Venlafaxine

Identification

Summary

Venlafaxine is a selective serotonin and norepinephrine reuptake inhibitor (SNRI) used for the treatment of major depression, generalized or social anxiety disorder, and panic disorder.

Brand Names
Effexor
Generic Name
Venlafaxine
DrugBank Accession Number
DB00285
Background

Venlafaxine is an antidepressant and a serotonin and norepinephrine reuptake inhibitor (SNRI). Its active metabolite, desvenlafaxine, works by blocking the reuptake of serotonin and norepinephrine, which are key neurotransmitters in mood regulation. Venlafaxine is officially approved to treat major depressive disorder (MDD), generalized anxiety disorder (GAD), social anxiety disorder, and panic disorder in adults.17 The immediate formulation of the drug, marketed as Effexor, was first approved by the FDA in 1993 and the extended-release formulation, Effexor XR, was later introduced in 1997.11

Venlafaxine has been used as a first-line treatment for MDD, GAD, social anxiety disorder, and panic disorder in Canada for many years. It was also considered a second-line treatment for obsessive-compulsive disorder (OCD).2,5 Venlafaxine was also investigated in off-label uses for the prophylaxis of migraine headaches,1,3 for reduction of vasomotor symptoms associated with menopause,6 and for the management of neuropathic pain (although there is only minimal evidence of efficacy for this condition).4

Type
Small Molecule
Groups
Approved
Structure
Weight
Average: 277.4018
Monoisotopic: 277.204179113
Chemical Formula
C17H27NO2
Synonyms
  • Venlafaxina
  • Venlafaxine
  • Venlafaxinum

Pharmacology

Indication

Venlafaxine is indicated for the management of major depressive disorder (MDD), generalized anxiety disorder (GAD), social anxiety disorder (SAD), and panic disorder.17

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Associated Conditions
Indication TypeIndicationCombined Product DetailsApproval LevelAge GroupPatient CharacteristicsDose Form
Management ofGeneralized anxiety disorder••••••••••••••••••••••••• •••••••• •••••••• ••••••• •••••••• •••••••
Management ofMajor depressive disorder (mdd)••••••••••••••••••••••••• •••••••• •••••••• ••••••• •••••••• •••••••
Prophylaxis ofMigraine••• •••••
Management ofNeuropathic pain••• •••••
Management ofPanic disorder••••••••••••••••••••••••• •••••••• •••••••
Contraindications & Blackbox Warnings
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Pharmacodynamics

Venlafaxine is an antidepressant agent that works to ameliorate the symptoms of various psychiatric disorders by increasing the level of neurotransmitters in the synapse. Venlafaxine does not mediate muscarinic, histaminergic, or adrenergic effects.17

Mechanism of action

The exact mechanism of action of venlafaxine in the treatment of various psychiatric conditions has not been fully elucidated; however, it is understood that venlafaxine and its active metabolite O-desmethylvenlafaxine (ODV) potently and selectively inhibits the reuptake of both serotonin and norepinephrine at the presynaptic terminal.7,11,17 This results in increased levels of neurotransmitters available at the synapse that can stimulate postsynaptic receptors.13 It is suggested that venlafaxine has a 30-fold selectivity for serotonin compared to norepinephrine: venlafaxine initially inhibits serotonin reuptake at low doses, and with higher doses, it inhibits norepinephrine reuptake in addition to serotonin.11,12 Venlafaxine and ODV are also weak inhibitors of dopamine reuptake.17

TargetActionsOrganism
ASodium-dependent serotonin transporter
inhibitor
Humans
ASodium-dependent noradrenaline transporter
inhibitor
Humans
USodium-dependent dopamine transporter
inhibitor
Humans
Absorption

Venlafaxine is well absorbed after oral administration with an absolute bioavailability of approximately 45%. In mass balance studies, at least 92% of a single oral dose of venlafaxine was absorbed. After twice-daily oral administration of immediate-release formulation of 150 mg venlafaxine, Cmax was 150 ng/mL and Tmax was 5.5 hours. Cmax and Tmax of ODV were 260 ng/mL and nine hours, respectively. The extended-release formulation of venlafaxine has a slower rate of absorption, but the same extent of absorption as the immediate-release formulation. After once-daily administration of extended-release formulation of 75 mg venlafaxine, Cmax was 225 ng/mL and Tmax was two hours. Cmax and Tmax of ODV were 290 ng/mL and three hours, respectively.17

Food does not affect the bioavailability of venlafaxine or its active metabolite, O-desmethylvenlafaxine (ODV).17

Volume of distribution

The apparent volume of distribution at steady-state is 7.5 ± 3.7 L/kg for venlafaxine and 5.7 ± 1.8 L/kg for ODV.17

