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Details

Stereochemistry ACHIRAL
Molecular Formula C25H32ClN5O2.ClH
Molecular Weight 506.468
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of NEFAZODONE HYDROCHLORIDE

SMILES

Cl.CCC1=NN(CCCN2CCN(CC2)C3=CC=CC(Cl)=C3)C(=O)N1CCOC4=CC=CC=C4

InChI

InChIKey=DYCKFEBIOUQECE-UHFFFAOYSA-N
InChI=1S/C25H32ClN5O2.ClH/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;1H

HIDE SMILES / InChI

Description
Curator's Comment: Description was created based on several sources, including https://www.drugs.com/pro/nefazodone.html

Nefazodone 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. Within 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.

CNS Activity

Curator's Comment: antidepressant

Originator

Curator's Comment: # Bristol-Myers Squibb

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
5.8 nM [Ki]
290.0 nM [Ki]
5.5 nM [Ki]
84.0 nM [Ki]
52.0 nM [Ki]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
NEFAZODONE HYDROCHLORIDE

Approved Use

Nefazodone hydrochloride tablets are indicated for the treatment of depression. When deciding among the alternative treatments available for this condition, the prescriber should consider the risk of hepatic failure associated with Nefazodone hydrochloride treatment. In many cases, this would lead to the conclusion that other drugs should be tried first.

Launch Date

2003
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
880 μg/L
100 mg 2 times / day steady-state, oral
dose: 100 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
NEFAZODONE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
276 μg/L
100 mg single, oral
dose: 100 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
NEFAZODONE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
415 ng/mL
200 mg single, oral
dose: 200 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
NEFAZODONE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: FASTED
1588 ng/mL
200 mg 2 times / day steady-state, oral
dose: 200 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
NEFAZODONE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: FASTED
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
3213 μg × h/L
100 mg 2 times / day steady-state, oral
dose: 100 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
NEFAZODONE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
787 μg × h/L
100 mg single, oral
dose: 100 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
NEFAZODONE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
1220 ng × h/mL
200 mg single, oral
dose: 200 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
NEFAZODONE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: FASTED
6378 ng × h/mL
200 mg 2 times / day steady-state, oral
dose: 200 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
NEFAZODONE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: FASTED
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
7 h
100 mg 2 times / day steady-state, oral
dose: 100 mg
route of administration: Oral
experiment type: STEADY-STATE
co-administered:
NEFAZODONE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
5.7 h
100 mg single, oral
dose: 100 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
NEFAZODONE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: FEMALE / MALE
food status: FASTED
5.2 h
200 mg single, oral
dose: 200 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
NEFAZODONE plasma
Homo sapiens
population: HEALTHY
age: ADULT
sex: UNKNOWN
food status: FASTED
Doses

