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
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
DescriptionSources: http://www.drugbank.ca/drugs/DB01149Curator's Comment: Description was created based on several sources, including
https://www.drugs.com/pro/nefazodone.html
Sources: http://www.drugbank.ca/drugs/DB01149
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
Sources: https://www.ncbi.nlm.nih.gov/pubmed/2274630
Curator's Comment: antidepressant
Originator
Sources: http://adisinsight.springer.com/drugs/800000656
Curator's Comment: # Bristol-Myers Squibb
Approval Year
Targets
Primary Target | Pharmacology | Condition | Potency |
---|---|---|---|
Target ID: CHEMBL224 Sources: http://www.drugbank.ca/drugs/DB01149 |
5.8 nM [Ki] | ||
Target ID: CHEMBL228 Sources: http://www.drugbank.ca/drugs/DB01149 |
290.0 nM [Ki] | ||
Target ID: CHEMBL2094251 Sources: https://www.ncbi.nlm.nih.gov/pubmed/9400006 |
5.5 nM [Ki] | ||
Target ID: CHEMBL2095158 Sources: https://www.ncbi.nlm.nih.gov/pubmed/9400006 |
84.0 nM [Ki] | ||
Target ID: CHEMBL214 Sources: http://www.drugbank.ca/drugs/DB01149 |
52.0 nM [Ki] |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
---|---|---|---|---|
Primary | NEFAZODONE HYDROCHLORIDE Approved UseNefazodone 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 Date2003 |
Cmax
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/8951188/ |
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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/8951188/ |
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
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/8951188/ |
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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/8951188/ |
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
Value | Dose | Co-administered | Analyte | Population |
---|---|---|---|---|
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 EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/8951188/ |
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
Dose | Population | Adverse events |
---|---|---|
200 mg single, oral Highest studied dose |
unhealthy, adult Health Status: unhealthy Age Group: adult Sex: unknown Sources: |
Other AEs: Nausea and vomiting... |
200 mg single, oral Highest studied dose |
unhealthy, adult Health Status: unhealthy Age Group: adult Sex: unknown Sources: |
Other AEs: Nausea and vomiting... |
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 |
Other AEs: Headaches, Dry mouth... Other AEs: Headaches (53%) Sources: Dry mouth (42%) Diarrhea (42%) |
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... |
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%) Sources: Nausea (22%) Dizziness (17%) Constipation (14%) Asthenia (11%) Light headedness (10%) Blurred vision (9%) Confusion (7%) 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: |
Disc. AE: Nausea, Headache... AEs leading to discontinuation/dose reduction: Nausea (3.5%) Sources: Headache (2.9%) Dizziness (1.9%) Somnolence (1.5%) Insomnia (1.5%) Asthenia (1.3%) Agitation (1.2%) |
200 mg single, oral Highest studied dose |
healthy, elderly Health Status: healthy Age Group: elderly Sex: unknown Sources: |
Other AEs: Nausea and vomiting... |
200 mg single, oral Highest studied dose |
healthy, younger Health Status: healthy Age Group: younger Sex: unknown Sources: |
Other AEs: Nausea and vomiting... |
AEs
AE | Significance | Dose | Population |
---|---|---|---|
Nausea and vomiting | 200 mg single, oral Highest studied dose |
unhealthy, adult Health Status: unhealthy Age Group: adult Sex: unknown Sources: |
|
Nausea and vomiting | 200 mg single, oral Highest studied dose |
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 |
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 |
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 |
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 |
healthy, elderly Health Status: healthy Age Group: elderly Sex: unknown Sources: |
|
Nausea and vomiting | 200 mg single, oral Highest studied dose |
healthy, younger Health Status: healthy Age Group: younger Sex: unknown Sources: |
Overview
CYP3A4 | CYP2C9 | CYP2D6 | hERG |
---|---|---|---|
OverviewOther
Other Inhibitor | Other Substrate | Other Inducer |
---|---|---|
Drug as perpetrator
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
no | ||||
weak | ||||
yes [IC50 4.7 uM] | ||||
yes [IC50 9 uM] | ||||
yes |
Drug as victim
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
no | ||||
yes | ||||
yes |
Tox targets
Target | Modality | Activity | Metabolite | Clinical evidence |
---|---|---|---|---|
PubMed
Title | Date | PubMed |
---|---|---|
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 |
Sample Use Guides
In Vivo Use Guide
Sources: https://www.drugs.com/dosage/nefazodone.html
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 Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/20606004
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)
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NCI_THESAURUS |
C265
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1457902
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SUB03399MIG
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DBSALT000406
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DTXSID8046088
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CHEMBL623
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236082
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27X63J94GR
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C29283
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m7793
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54911
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ACTIVE MOIETY
SUBSTANCE RECORD