PharmGKB: The Pharmacogenomics Knowledge Base

Drug/Small Molecule:
venlafaxine

2D structure

Overview

Generic Names: Venlafaxina [INN-Spanish]; Venlafaxine [INN:Ban]; Venlafaxinum [INN-Latin]
IUPAC Name: 1-[2-dimethylamino-1-(4-methoxyphenyl)ethyl]cyclohexan-1-ol
Trade Names: Effexor; Effexor XR; Elafax
PharmGKB Accession Id: PA451866

Description

Venlafaxine (Effexor) is an antidepressant of the serotonin-norepinephrine reuptake inhibitor (SNRI) class first introduced by Wyeth in 1993. It is prescribed for the treatment of clinical depression and anxiety disorders. Due to the pronounced side effects and suspicions that venlafaxine may significantly increase the risk of suicide it is not recommended as a first line treatment of depression. However, it is often effective for depression not responding to SSRIs. Venlafaxine was the sixth most widely-used antidepressant based on the amount of retail prescriptions in the US (17.1 million) in 2006. [Wikipedia]

Indication

For the treatment of severe depression

ATC Therapeutic Category

  • N06AX:Other antidepressants

Pharmacology and Interactions

Mechanism Of Action

Venlafaxine and its active metabolite, O-desmethylvenlafaxine (ODV), inhibit the reuptake of both serotonin and norepinephrine with a potency greater for the 5-HT than for the NE reuptake process. Both venlafaxine and the ODV metabolite have weak inhibitory effects on the reuptake of dopamine but, unlike the tricyclics and similar to SSRIs, they are not active at histaminergic, muscarinic, or alpha(1)-adrenergic receptors.

Pharmacology

Venlafaxine, an antidepressant agent structurally unrelated to other antidepressants, is used to treat melancholia, generalized anxiety disorder (GAD), panic disorder, post-traumatic stress disorder, and hot flashes in breast cancer survivors.

Food Interactions

Avoid St.John's Wort. Avoid alcohol. Take with food.

Absorption, Distribution, Metabolism, Elimination & Toxicity

Biotransformation

Hepatic

Protein Binding

27%

Absorption

Bioavailability is 45% following oral administration.

Half Life

5 hours

Toxicity

Most patients overdosing with venlafaxine develop only mild symptoms. However, severe toxicity is reported with the most common symptoms being CNS depression, serotonin toxicity, seizure, or cardiac conduction abnormalities. Venlafaxine's toxicity appears to be higher than other SSRIs, with a fatal toxic dose closer to that of the tricyclic antidepressants than the SSRIs. Doses of 900 mg or more are likely to cause moderate toxicity. Deaths have been reported following large doses.

Chemical Properties

Chemical Formula:

C17H27NO2

SMILES Code:

CN(C)CC(c1ccc(cc1)OC)C2(CCCCC2)O

(Format: OpenEye Isomeric)

Molecular Weight ( average / monoisotopic )

277.4018 / 277.2042

Curated Annotations (Curated Annotation)