Doses

DosePopulationAdverse events​
200 mg single, oral
Highest studied dose
Dose: 200 mg
Route: oral
Route: single
Dose: 200 mg
Sources:
unhealthy, adult
Health Status: unhealthy
Age Group: adult
Sex: unknown
Sources:
Other AEs: Nausea and vomiting...
Other AEs:
Nausea and vomiting
Sources:
200 mg single, oral
Highest studied dose
Dose: 200 mg
Route: oral
Route: single
Dose: 200 mg
Sources:
unhealthy, adult
Health Status: unhealthy
Age Group: adult
Sex: unknown
Sources:
Other AEs: Nausea and vomiting...
Other AEs:
Nausea and vomiting
Sources:
430 mg 1 times / day steady, oral
Highest studied dose
Dose: 430 mg, 1 times / day
Route: oral
Route: steady
Dose: 430 mg, 1 times / day
Sources:
unhealthy, adult
Health Status: unhealthy
Age Group: adult
Sex: M
Sources:
Other AEs: Headaches, Dry mouth...
Other AEs:
Headaches (53%)
Dry mouth (42%)
Diarrhea (42%)
Sources:
600 mg 1 times / day steady, oral
Highest studied dose
Dose: 600 mg, 1 times / day
Route: oral
Route: steady
Dose: 600 mg, 1 times / day
Sources:
unhealthy, adult
Health Status: unhealthy
Age Group: adult
Sex: unknown
Sources:
Other AEs: Somnolence...
Other AEs:
Somnolence (25%)
Sources:
600 mg 1 times / day steady, oral
Highest studied dose
Dose: 600 mg, 1 times / day
Route: oral
Route: steady
Dose: 600 mg, 1 times / day
Sources:
unhealthy, adult
Health Status: unhealthy
Age Group: adult
Sex: unknown
Sources:
Other AEs: Dry mouth, Nausea...
Other AEs:
Dry mouth (25%)
Nausea (22%)
Dizziness (17%)
Constipation (14%)
Asthenia (11%)
Light headedness (10%)
Blurred vision (9%)
Confusion (7%)
Abnormal vision (7%)
Sources:
600 mg 1 times / day steady, oral
Highest studied dose
Dose: 600 mg, 1 times / day
Route: oral
Route: steady
Dose: 600 mg, 1 times / day
Sources:
unhealthy, adult
Health Status: unhealthy
Age Group: adult
Sex: unknown
Sources:
Disc. AE: Nausea, Headache...
AEs leading to
discontinuation/dose reduction:
Nausea (3.5%)
Headache (2.9%)
Dizziness (1.9%)
Somnolence (1.5%)
Insomnia (1.5%)
Asthenia (1.3%)
Agitation (1.2%)
Sources:
200 mg single, oral
Highest studied dose
Dose: 200 mg
Route: oral
Route: single
Dose: 200 mg
Sources:
healthy, elderly
Health Status: healthy
Age Group: elderly
Sex: unknown
Sources:
Other AEs: Nausea and vomiting...
Other AEs:
Nausea and vomiting
Sources:
200 mg single, oral
Highest studied dose
Dose: 200 mg
Route: oral
Route: single
Dose: 200 mg
Sources:
healthy, younger
Health Status: healthy
Age Group: younger
Sex: unknown
Sources:
Other AEs: Nausea and vomiting...
Other AEs:
Nausea and vomiting
Sources:
AEs