Protein binding

Venlafaxine and ODV is 27% and 30% bound to plasma proteins, respectively.17

Metabolism

Following absorption, venlafaxine undergoes extensive presystemic metabolism in the liver. It primarily undergoes CYP2D6-mediated demethylation to form its active metabolite O-desmethylvenlafaxine (ODV).17 Venlafaxine can also undergo N-demethylation mediated by CYP2C9, and CYP2C19, and CYP3A4 to form N-desmethylvenlafaxine (NDV) but this is a minor metabolic pathway.8 ODV and NDV further metabolized by CYP2C19, CYP2D6 and/or CYP3A4 to form N,O-didesmethylvenlafaxine (NODV) 9 and NODV can be further metabolized to form N, N, O-tridesmethylvenlafaxine, followed by a possible glucuronidation.10

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Route of elimination

Approximately 87% of a venlafaxine dose is recovered in the urine within 48 hours as unchanged venlafaxine (5%), unconjugated ODV (29%), conjugated ODV (26%), or other minor inactive metabolites (27%).17

Half-life

The apparent elimination half-life is 5 ± 2 hours for venlafaxine and 11 ± 2 hours for ODV.17

Clearance

Mean ± SD plasma apparent clearance at steady-state is 1.3 ± 0.6 L/h/kg for venlafaxine and 0.4 ± 0.2 L/h/kg for ODV.17

Adverse Effects
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Toxicity

Oral LD50 was 350 mg/kg in female rats and 700 mg/kg in male rats.16

There are reports of acute overdosage with venlafaxine either alone or in combination with other drugs including alcohol. Doses up to several-fold higher than the usual therapeutic dose have been ingested in these cases of acute overdosage. Somnolence is the most commonly reported symptom, along with other symptoms such as paresthesia of the extremities, moderate dizziness, altered consciousness, nausea, vomiting, numb hands and feet, hot-cold spells (which occur a few days after the overdose event), hypotension, convulsions, sinus and ventricular tachycardia, rhabdomyolysis, vertigo, liver necrosis, electrocardiogram changes (e.g., prolongation of QT interval, bundle branch block, QRS prolongation), serotonin syndrome, and death.17

There is no known antidote for venlafaxine overdose. Cases of overdose have been managed with or without symptomatic treatment, hospitalization, and activated charcoal.17

Retrospective studies suggest that the risk of fatal outcomes from venlafaxine overdosage is higher than that of SSRI antidepressants, but lower than that of tricyclic antidepressants.17

