-triazol-5-one
Traditional Namenefazodone
SMILESCCC1=NN(CCCN2CCN(CC2)C2=CC(Cl)=CC=C2)C(=O)N1CCOC1=CC=CC=C1
InChI IdentifierInChI=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
InChI KeyVRBKIVRKKCLPHA-UHFFFAOYSA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as phenylpiperazines. Phenylpiperazines are compounds containing a phenylpiperazine skeleton, which consists of a piperazine bound to a phenyl group.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassDiazinanes
Sub ClassPiperazines
Direct ParentPhenylpiperazines
Alternative Parents
Substituents
  • Phenylpiperazine
  • N-arylpiperazine
  • Phenol ether
  • Tertiary aliphatic/aromatic amine
  • Phenoxy compound
  • Dialkylarylamine
  • Aniline or substituted anilines
  • Chlorobenzene
  • N-alkylpiperazine
  • Halobenzene
  • Alkyl aryl ether
  • Monocyclic benzene moiety
  • Aryl halide
  • Aryl chloride
  • Benzenoid
  • Heteroaromatic compound
  • Azole
  • 1,2,4-triazole
  • Tertiary aliphatic amine
  • Tertiary amine
  • Ether
  • Azacycle
  • Organooxygen compound
  • Organonitrogen compound
  • Organochloride
  • Organohalogen compound
  • Organic oxide
  • Organopnictogen compound
  • Organic oxygen compound
  • Hydrocarbon derivative
  • Organic nitrogen compound
  • Amine
  • Aromatic heteromonocyclic compound
Molecular FrameworkAromatic heteromonocyclic compounds
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Membrane
Biofluid LocationsNot Available
Tissue LocationsNot Available
PathwaysNot Available
Applications
Biological Roles
Chemical RolesNot Available
Physical Properties
StateSolid
AppearanceWhite powder.
Experimental Properties
PropertyValue
Melting Point83.5°C
Boiling PointNot Available
Solubility6.98e-02 g/L
Predicted Properties
PropertyValueSource
Water Solubility0.07 g/LALOGPS
logP3.71ALOGPS
logP4.65ChemAxon
logS-3.8ALOGPS
pKa (Strongest Basic)7.09ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area51.62 ŲChemAxon
Rotatable Bond Count10ChemAxon
Refractivity132.38 m³·mol⁻¹ChemAxon
Polarizability51.85 ųChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash KeyView
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-08fv-6496100000-3f42082c30f022624e00Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, PositiveNot AvailableSpectrum
LC-MS/MSLC-MS/MS Spectrum - , positivesplash10-00di-0260900000-3ebf8f0b9eda5fea1378Spectrum
LC-MS/MSLC-MS/MS Spectrum - , positivesplash10-00di-3790200000-9f64b1295a633dcdd772Spectrum
LC-MS/MSLC-MS/MS Spectrum - 35V, Positivesplash10-00di-0190600000-e660a26f2b5417360e81Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-00di-0152900000-340890a453c0a56c76b3Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0fbl-4695100000-93bef331c390dbfee2d6Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-01pd-7940000000-d9eeb95454a6d048ce65Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-016r-3931500000-a506620891ae02e35e82Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-002f-9730100000-83a513c505af8bed8b82Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0006-9200000000-522fe62ba68195d5d1b2Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-00di-1200900000-c3db8beb65c2741f9ab9Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-00dr-2359600000-4969e962cd4b5264e810Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-002s-1981100000-c2114e4725584e3d862aSpectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-0007-6805900000-806a5c4806b242b95249Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0006-9014200000-f95736b782384e65b6cfSpectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0006-9000000000-37e7f69fd131b8f395ddSpectrum
MSMass Spectrum (Electron Ionization)splash10-0uk9-9846000000-49cb6e97c09a9e806dd5Spectrum
Toxicity Profile
Route of ExposureNefazodone is rapidly and completely absorbed. Its absolute bioavailability is low (about 20%).
Mechanism of ToxicityWithin the serotonergic system, nefazodone acts as an antagonist at type 2 serotonin (5-HT2) post-synaptic receptors and, like fluoxetine-type antidepressants, inhibits pre-synaptic serotonin (5-HT) reuptake. These mechanisms increase the amount of serotonin available to interact with 5-HT receptors. Within the noradrenergic system, nefazodone inhibits norepinephrine uptake minimally. Nefazodone also antagonizes alpha(1)-adrenergic receptors, producing sedation, muscle relaxation, and a variety of cardiovascular effects. Nefazodone's affinity for benzodiazepine, cholinergic, dopaminergic, histaminic, and beta or alpha(2)-adrenergic receptors is not significant.
MetabolismHepatic. Route of Elimination: Nefazodone is extensively metabolized after oral administration by n-dealkylation and aliphatic and aromatic hydroxylation, and less than 1% of administered nefazodone is excreted unchanged in urine. Half Life: 2-4 hours
Toxicity ValuesNot Available
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesNefazodone (sold as Serzone, Nefadar) is a psychoactive drug and antidepressant. [wikipedia]
Minimum Risk LevelNot Available
Health EffectsSerious side effects include an allergic reaction, fainting, or painful/prolonged erection. [Wikipedia]
SymptomsCases of life-threatening hepatic failure have been reported in patients treated with nefazodone.
TreatmentTreatment should consist of those general measures employed in the management of overdosage with any antidepressant. Ensure an adequate airway, oxygenation, and ventilation. Monitor cardiac rhythm and vital signs. General supportive and symptomatic measures are also recommended. Induction of emesis is not recommended. Gastric lavage with a large-bore orogastric tube with appropriate airway protection, if needed, may be indicated if performed soon after ingestion, or in symptomatic patients. Activated charcoal should be administered. Due to the wide distribution of nefazodone in body tissues, forced diuresis, dialysis, hemoperfusion, and exchange transfusion are unlikely to be of benefit. No specific antidotes for nefazodone are known. (3)
Concentrations
Not Available
DrugBank IDDB01149
HMDB IDHMDB0015280
FooDB IDNot Available
Phenol Explorer IDNot Available
KNApSAcK IDNot Available
BiGG IDNot Available
BioCyc IDNot Available
METLIN IDNot Available
PDB IDNot Available
Wikipedia LinkNefazodone
Chemspider ID4294
ChEBI ID7494
PubChem Compound ID4449
Kegg Compound IDC07256
YMDB IDNot Available
ECMDB IDNot Available
References
Synthesis Reference

DrugSyn.org

MSDSNot Available
General References
1. Davis R, Whittington R, Bryson HM: Nefazodone. A review of its pharmacology and clinical efficacy in the management of major depression. Drugs. 1997 Apr;53(4):608-36.