AEs

AESignificanceDosePopulation
Nausea and vomiting
200 mg single, oral
Highest studied dose
Dose: 200 mg
Route: oral
Route: single
Dose: 200 mg
Sources:
unhealthy, adult
Health Status: unhealthy
Age Group: adult
Sex: unknown
Sources:
Nausea and vomiting
200 mg single, oral
Highest studied dose
Dose: 200 mg
Route: oral
Route: single
Dose: 200 mg
Sources:
unhealthy, adult
Health Status: unhealthy
Age Group: adult
Sex: unknown
Sources:
Diarrhea 42%
430 mg 1 times / day steady, oral
Highest studied dose
Dose: 430 mg, 1 times / day
Route: oral
Route: steady
Dose: 430 mg, 1 times / day
Sources:
unhealthy, adult
Health Status: unhealthy
Age Group: adult
Sex: M
Sources:
Dry mouth 42%
430 mg 1 times / day steady, oral
Highest studied dose
Dose: 430 mg, 1 times / day
Route: oral
Route: steady
Dose: 430 mg, 1 times / day
Sources:
unhealthy, adult
Health Status: unhealthy
Age Group: adult
Sex: M
Sources:
Headaches 53%
430 mg 1 times / day steady, oral
Highest studied dose
Dose: 430 mg, 1 times / day
Route: oral
Route: steady
Dose: 430 mg, 1 times / day
Sources:
unhealthy, adult
Health Status: unhealthy
Age Group: adult
Sex: M
Sources:
Somnolence 25%
600 mg 1 times / day steady, oral
Highest studied dose
Dose: 600 mg, 1 times / day
Route: oral
Route: steady
Dose: 600 mg, 1 times / day
Sources:
unhealthy, adult
Health Status: unhealthy
Age Group: adult
Sex: unknown
Sources:
Light headedness 10%
600 mg 1 times / day steady, oral
Highest studied dose
Dose: 600 mg, 1 times / day
Route: oral
Route: steady
Dose: 600 mg, 1 times / day
Sources:
unhealthy, adult
Health Status: unhealthy
Age Group: adult
Sex: unknown
Sources:
Asthenia 11%
600 mg 1 times / day steady, oral
Highest studied dose
Dose: 600 mg, 1 times / day
Route: oral
Route: steady
Dose: 600 mg, 1 times / day
Sources:
unhealthy, adult
Health Status: unhealthy
Age Group: adult
Sex: unknown
Sources:
Constipation 14%
600 mg 1 times / day steady, oral
Highest studied dose
Dose: 600 mg, 1 times / day
Route: oral
Route: steady
Dose: 600 mg, 1 times / day
Sources:
unhealthy, adult
Health Status: unhealthy
Age Group: adult
Sex: unknown
Sources:
Dizziness 17%
600 mg 1 times / day steady, oral
Highest studied dose
Dose: 600 mg, 1 times / day
Route: oral
Route: steady
Dose: 600 mg, 1 times / day
Sources:
unhealthy, adult
Health Status: unhealthy
Age Group: adult
Sex: unknown
Sources:
Nausea 22%
600 mg 1 times / day steady, oral
Highest studied dose
Dose: 600 mg, 1 times / day
Route: oral
Route: steady
Dose: 600 mg, 1 times / day
Sources:
unhealthy, adult
Health Status: unhealthy
Age Group: adult
Sex: unknown
Sources:
Dry mouth 25%
600 mg 1 times / day steady, oral
Highest studied dose
Dose: 600 mg, 1 times / day
Route: oral
Route: steady
Dose: 600 mg, 1 times / day
Sources:
unhealthy, adult
Health Status: unhealthy
Age Group: adult
Sex: unknown
Sources:
Abnormal vision 7%
600 mg 1 times / day steady, oral
Highest studied dose
Dose: 600 mg, 1 times / day
Route: oral
Route: steady
Dose: 600 mg, 1 times / day
Sources:
unhealthy, adult
Health Status: unhealthy
Age Group: adult
Sex: unknown
Sources:
Confusion 7%
600 mg 1 times / day steady, oral
Highest studied dose
Dose: 600 mg, 1 times / day
Route: oral
Route: steady
Dose: 600 mg, 1 times / day
Sources:
unhealthy, adult
Health Status: unhealthy
Age Group: adult
Sex: unknown
Sources:
Blurred vision 9%
600 mg 1 times / day steady, oral
Highest studied dose
Dose: 600 mg, 1 times / day
Route: oral
Route: steady
Dose: 600 mg, 1 times / day
Sources:
unhealthy, adult
Health Status: unhealthy
Age Group: adult
Sex: unknown
Sources:
Agitation 1.2%
Disc. AE
600 mg 1 times / day steady, oral
Highest studied dose
Dose: 600 mg, 1 times / day
Route: oral
Route: steady
Dose: 600 mg, 1 times / day
Sources:
unhealthy, adult
Health Status: unhealthy
Age Group: adult
Sex: unknown
Sources:
Asthenia 1.3%
Disc. AE
600 mg 1 times / day steady, oral
Highest studied dose
Dose: 600 mg, 1 times / day
Route: oral
Route: steady
Dose: 600 mg, 1 times / day
Sources:
unhealthy, adult
Health Status: unhealthy
Age Group: adult
Sex: unknown
Sources:
Insomnia 1.5%
Disc. AE
600 mg 1 times / day steady, oral
Highest studied dose
Dose: 600 mg, 1 times / day
Route: oral
Route: steady
Dose: 600 mg, 1 times / day
Sources:
unhealthy, adult
Health Status: unhealthy
Age Group: adult
Sex: unknown
Sources:
Somnolence 1.5%
Disc. AE
600 mg 1 times / day steady, oral
Highest studied dose
Dose: 600 mg, 1 times / day
Route: oral
Route: steady
Dose: 600 mg, 1 times / day
Sources:
unhealthy, adult
Health Status: unhealthy
Age Group: adult
Sex: unknown
Sources:
Dizziness 1.9%
Disc. AE
600 mg 1 times / day steady, oral
Highest studied dose
Dose: 600 mg, 1 times / day
Route: oral
Route: steady
Dose: 600 mg, 1 times / day
Sources:
unhealthy, adult
Health Status: unhealthy
Age Group: adult
Sex: unknown
Sources:
Headache 2.9%
Disc. AE
600 mg 1 times / day steady, oral
Highest studied dose
Dose: 600 mg, 1 times / day
Route: oral
Route: steady
Dose: 600 mg, 1 times / day
Sources:
unhealthy, adult
Health Status: unhealthy
Age Group: adult
Sex: unknown
Sources:
Nausea 3.5%
Disc. AE
600 mg 1 times / day steady, oral
Highest studied dose
Dose: 600 mg, 1 times / day
Route: oral
Route: steady
Dose: 600 mg, 1 times / day
Sources:
unhealthy, adult
Health Status: unhealthy
Age Group: adult
Sex: unknown
Sources:
Nausea and vomiting
200 mg single, oral
Highest studied dose
Dose: 200 mg
Route: oral
Route: single
Dose: 200 mg
Sources:
healthy, elderly
Health Status: healthy
Age Group: elderly
Sex: unknown
Sources:
Nausea and vomiting
200 mg single, oral
Highest studied dose
Dose: 200 mg
Route: oral
Route: single
Dose: 200 mg
Sources:
healthy, younger
Health Status: healthy
Age Group: younger
Sex: unknown
Sources:
Overview