Pathways
PathwayCategory
Venlafaxine Metabolism PathwayDrug metabolism
Pharmacogenomic Effects/ADRs
Interacting Gene/EnzymeAllele nameGenotype(s)Defining Change(s)Type(s)DescriptionDetails
Cytochrome P450 2D6CYP2D6*4(A;A)A AlleleEffect Directly StudiedPatients with this genotype have reduced metabolism of venlafaxine.Details
Cytochrome P450 2D6CYP2D6*6(-;T) / (-;-)T deletion / T deletion, homozygoteEffect Directly StudiedPatients with this genotype have reduced metabolism of venlafaxine.Details
Cytochrome P450 2D6CYP2D6*5Not AvailableWhole gene deletion, homozygoteEffect Directly StudiedPatients with this genotype have reduced metabolism of venlafaxine.Details
Multidrug resistance protein 1---(C;C) / (C;T)C AlleleEffect Directly StudiedPatients with this genotype have an increased likelihood of remission when using venlafaxine to treat major depressive disorderDetails
Multidrug resistance protein 1---(C;C) / (C;T)T > CEffect Directly StudiedPatients with this genotype have increased risk of adverse events with venlafaxineDetails
Cytochrome P450 2D6CYP2D6*3Not AvailableC alleleEffect InferredPoor drug metabolizer, lower dose requirements, nausea, vomiting and diarrheaDetails
Cytochrome P450 2D6CYP2D6*7Not Available2935A>CEffect InferredPoor drug metabolizer, lower dose requirements, nausea, vomiting and diarrheaDetails
Cytochrome P450 2D6CYP2D6*8Not Available1758G>TEffect InferredPoor drug metabolizer, lower dose requirements, nausea, vomiting and diarrheaDetails
Cytochrome P450 2D6CYP2D6*11Not Available883G>CEffect InferredPoor drug metabolizer, lower dose requirements, nausea, vomiting and diarrheaDetails
Cytochrome P450 2D6CYP2D6*12Not Available124G>AEffect InferredPoor drug metabolizer, lower dose requirements, nausea, vomiting and diarrheaDetails
Cytochrome P450 2D6CYP2D6*13Not AvailableCYP2D7/2D6 hybrid gene structureEffect InferredPoor drug metabolizer, lower dose requirements, nausea, vomiting and diarrheaDetails
Cytochrome P450 2D6CYP2D6*14ANot Available1758G>AEffect InferredPoor drug metabolizer, lower dose requirements, nausea, vomiting and diarrheaDetails
Cytochrome P450 2D6CYP2D6*15Not Available137insT, 137_138insTEffect InferredPoor drug metabolizer, lower dose requirements, nausea, vomiting and diarrheaDetails
Cytochrome P450 2D6CYP2D6*19Not Available2539_2542delAACTEffect InferredPoor drug metabolizer, lower dose requirements, nausea, vomiting and diarrheaDetails
Cytochrome P450 2D6CYP2D6*20Not Available1973_1974insGEffect InferredPoor drug metabolizer, lower dose requirements, nausea, vomiting and diarrheaDetails
Cytochrome P450 2D6CYP2D6*21Not Available2573insCEffect InferredPoor drug metabolizer, lower dose requirements, nausea, vomiting and diarrheaDetails
Cytochrome P450 2D6CYP2D6*31Not Available-1770G>A / -1584C>G  … show all Effect InferredPoor drug metabolizer, lower dose requirements, nausea, vomiting and diarrheaDetails
Cytochrome P450 2D6CYP2D6*36Not Available100C>T / -1426C>T  … show all Effect InferredPoor drug metabolizer, lower dose requirements, nausea, vomiting and diarrheaDetails
Cytochrome P450 2D6CYP2D6*38Not Available2587_2590delGACTEffect InferredPoor drug metabolizer, lower dose requirements, nausea, vomiting and diarrheaDetails
Cytochrome P450 2D6CYP2D6*40Not Available1863_1864ins(TTT CGC CCC)2Effect InferredPoor drug metabolizer, lower dose requirements, nausea, vomiting and diarrheaDetails
Cytochrome P450 2D6CYP2D6*42Not Available3259_3260insGTEffect InferredPoor drug metabolizer, lower dose requirements, nausea, vomiting and diarrheaDetails
Cytochrome P450 2D6CYP2D6*44Not Available2950G>CEffect InferredPoor drug metabolizer, lower dose requirements, nausea, vomiting and diarrheaDetails
Cytochrome P450 2D6CYP2D6*47Not Available100C>T / -1426C>T  … show all Effect InferredPoor drug metabolizer, lower dose requirements, nausea, vomiting and diarrheaDetails
Cytochrome P450 2D6CYP2D6*51Not Available-1584C>G / -1235A>G  … show all Effect InferredPoor drug metabolizer, lower dose requirements, nausea, vomiting and diarrheaDetails
Cytochrome P450 2D6CYP2D6*56Not Available3201C>TEffect InferredPoor drug metabolizer, lower dose requirements, nausea, vomiting and diarrheaDetails
Cytochrome P450 2D6CYP2D6*57Not Available100C>T / 310G>T  … show all Effect InferredPoor drug metabolizer, lower dose requirements, nausea, vomiting and diarrheaDetails
Cytochrome P450 2D6CYP2D6*62Not Available4044C>TEffect InferredPoor drug metabolizer, lower dose requirements, nausea, vomiting and diarrheaDetails
Cytochrome P450 2D6CYP2D6*68ANot Available-1426C>T / -1235A>G  … show all Effect InferredPoor drug metabolizer, lower dose requirements, nausea, vomiting and diarrheaDetails
Cytochrome P450 2D6CYP2D6*68BNot AvailableSimilar but not identical switch region compared to CYP2D6*68A. Found in tandem arrangement with CYP2D6*4.Effect InferredPoor drug metabolizer, lower dose requirements, nausea, vomiting and diarrheaDetails
Cytochrome P450 2D6CYP2D6*69Not Available2988G>A / -1426C>T  … show all Effect InferredPoor drug metabolizer, lower dose requirements, nausea, vomiting and diarrheaDetails
Cytochrome P450 2D6CYP2D6*92Not Available1995delCEffect InferredPoor drug metabolizer, lower dose requirements, nausea, vomiting and diarrheaDetails
Cytochrome P450 2D6CYP2D6*100Not Available-1426C>T / -1235A>G  … show all Effect InferredPoor drug metabolizer, lower dose requirements, nausea, vomiting and diarrheaDetails
Cytochrome P450 2D6CYP2D6*101Not Available-1426C>T / -1235A>G  … show all Effect InferredPoor drug metabolizer, lower dose requirements, nausea, vomiting and diarrheaDetails

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
1,2-BenzodiazepineThe risk or severity of CNS depression can be increased when Venlafaxine is combined with 1,2-Benzodiazepine.
AbacavirVenlafaxine may decrease the excretion rate of Abacavir which could result in a higher serum level.
AbametapirThe serum concentration of Venlafaxine can be increased when it is combined with Abametapir.
AbataceptThe metabolism of Venlafaxine can be increased when combined with Abatacept.
AbciximabThe risk or severity of bleeding can be increased when Abciximab is combined with Venlafaxine.
Food Interactions
  • Avoid alcohol. The safety of using venlafaxine with other CNS-active drugs, including alcohol, has not been evaluated.
  • Avoid St. John's Wort. Co-administration of St. John's Wort may lead to additive serotonergic activity and an increased risk of serotonin syndrome.
  • Take with food. Co-administration with food helps to alleviate or mitigate gastrointestinal upset.

