PharmGKB: The Pharmacogenomics Knowledge Base

Drug/Small Molecule:
nefazodone

2D structure

Overview

Generic Names: Nefazodona [Spanish]; Nefazodone Hcl; Nefazodone Hydrochloride; Nefazodonum [Latin]
Trade Names: Dutonin; Serzone
PharmGKB Accession Id: PA450603

Description

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. Wikipedia (source: Drug Bank)

Indication

For the treatment of depression. (source: Drug Bank)

ATC Therapeutic Category

  • N06AX:Other antidepressants

Pharmacology, Interactions, and Contraindications

Mechanism Of Action

Within the serotonergic system, nefazodone acts as an antagonist at type 2 serotonin (5-HT<sub>2</sub>) 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. (source: Drug Bank)

Pharmacology

Nefazodone, an antidepressant synthetically derived phenylpiperazine, is used to treat major depression. Although it is structurally similar to trazodone, nefazodone has a mechanism of action different from other antidepressants and, hence, lacks the risk for major cardiovascular toxicity seen with tricyclics and insomnia and inhibition of REM sleep seen with the selective serotonin reuptake inhibitors. (source: Drug Bank)

Food Interactions

Avoid alcohol.
Avoid avocado.
Limit garlic, ginger, gingko, and horse chestnut.
Take this medication either consistently with or without food as instructed by your doctor. (source: Drug Bank)

Absorption, Distribution, Metabolism, Elimination & Toxicity

Biotransformation

Hepatic. (source: Drug Bank)

Protein Binding

Greater than 99% (in vitro, human plasma proteins). (source: Drug Bank)

Absorption

Nefazodone is rapidly and completely absorbed. Its absolute bioavailability is low (about 20%). (source: Drug Bank)

Toxicity

Cases of life-threatening hepatic failure have been reported in patients treated
with nefazodone. (source: Drug Bank)

Isomeric SMILES Code:

CCc1nn(c(=O)n1CCOc2ccccc2)CCCN3CCN(CC3)c4cccc(c4)Cl (source: Drug Bank)

The following genes are in curated knowledge about this drug.

  Gene Relationship Evidence
Phenotype data available Genotype Data Available Literature annotations available Has annotations
CYP3A4
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  • PK
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Publications

A list of non-curated publications that mention this drug along with other genes is available.

Drug Targets

Gene Description
HTR2A Uncurated Annotation (source: Drug Bank)
ADRA1A Uncurated Annotation (source: Drug Bank)
ADRA1B Uncurated Annotation (source: Drug Bank)
SLC6A2 Uncurated Annotation (source: Drug Bank)
SLC6A4 Uncurated Annotation (source: Drug Bank)

The following drugs are in curated knowledge about this drug.

  Drug Relationship Evidence
No phenotype data No genotype data Literature annotations available Not annotated
bupropion
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  •   
  • FA
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Publications

A list of non-curated publications that mention this drug along with other drugs is available.

Drug Interactions

Drug Description
almotriptan Uncurated Annotation Increased risk of CNS adverse effects (source: Drug Bank)
astemizole Uncurated Annotation Increased risk of cardiotoxicity and arrhythmias (source: Drug Bank)
atorvastatin Uncurated Annotation Nefazodone increases the effect and toxicity of the statin drug (source: Drug Bank)
buspirone Uncurated Annotation Nefazodone increases the effect of buspirone (source: Drug Bank)
carbamazepine Uncurated Annotation Nefazodone increases the effect of carbamazepine (source: Drug Bank)
cerivastatin Uncurated Annotation Nefazodone increases the effect and toxicity of the statin drug (source: Drug Bank)
cisapride Uncurated Annotation Nefazodone increases serum levels of cisapride (source: Drug Bank)
cyclosporine Uncurated Annotation The antidepressant increases the effect and toxicity of cyclosporine (source: Drug Bank)
eletriptan Uncurated Annotation Increased risk of CNS adverse effects (source: Drug Bank)
erlotinib Uncurated Annotation This CYP3A4 inhibitor increases levels/toxicity of erlotinib (source: Drug Bank)
isocarboxazid Uncurated Annotation Possible severe adverse reaction with this combination (source: Drug Bank)
linezolid Uncurated Annotation Combination associated with possible serotoninergic syndrome (source: Drug Bank)
loratadine Uncurated Annotation Increased risk of cardiotoxicity (source: Drug Bank)
lovastatin Uncurated Annotation Nefazodone increases the effect and toxicity of the statin drug (source: Drug Bank)
naratriptan Uncurated Annotation Increased risk of CNS adverse effects (source: Drug Bank)
phenelzine Uncurated Annotation Possible severe adverse reaction with this combination (source: Drug Bank)
pimozide Uncurated Annotation Nefazodone increases the effect and toxicity of pimozide (source: Drug Bank)
rizatriptan Uncurated Annotation Increased risk of CNS adverse effects (source: Drug Bank)
sibutramine Uncurated Annotation Risk of serotoninergic syndrome (source: Drug Bank)
simvastatin Uncurated Annotation Nefazodone increases the effect and toxicity of the statin drug (source: Drug Bank)
sumatriptan Uncurated Annotation Increased risk of CNS adverse effects (source: Drug Bank)
sunitinib Uncurated Annotation Possible increase in sunitinib levels (source: Drug Bank)
tacrolimus Uncurated Annotation Nefazodone increases the effect and toxicity of tacrolimus (source: Drug Bank)
terfenadine Uncurated Annotation Increased risk of cardiotoxicity and arrhythmias (source: Drug Bank)
tramadol Uncurated Annotation Increased risk of serotonin syndrome (source: Drug Bank)
tranylcypromine Uncurated Annotation Possible severe adverse reaction with this combination (source: Drug Bank)
trazodone Uncurated Annotation This strong CYP3A4 inhibitor increases the effect and toxicity of trazodone (source: Drug Bank)
triazolam Uncurated Annotation Nefazodone increases the effect of triazolam (source: Drug Bank)
zolmitriptan Uncurated Annotation Increased risk of CNS adverse effects (source: Drug Bank)

Curated Information

The following diseases are in curated knowledge about this drug.

  Disease Relationship Evidence
No phenotype data No genotype data Literature annotations available Not annotated
Anxiety Disorders
  • CO
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Publications
No phenotype data No genotype data Literature annotations available Not annotated
Depressive Disorder, Major
  • CO
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Publications
No phenotype data No genotype data Literature annotations available Not annotated
Obsessive-Compulsive Disorder
  • CO
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  •   
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Publications
No phenotype data No genotype data Literature annotations available Not annotated
Toxic liver disease
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  • PD
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Publications

Non-Curated Information

A list of non-curated publications that mention this drug along with other diseases is available.

Additional Datasets

These datasets are minimally curated and are sorted alphabetically by title.

  1. Physicochemical determinants of human renal clearance

LinkOuts

Web Resource:
Wikipedia
DrugBank:
DB01149
KEGG Compound ID:
C07256
PubChem Compound ID:
4449
PubChem Substance ID:
205126

Common Searches

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Non-Curated Publications

A list of non-curated publications that mention this drug is available.

PharmGKB integrates drug information from different sources: DrugBank, Open Eye Scientific Software.
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