  1. rs3800373 at chr6:35650454 in FKBP5
    This variant is associated with higher chance of response to anti-depressant drugs.
    Related Drugs:
    desipramine, fluoxetine, mirtazapine, venlafaxine
    Related Diseases:
    Depression
    Evidence:
    PMID:15565110
    PMID:18349090
    PMID:18597649
  2. rs1360780 at chr6:35715549 in FKBP5
    This variant is associated with higher chance of response to anti-depressant drugs.
    Related Drugs:
    desipramine, fluoxetine, mirtazapine, venlafaxine
    Related Diseases:
    Depression
    Evidence:
    PMID:15565111
    PMID:18349090
    PMID:18597649
  3. rs4148740 at chr7:86990039 in ABCB1
    This variant is associated with differences in clinical efficacy of antidepressants, most likely by influencing their access to the brain.
    Related Drugs:
    amitriptyline, citalopram, paroxetine, venlafaxine
    Related Diseases:
    Depression
    Evidence:
    PMID:18215618
  4. rs10280101 at chr7:86991521 in ABCB1
    This variant is associated with differences in clinical efficacy of antidepressants, most likely by influencing their access to the brain.
    Related Drugs:
    amitriptyline, citalopram, paroxetine, venlafaxine
    Related Diseases:
    Depression
    Evidence:
    PMID:18215618
  5. rs7787082 at chr7:86994987 in ABCB1
    This variant is associated with differences in clinical efficacy of antidepressants, most likely by influencing their access to the brain.
    Related Drugs:
    amitriptyline, citalopram, paroxetine, venlafaxine
    Related Diseases:
    Depression
    Evidence:
    PMID:18215618
  6. rs2032583 at chr7:86998497 in ABCB1
    This variant is associated with differences in clinical efficacy of antidepressants, most likely by influencing their access to the brain.
    Related Drugs:
    amitriptyline, citalopram, paroxetine, venlafaxine
    Related Diseases:
    Depression
    Evidence:
    PMID:18215618
  7. rs4148739 at chr7:86998985 in ABCB1
    This variant is associated with differences in clinical efficacy of antidepressants, most likely by influencing their access to the brain.
    Related Drugs:
    amitriptyline, citalopram, paroxetine, venlafaxine
    Related Diseases:
    Depression
    Evidence:
    PMID:18215618
  8. rs11983225 at chr7:86999456 in ABCB1
    This variant is associated with differences in clinical efficacy of antidepressants, most likely by influencing their access to the brain.
    Related Drugs:
    amitriptyline, citalopram, paroxetine, venlafaxine
    Related Diseases:
    Depression
    Evidence:
    PMID:18215618
  9. rs10248420 at chr7:87002922 in ABCB1
    This variant is associated with differences in clinical efficacy of antidepressants, most likely by influencing their access to the brain.
    Related Drugs:
    amitriptyline, citalopram, paroxetine, venlafaxine
    Related Diseases:
    Depression
    Evidence:
    PMID:18215618
  10. rs2235040 at chr7:87003686 in ABCB1
    This variant is associated with differences in clinical efficacy of antidepressants, most likely by influencing their access to the brain.
    Related Drugs:
    amitriptyline, citalopram, paroxetine, venlafaxine
    Related Diseases:
    Depression
    Evidence:
    PMID:18215618
  11. rs12720067 at chr7:87007292 in ABCB1
    This variant is associated with differences in clinical efficacy of antidepressants, most likely by influencing their access to the brain.
    Related Drugs:
    amitriptyline, citalopram, paroxetine, venlafaxine
    Related Diseases:
    Depression
    Evidence:
    PMID:18215618
  12. rs2235015 at chr7:87037500 in ABCB1
    This variant is associated with differences in clinical efficacy of antidepressants, most likely by influencing their access to the brain.
    Related Drugs:
    amitriptyline, citalopram, paroxetine, venlafaxine
    Related Diseases:
    Depression
    Evidence:
    PMID:18215618
  13. rs10897346 at chr11:55387401
    This SNP was significantly associated with response to therapy in 182 patient who received treatment for major depression.
    Related Drugs:
    mirtazapine, venlafaxine
    Related Diseases:
    Depression
    Evidence:
    PMID:18496129
  14. rs1487278 at chr12:70687118 in TPH2
    This SNP was significantly associated with response to therapy in 182 patient who received treatment for major depression.
    Related Drugs:
    mirtazapine, venlafaxine
    Related Diseases:
    Depression
    Evidence:
    PMID:18496129
  15. rs3892097 at chr22:40854891 in CYP2D6
    The variant allele CYP2D6*4 is the main polymorphism resulting in reduced enzyme activity in Caucasians. A number of studies show that poor metabolizer (PMs:*4/*4) reqiure a lower dose of drugs which get metabolized by CYP2D6.
    Variant Name:
    CYP2D6*4
    Related Drugs:
    clomipramine, codeine, desipramine, imipramine, nortriptyline, venlafaxine
    Related Diseases:
    Drug Toxicity
    Evidence:
    PMID:16958828
    PMID:1782973
    PMID:18070221
  16. rs3892097 at chr22:40854891 in CYP2D6
    This variant is diagnostic for the non-functional CYP2D6*4 haplotype. Individuals with CYP2D6 *6/*4 , *5/*4 or *6/*6 genotypes are poor metabolizers of venlafaxine and are more prone to drug-induced side effects such as nausea, vomiting and diarrhea. However, CYP2D6 genotype does not seem to influence venlafaxine efficacy.
    Variant Name:
    CYP2D6:1846G>A
    Related Drugs:
    venlafaxine
    Related Diseases:
    Depression, Depressive Disorder, Depressive Disorder, Major, Diarrhea, Drug Toxicity, Nausea, Vomiting
    Evidence:
    PMID:16958828
  17. rs5030655 at chr22:40855030 in CYP2D6
    This variant is the defining SNP for CYP2D6*6 and encodes a non-functional variant of CYP2D6. Individuals with CYP2D6 *6/*4 , *5/*4 or *6/*6 genotypes are poor metabolizers of venlafaxine and are more prone to drug-induced side effects such as nausea, vomiting and diarrhea. However, CYP2D6 genotype does not seem to influence venlafaxine efficacy.
    Variant Name:
    CYP2D6:1707 del T; CYP2D6*6
    Related Drugs:
    venlafaxine
    Related Diseases:
    Depression, Depressive Disorder, Depressive Disorder, Major, Diarrhea, Drug Toxicity, Nausea, Vomiting
    Evidence:
    PMID:16958828
Variant names are different names that have been used in the literature and other resources to refer to the same variant.