OverviewOther

Other InhibitorOther SubstrateOther Inducer




Drug as perpetrator​Drug as victimTox targets

Tox targets

TargetModalityActivityMetaboliteClinical evidence
PubMed

PubMed

TitleDatePubMed
Algorithm for the treatment of chronic depression.
2001
Bupropion and drug-induced parkinsonism.
2001 Aug
Opposite effects of nefazodone in two human models of anxiety.
2001 Aug
A probable interaction between a very low-dose oral contraceptive and the antidepressant nefazodone: a case report.
2001 Dec
Autonomic neurocardiac function in patients with major depression and effects of antidepressive treatment with nefazodone.
2001 Feb
P-glycoprotein interactions of nefazodone and trazodone in cell culture.
2001 Jul
A placebo-controlled, crossover trial of granisetron in SRI-induced sexual dysfunction.
2001 Jun
Which depressed patients respond to nefazodone and when?
2001 Mar
Prevalence of sexual dysfunction among newer antidepressants.
2002 Apr
Induction of hyperlocomotion in mice exposed to a novel environment by inhibition of serotonin reuptake. A pharmacological characterization of diverse classes of antidepressant agents.
2002 Apr
Human CYP3A4 and the metabolism of nefazodone and hydroxynefazodone by human liver microsomes and heterologously expressed enzymes.
2002 Apr
Sexual function and satisfaction in the treatment of chronic major depression with nefazodone, psychotherapy, and their combination.
2002 Aug
Nefazodone may increase anxiety in panic disorder.
2002 Feb
Evaluating changes in sexual functioning in depressed patients: sensitivity to change of the CSFQ.
2002 Mar-Apr
Antidepressant-induced sexual dysfunction.
2002 Oct
Patents