Products

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Product Ingredients
IngredientUNIICASInChI Key
Venlafaxine besylate monohydrate18XP3YT5NH609345-59-7XHPQSXIKZWZGIP-UHFFFAOYSA-N
Venlafaxine hydrochloride7D7RX5A8MO99300-78-4QYRYFNHXARDNFZ-UHFFFAOYSA-N
Product Images
International/Other Brands
Elafax
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
Act Venlafaxine XRCapsule, extended release150 mgOralTEVA Canada Limited2008-02-13Not applicableCanada flag
Act Venlafaxine XRCapsule, extended release75 mgOralTEVA Canada Limited2008-02-13Not applicableCanada flag
Act Venlafaxine XRCapsule, extended release37.5 mgOralTEVA Canada Limited2008-02-13Not applicableCanada flag
EffexorTablet37.5 mg/1OralPhysicians Total Care, Inc.1993-12-012011-05-31US flag
EffexorTablet25 mg/1OralWyeth Pharmaceuticals Company, a subsidiary of Pfizer Inc.1993-12-012011-05-01US flag
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
Apo-venlafaxine XRCapsule, extended release37.5 mgOralApotex Corporation2013-04-16Not applicableCanada flag
Apo-venlafaxine XRCapsule, extended release75 mgOralApotex Corporation2013-04-16Not applicableCanada flag
Apo-venlafaxine XRCapsule, extended release150 mgOralApotex Corporation2013-04-16Not applicableCanada flag
Auro-venlafaxine XRCapsule, extended release75 mgOralAuro Pharma Inc2016-03-14Not applicableCanada flag
Auro-venlafaxine XRCapsule, extended release150 mgOralAuro Pharma Inc2016-03-14Not applicableCanada flag

Categories

ATC Codes
N06AX16 — Venlafaxine
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as anisoles. These are organic compounds containing a methoxybenzene or a derivative thereof.
Kingdom
Organic compounds
Super Class
Benzenoids
Class
Phenol ethers
Sub Class
Anisoles
Direct Parent
Anisoles
Alternative Parents
Phenoxy compounds / Methoxybenzenes / Cyclohexanols / Aralkylamines / Alkyl aryl ethers / Tertiary alcohols / 1,3-aminoalcohols / Trialkylamines / Cyclic alcohols and derivatives / Organopnictogen compounds
show 1 more
Substituents
1,3-aminoalcohol / Alcohol / Alkyl aryl ether / Amine / Anisole / Aralkylamine / Aromatic homomonocyclic compound / Cyclic alcohol / Cyclohexanol / Ether
show 12 more
Molecular Framework
Aromatic homomonocyclic compounds
External Descriptors
tertiary alcohol, tertiary amino compound, monomethoxybenzene, cyclohexanols (CHEBI:9943)
Affected organisms
  • Humans and other mammals

Chemical Identifiers

UNII
GRZ5RCB1QG
CAS number
93413-69-5
InChI Key
PNVNVHUZROJLTJ-UHFFFAOYSA-N
InChI
InChI=1S/C17H27NO2/c1-18(2)13-16(17(19)11-5-4-6-12-17)14-7-9-15(20-3)10-8-14/h7-10,16,19H,4-6,11-13H2,1-3H3
IUPAC Name
1-[2-(dimethylamino)-1-(4-methoxyphenyl)ethyl]cyclohexan-1-ol
SMILES
COC1=CC=C(C=C1)C(CN(C)C)C1(O)CCCCC1

References

Synthesis Reference

Thomas P. Jerussi, Chrisantha H. Senanayake, "Derivatives of (+)-venlafaxine and methods of preparing and using the same." U.S. Patent US6197828, issued June, 1994.