Curated Information

The following genes are in curated knowledge about this drug.

  Gene Relationship Evidence
Phenotype data available Genotype Data Available Literature annotations available Has annotations
ABCB1
  •   
  •   
  •   
  •   
  •   
Variants
Phenotype data available Genotype Data Available Literature annotations available Has annotations
CYP2C19
  •   
  •   
  • PK
  •   
  •   
Publications
Phenotype data available Genotype Data Available Literature annotations available Has annotations
CYP2C9
  •   
  •   
  • PK
  •   
  •   
Publications
Phenotype data available Genotype Data Available Literature annotations available Has annotations
CYP2D6
  • CO
  • PD
  • PK
  •   
  • GN
Publications, Variants
Phenotype data available Genotype Data Available Literature annotations available Not annotated
CYP3A
  •   
  •   
  • PK
  •   
  •   
Publications
Phenotype data available Genotype Data Available Literature annotations available Has annotations
CYP3A4
  • CO
  • PD
  • PK
  •   
  • GN
Publications
Phenotype data available Genotype Data Available Literature annotations available Has annotations
CYP3A5
  •   
  •   
  • PK
  •   
  •   
Publications
No phenotype data No genotype data Literature annotations available Has annotations
DRD2
  •   
  • PD
  •   
  •   
  • GN
Publications
No phenotype data No genotype data Literature annotations available Not annotated
FKBP5
  • CO
  •   
  •   
  •   
  • GN
Publications, Variants
No phenotype data Genotype Data Available Literature annotations available Not annotated
SLC6A3
  •   
  • PD
  •   
  •   
  • GN
Publications
No phenotype data No genotype data Literature annotations available Not annotated
SLC6A4
  • CO
  • PD
  • PK
  • FA
  • GN
Publications
No phenotype data No genotype data Literature annotations available Not annotated
TPH2
  •   
  •   
  •   
  •   
  •   
Variants

Non-Curated Information

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

Metabolizing Enzymes

Drug Targets

Curated Information

The following drugs are in curated knowledge about this drug.

  Drug Relationship Evidence
Phenotype data available Genotype Data Available Literature annotations available Not annotated
tamoxifen
  •   
  •   
  • PK
  •   
  •   
Publications
No phenotype data No genotype data Literature annotations available Not annotated
terbinafine
  •   
  •   
  • PK
  •   
  •   
Publications
No phenotype data No genotype data Literature annotations available Not annotated
voriconazole
  •   
  •   
  • PK
  •   
  •   
Publications

Non-Curated Information

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

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
  •   
  •   
  •   
  •   
Publications
Phenotype data available No genotype data Literature annotations available Not annotated
Depression
  • CO
  • PD
  • PK
  •   
  • GN
Publications, Variants
No phenotype data No genotype data Literature annotations available Not annotated
Depression, Postpartum
  • CO
  •   
  •   
  •   
  • GN
Publications
No phenotype data No genotype data Literature annotations available Not annotated
Depressive Disorder
  • CO
  • PD
  • PK
  •   
  • GN
Publications, Variants
No phenotype data No genotype data Literature annotations available Not annotated
Depressive Disorder, Major
  • CO
  • PD
  • PK
  •   
  • GN
Publications, Variants
No phenotype data No genotype data Literature annotations available Not annotated
Obsessive-Compulsive Disorder
  • CO
  •   
  •   
  •   
  •   
Publications
No phenotype data No genotype data Literature annotations available Not annotated
Posterior Cortical Atrophy
  • CO
  • PD
  •   
  •   
  •   
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:
DB00285
ChEBI ID:
9943
KEGG Compound ID:
C07187
PubChem Compound ID:
5656
PubChem Substance ID:
193901

Common Searches

Search PubMed
Search Medline Plus
Search PubChem
Search CTD

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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