Sample Use Guides

Initial dose: 200 mg orally per day in two divided doses Maintenance dose: 300 to 600 mg orally per day
Route of Administration: Oral
In vitro biliary excretion of micafungin in humans and rats was reduced by 75% in the presence of the bile salt export pump (BSEP) inhibitor nefazodone (25 uM)
Name Type Language
NEFAZODONE HYDROCHLORIDE
MART.   MI   ORANGE BOOK   USAN   USP   USP-RS   WHO-DD  
USAN  
Official Name English
BMY 13754
Preferred Name English
NEFAZODONE HYDROCHLORIDE [MI]
Common Name English
NEFAZODONE HYDROCHLORIDE [ORANGE BOOK]
Common Name English
NEFAZODONE HYDROCHLORIDE [USP IMPURITY]
Common Name English
NEFAZODONE HYDROCHLORIDE [MART.]
Common Name English
NSC-760344
Code English
MJ 13,754-1
Code English
NEFAZODONE HYDROCHLORIDE [USP-RS]
Common Name English
NEFAZODONE HYDROCHLORIDE [USP MONOGRAPH]
Common Name English
2-(3-(4-(3-CHLOROPHENYL)-1-PIPERAZINYL)PROPYL)-5-ETHYL-2,4-DIHYDRO-4-(2-PHENOXYETHYL)-3H-1,2,4-TRIAZOL-3-ONE MONOHYDROCHLORIDE
Systematic Name English
BMY-13754
Code English
NEFAZODONE HYDROCHLORIDE [USAN]
Common Name English
Nefazodone hydrochloride [WHO-DD]
Common Name English
NEFAZODONE HCL
Common Name English
3H-1,2,4-TRIAZOL-3-ONE, 2-(3-(4-(3-CHLOROPHENYL)-1-PIPERAZINYL))PROPYL)-5-ETHYL-2,4-DIHYDRO-4-(2-PHENOXYETHYL)-, MONOHYDROCHLORIDE
Systematic Name English
MJ-13754-1
Code English
Classification Tree Code System Code
NCI_THESAURUS C265
Created by admin on Mon Mar 31 18:28:33 GMT 2025 , Edited by admin on Mon Mar 31 18:28:33 GMT 2025
Code System Code Type Description
RS_ITEM_NUM
1457902
Created by admin on Mon Mar 31 18:28:33 GMT 2025 , Edited by admin on Mon Mar 31 18:28:33 GMT 2025
PRIMARY
EVMPD
SUB03399MIG
Created by admin on Mon Mar 31 18:28:33 GMT 2025 , Edited by admin on Mon Mar 31 18:28:33 GMT 2025
PRIMARY
DRUG BANK
DBSALT000406
Created by admin on Mon Mar 31 18:28:33 GMT 2025 , Edited by admin on Mon Mar 31 18:28:33 GMT 2025
PRIMARY
NSC
760344
Created by admin on Mon Mar 31 18:28:33 GMT 2025 , Edited by admin on Mon Mar 31 18:28:33 GMT 2025
PRIMARY
CAS
82752-99-6
Created by admin on Mon Mar 31 18:28:33 GMT 2025 , Edited by admin on Mon Mar 31 18:28:33 GMT 2025
PRIMARY
EPA CompTox
DTXSID8046088
Created by admin on Mon Mar 31 18:28:33 GMT 2025 , Edited by admin on Mon Mar 31 18:28:33 GMT 2025
PRIMARY
ChEMBL
CHEMBL623
Created by admin on Mon Mar 31 18:28:33 GMT 2025 , Edited by admin on Mon Mar 31 18:28:33 GMT 2025
PRIMARY
RXCUI
236082
Created by admin on Mon Mar 31 18:28:33 GMT 2025 , Edited by admin on Mon Mar 31 18:28:33 GMT 2025
PRIMARY RxNorm
FDA UNII
27X63J94GR
Created by admin on Mon Mar 31 18:28:33 GMT 2025 , Edited by admin on Mon Mar 31 18:28:33 GMT 2025
PRIMARY
NCI_THESAURUS
C29283
Created by admin on Mon Mar 31 18:28:33 GMT 2025 , Edited by admin on Mon Mar 31 18:28:33 GMT 2025
PRIMARY
SMS_ID
100000085692
Created by admin on Mon Mar 31 18:28:33 GMT 2025 , Edited by admin on Mon Mar 31 18:28:33 GMT 2025
PRIMARY
DAILYMED
27X63J94GR
Created by admin on Mon Mar 31 18:28:33 GMT 2025 , Edited by admin on Mon Mar 31 18:28:33 GMT 2025
PRIMARY
CHEBI
7495
Created by admin on Mon Mar 31 18:28:33 GMT 2025 , Edited by admin on Mon Mar 31 18:28:33 GMT 2025
PRIMARY
MERCK INDEX
m7793
Created by admin on Mon Mar 31 18:28:33 GMT 2025 , Edited by admin on Mon Mar 31 18:28:33 GMT 2025
PRIMARY Merck Index
PUBCHEM
54911
Created by admin on Mon Mar 31 18:28:33 GMT 2025 , Edited by admin on Mon Mar 31 18:28:33 GMT 2025
PRIMARY