US6197828
General References
  1. Ozyalcin SN, Talu GK, Kiziltan E, Yucel B, Ertas M, Disci R: The efficacy and safety of venlafaxine in the prophylaxis of migraine. Headache. 2005 Feb;45(2):144-52. [Article]
  2. Kennedy SH, Lam RW, McIntyre RS, Tourjman SV, Bhat V, Blier P, Hasnain M, Jollant F, Levitt AJ, MacQueen GM, McInerney SJ, McIntosh D, Milev RV, Muller DJ, Parikh SV, Pearson NL, Ravindran AV, Uher R: Canadian Network for Mood and Anxiety Treatments (CANMAT) 2016 Clinical Guidelines for the Management of Adults with Major Depressive Disorder: Section 3. Pharmacological Treatments. Can J Psychiatry. 2016 Sep;61(9):540-60. doi: 10.1177/0706743716659417. Epub 2016 Aug 2. [Article]
  3. Pringsheim T, Davenport W, Mackie G, Worthington I, Aube M, Christie SN, Gladstone J, Becker WJ: Canadian Headache Society guideline for migraine prophylaxis. Can J Neurol Sci. 2012 Mar;39(2 Suppl 2):S1-59. [Article]
  4. Gallagher HC, Gallagher RM, Butler M, Buggy DJ, Henman MC: Venlafaxine for neuropathic pain in adults. Cochrane Database Syst Rev. 2015 Aug 23;(8):CD011091. doi: 10.1002/14651858.CD011091.pub2. [Article]
  5. Katzman MA, Bleau P, Blier P, Chokka P, Kjernisted K, Van Ameringen M, Antony MM, Bouchard S, Brunet A, Flament M, Grigoriadis S, Mendlowitz S, O'Connor K, Rabheru K, Richter PM, Robichaud M, Walker JR: Canadian clinical practice guidelines for the management of anxiety, posttraumatic stress and obsessive-compulsive disorders. BMC Psychiatry. 2014;14 Suppl 1:S1. doi: 10.1186/1471-244X-14-S1-S1. Epub 2014 Jul 2. [Article]
  6. Handley AP, Williams M: The efficacy and tolerability of SSRI/SNRIs in the treatment of vasomotor symptoms in menopausal women: a systematic review. J Am Assoc Nurse Pract. 2015 Jan;27(1):54-61. doi: 10.1002/2327-6924.12137. Epub 2014 Jun 19. [Article]
  7. Bymaster FP, Dreshfield-Ahmad LJ, Threlkeld PG, Shaw JL, Thompson L, Nelson DL, Hemrick-Luecke SK, Wong DT: Comparative affinity of duloxetine and venlafaxine for serotonin and norepinephrine transporters in vitro and in vivo, human serotonin receptor subtypes, and other neuronal receptors. Neuropsychopharmacology. 2001 Dec;25(6):871-80. [Article]
  8. Fogelman SM, Schmider J, Venkatakrishnan K, von Moltke LL, Harmatz JS, Shader RI, Greenblatt DJ: O- and N-demethylation of venlafaxine in vitro by human liver microsomes and by microsomes from cDNA-transfected cells: effect of metabolic inhibitors and SSRI antidepressants. Neuropsychopharmacology. 1999 May;20(5):480-90. [Article]
  9. Preskorn S, Patroneva A, Silman H, Jiang Q, Isler JA, Burczynski ME, Ahmed S, Paul J, Nichols AI: Comparison of the pharmacokinetics of venlafaxine extended release and desvenlafaxine in extensive and poor cytochrome P450 2D6 metabolizers. J Clin Psychopharmacol. 2009 Feb;29(1):39-43. doi: 10.1097/JCP.0b013e318192e4c1. [Article]
  10. Howell SR, Husbands GE, Scatina JA, Sisenwine SF: Metabolic disposition of 14C-venlafaxine in mouse, rat, dog, rhesus monkey and man. Xenobiotica. 1993 Apr;23(4):349-59. [Article]
  11. Sansone RA, Sansone LA: Serotonin norepinephrine reuptake inhibitors: a pharmacological comparison. Innov Clin Neurosci. 2014 Mar;11(3-4):37-42. [Article]
  12. Stahl SM, Grady MM, Moret C, Briley M: SNRIs: their pharmacology, clinical efficacy, and tolerability in comparison with other classes of antidepressants. CNS Spectr. 2005 Sep;10(9):732-47. doi: 10.1017/s1092852900019726. [Article]
  13. Singh D, Saadabadi A: Venlafaxine . [Article]
  14. FDA Approved Drug Products: Effexor XR® extended-release capsules [Link]
  15. FDA Approved Drug Products: EFFEXOR XR (venlafaxine) Extended-Release Capsules (November 2021) [Link]
  16. Pfizer: EFFEXOR (Venlafaxine Hydrochloride Modified Release) MSDS [Link]
  17. FDA Approved Drug Products: EFFEXOR XR (venlafaxine extended-release) capsules, for oral use (August 2022) [Link]
  18. FDA Approved Drug Products: EFFEXOR XR (venlafaxine extended-release) capsules, for oral use (August 2023) [Link]
Human Metabolome Database
HMDB0005016
KEGG Drug
D08670
KEGG Compound
C07187
PubChem Compound
5656
PubChem Substance
46504593
ChemSpider
5454
BindingDB
82071
RxNav
39786
ChEBI
9943
ChEMBL
CHEMBL637
Therapeutic Targets Database
DAP000054
PharmGKB
PA451866
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
PDRhealth
PDRhealth Drug Page
Wikipedia
Venlafaxine

Clinical Trials

Clinical Trials
Clinical Trial & Rare Diseases Add-on Data Package
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PhaseStatusPurposeConditionsCountStart DateWhy Stopped100+ additional columns
Not AvailableCompletedNot AvailableAcute Kidney Injury (AKI) / Depression1somestatusstop reasonjust information to hide
Not AvailableCompletedNot AvailableAntidepressants / Pharmacokinetics / Pregnancy1somestatusstop reasonjust information to hide
Not AvailableCompletedNot AvailableBreast Cancer / Depression / Hot Flashes / Psychosocial Effects of Cancer and Its Treatment1somestatusstop reasonjust information to hide
Not AvailableCompletedNot AvailableDepression1somestatusstop reasonjust information to hide
Not AvailableCompletedNot AvailableDepression / Depressive Disorder / Inflammation1somestatusstop reasonjust information to hide

Pharmacoeconomics

Manufacturers
  • Wyeth pharmaceuticals inc
  • Teva pharmaceuticals usa inc
  • Osmotica pharmaceutical corp
  • Actavis totowa llc
  • Amneal pharmaceuticals
  • Aurobindo pharma ltd
  • Caraco pharmaceutical laboratories ltd
  • Dr reddys laboratories ltd
  • Mylan pharmaceuticals inc
  • Pliva hrvatska doo
  • Sandoz inc
  • Vintage pharmaceuticals llc
  • Zydus pharmaceuticals usa inc
  • Wyeth
Packagers
  • Advanced Pharmaceutical Services Inc.
  • Amerisource Health Services Corp.
  • AQ Pharmaceuticals Inc.
  • A-S Medication Solutions LLC
  • Bryant Ranch Prepack
  • Cadila Healthcare Ltd.
  • Caraco Pharmaceutical Labs
  • Cardinal Health
  • Caremark LLC
  • Direct Pharmaceuticals Inc.
  • Dispensing Solutions
  • Diversified Healthcare Services Inc.
  • Doctor Reddys Laboratories Ltd.
  • Heartland Repack Services LLC
  • Innoviant Pharmacy Inc.
  • Kaiser Foundation Hospital
  • Lake Erie Medical and Surgical Supply
  • Murfreesboro Pharmaceutical Nursing Supply
  • Mylan
  • Nucare Pharmaceuticals Inc.
  • Palmetto Pharmaceuticals Inc.
  • PD-Rx Pharmaceuticals Inc.
  • Physicians Total Care Inc.
  • Prepackage Specialists
  • Prepak Systems Inc.
  • Rebel Distributors Corp.
  • Remedy Repack
  • Resource Optimization and Innovation LLC
  • Schwarz Pharma Inc.
  • Southwood Pharmaceuticals
  • Stat Rx Usa
  • Teva Pharmaceutical Industries Ltd.
  • Tya Pharmaceuticals
  • UDL Laboratories
  • Upstate Pharma LLC
  • Vangard Labs Inc.
  • Wyeth Pharmaceuticals
  • Zydus Pharmaceuticals
Dosage Forms
FormRouteStrength
CapsuleOral75.000 mg
CapsuleOral75.000 mg
CapsuleOral
Capsule, delayed releaseOral150 mg
Capsule, delayed releaseOral75 mg
Capsule, extended releaseOral
TabletOral25 MG
Capsule, extended releaseOral84.85 MG
Capsule, extended releaseOral150 mg
Capsule, coated pellets150 mg
Capsule, coated pellets37.5 mg
Capsule, extended releaseOral37.5 mg
CapsuleOral37.5 MG
Capsule, coated pellets75 mg
Capsule, extended releaseOral75 mg
CapsuleOral150 mg
CapsuleOral75 mg
TabletOral50 mg/1
TabletOral75 mg/1
TabletOral37.5 mg
TabletOral50 mg
TabletOral75 mg
Capsule, extended releaseOral150 mg/1
Capsule, extended releaseOral37.5 mg/1
Capsule, extended releaseOral75 mg/1
TabletOral150.000 mg
CapsuleOral42.429 mg
Tablet, film coated, extended releaseOral
Tablet, film coated, extended releaseOral75 mg
CapsuleOral169.724 mg
Tablet, coatedOral75 mg
TabletOral50.00 mg
CapsuleOral84.850 mg
CapsuleOral75.00 mg
CapsuleOral
Capsule, extended releaseOral225 MG
Tablet, extended releaseOral225 MG
Tablet, film coatedOral37.5 MG
Tablet, film coatedOral75 MG
TabletOral
Tablet, extended releaseOral37.5 mg
Tablet, extended releaseOral300 mg
SolutionOral
Tablet, extended releaseOral
Tablet, coatedOral150 mg/1
Tablet, coatedOral225 mg/1
Tablet, coatedOral75 mg/1
Tablet, extended releaseOral112.5 mg/1
Tablet, extended releaseOral150 mg/1
Tablet, extended releaseOral225 mg/1
Tablet, extended releaseOral37.5 mg/1
Tablet, extended releaseOral75 mg/1
Capsule, delayed releaseOral75 mg/1
TabletOral100 mg/1
TabletOral150 mg/1
TabletOral225 mg/1
TabletOral25 mg/1
TabletOral37.5 mg/1
Tablet, film coatedOral100 mg/1
Tablet, film coatedOral25 mg/1
Tablet, film coatedOral37.5 mg/1
Tablet, film coatedOral50 mg/1
Tablet, film coatedOral75 mg/1
Tablet, film coated, extended releaseOral150 mg/1
Tablet, film coated, extended releaseOral225 mg/1
Tablet, film coated, extended releaseOral37.5 mg/1
Tablet, film coated, extended releaseOral75 mg/1
Capsule, extended releaseOral150.0 mg
Capsule, extended releaseOral75.0 mg
CapsuleOral37.50 mg
Tablet, extended releaseOral150 mg
Tablet, extended releaseOral75 mg
CapsuleOral42.430 mg
SolutionOral75 MG/ML
Prices
Unit descriptionCostUnit
Venlafaxine HCl 30 225 mg 24 Hour tablet Bottle276.98USD bottle
Effexor XR 30 37.5 mg 24 Hour Capsule Bottle144.33USD bottle
Venlafaxine HCl 30 37.5 mg 24 Hour tablet Bottle114.46USD bottle
Effexor 30 75 mg tablet Bottle87.83USD bottle
Effexor 30 25 mg tablet Bottle74.82USD bottle
Effexor XR 150 mg 24 Hour Capsule5.87USD capsule
Effexor xr 150 mg capsule5.65USD capsule
Effexor XR 75 mg 24 Hour Capsule5.39USD capsule
Effexor xr 75 mg capsule4.76USD capsule
Venlafaxine HCl 150 mg 24 Hour tablet4.72USD tablet
Effexor xr 37.5 mg capsule4.63USD capsule
Venlafaxine HCl 75 mg 24 Hour tablet4.42USD tablet
Effexor 100 mg tablet2.92USD tablet
Effexor 75 mg tablet2.7USD tablet
Effexor 50 mg tablet2.6USD tablet
Effexor 37.5 mg tablet2.5USD tablet
Effexor 25 mg tablet2.4USD tablet
Venlafaxine hcl 100 mg tablet2.36USD tablet
Venlafaxine hcl 75 mg tablet2.23USD tablet
Effexor Xr 150 mg Extended-Release Capsule2.16USD capsule
Venlafaxine hcl 50 mg tablet2.1USD tablet
Effexor Xr 75 mg Extended-Release Capsule2.05USD capsule
Venlafaxine hcl 37.5 mg tablet2.04USD tablet
Venlafaxine hcl 25 mg tablet1.98USD tablet
Apo-Venlafaxine Xr 150 mg Extended-Release Capsule1.2USD capsule
Co Venlafaxine Xr 150 mg Extended-Release Capsule1.2USD capsule
Mylan-Venlafaxine Xr 150 mg Extended-Release Capsule1.2USD capsule
Novo-Venlafaxine Xr 150 mg Extended-Release Capsule1.2USD capsule
Pms-Venlafaxine Xr 150 mg Extended-Release Capsule1.2USD capsule
Ratio-Venlafaxine Xr 150 mg Extended-Release Capsule1.2USD capsule
Sandoz Venlafaxine Xr 150 mg Extended-Release Capsule1.2USD capsule
Apo-Venlafaxine Xr 75 mg Extended-Release Capsule1.14USD capsule
Co Venlafaxine Xr 75 mg Extended-Release Capsule1.14USD capsule
Mylan-Venlafaxine Xr 75 mg Extended-Release Capsule1.14USD capsule
Novo-Venlafaxine Xr 75 mg Extended-Release Capsule1.14USD capsule
Pms-Venlafaxine Xr 75 mg Extended-Release Capsule1.14USD capsule
Ratio-Venlafaxine Xr 75 mg Extended-Release Capsule1.14USD capsule
Sandoz Venlafaxine Xr 75 mg Extended-Release Capsule1.14USD capsule
Effexor Xr 37.5 mg Extended-Release Capsule1.02USD capsule
Apo-Venlafaxine Xr 37.5 mg Extended-Release Capsule0.57USD capsule
Co Venlafaxine Xr 37.5 mg Extended-Release Capsule0.57USD capsule
Mylan-Venlafaxine Xr 37.5 mg Extended-Release Capsule0.57USD capsule
Novo-Venlafaxine Xr 37.5 mg Extended-Release Capsule0.57USD capsule
Pms-Venlafaxine Xr 37.5 mg Extended-Release Capsule0.57USD capsule
Ratio-Venlafaxine Xr 37.5 mg Extended-Release Capsule0.57USD capsule
Sandoz Venlafaxine Xr 37.5 mg Extended-Release Capsule0.57USD capsule
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)Region
US5916923No1999-06-292013-06-28US flag
CA2126305No2006-10-172014-06-20Canada flag
CA2199778No2005-12-202017-03-12Canada flag
US6403120Yes2002-06-112017-09-20US flag
US6419958Yes2002-07-162017-09-20US flag
US6274171Yes2001-08-142017-09-20US flag
US6717015No2004-04-062023-03-27US flag
US7776358No2010-08-172028-05-16US flag

Properties

State
Solid
Experimental Properties
PropertyValueSource
water solubility572 mg/mLhttps://www.accessdata.fda.gov/drugsatfda_docs/label/2022/020699s112lbl.pdf
Predicted Properties
PropertyValueSource
Water Solubility0.23 mg/mLALOGPS
logP2.69ALOGPS
logP2.74Chemaxon
logS-3.1ALOGPS
pKa (Strongest Acidic)14.42Chemaxon
pKa (Strongest Basic)8.91Chemaxon
Physiological Charge1Chemaxon
Hydrogen Acceptor Count3Chemaxon
Hydrogen Donor Count1Chemaxon
Polar Surface Area32.7 Å2Chemaxon
Rotatable Bond Count5Chemaxon
Refractivity83.02 m3·mol-1Chemaxon
Polarizability32.33 Å3Chemaxon
Number of Rings2Chemaxon
Bioavailability1Chemaxon
Rule of FiveYesChemaxon
Ghose FilterYesChemaxon
Veber's RuleYesChemaxon
MDDR-like RuleNoChemaxon
Predicted ADMET Features
PropertyValueProbability
Human Intestinal Absorption+0.9782
Blood Brain Barrier+0.9382
Caco-2 permeable+0.852
P-glycoprotein substrateSubstrate0.6534
P-glycoprotein inhibitor IInhibitor0.7031
P-glycoprotein inhibitor IIInhibitor0.8031
Renal organic cation transporterNon-inhibitor0.5792
CYP450 2C9 substrateNon-substrate0.7583
CYP450 2D6 substrateSubstrate0.8919
CYP450 3A4 substrateSubstrate0.7407
CYP450 1A2 substrateNon-inhibitor0.7664
CYP450 2C9 inhibitorNon-inhibitor0.6876
CYP450 2D6 inhibitorInhibitor0.7287
CYP450 2C19 inhibitorNon-inhibitor0.7199
CYP450 3A4 inhibitorNon-inhibitor0.8308
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.8666
Ames testNon AMES toxic0.8
CarcinogenicityNon-carcinogens0.6762
BiodegradationNot ready biodegradable0.9941
Rat acute toxicity2.5404 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.5486
hERG inhibition (predictor II)Inhibitor0.6627
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSsplash10-0a4i-9110000000-10fdc1f0eb77f9e8ed4e
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-004i-0090000000-d413fb5f16658fcc5acb
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-004i-0090000000-182f1032c3f72220679d
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-00dj-0910000000-c7a4a25a9bc95faa6db1
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-00di-0900000000-7be3d65db3af35be404e
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-00di-0900000000-615322444dcf11a7fb8d
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-03di-0090000000-d212108d9a8267ed7dad
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-004i-0090000000-0c4e12d13e69311b26bf
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0bvi-4090000000-8bf2805a95084bfd952a
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0a4i-9520000000-de599153aa118f97ad81
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0ab9-8900000000-6e9f54b654899b486e4d
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0ab9-9800000000-d762b2d7edeba1e12b28
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0ab9-9700000000-2b8ebcefcf1274550d32
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-004i-0090000000-c592b4ae2ead9b2bb7ea
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0bvi-4090000000-30b9b5dca017215ebaa4
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0a4i-9620000000-ab905f15470a13b750c5
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0ab9-8900000000-52ec7a86d35dbbd47681
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0ab9-9800000000-7a7cc5b11e1a30499063
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-0ab9-9700000000-062f05f9fe2a1540985c
LC-MS/MS Spectrum - LC-ESI-ITFT , positiveLC-MS/MSsplash10-03di-0090000000-8eb971c1dc9a14696c31
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-01t9-2090000000-af607e34f7f6700231a4
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0a4i-9140000000-0b22aeda0f56bf825768
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0a4i-9300000000-f28ae1a2451e218836c6
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0a4i-9400000000-c36a2f70d6d9fd69dbfe
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0a4i-9500000000-43a71bea54c5b09c4c9a
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0a4i-9400000000-9763935e9812b45adddb
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-0bvi-6090000000-fabb5e8a0fd59b8420ca
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-0a4i-9100000000-b67e5a7dbbd83cf2a7a7
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-0a4i-9200000000-2300decf19900a1b84e4
MS/MS Spectrum - Linear Ion Trap , positiveLC-MS/MSsplash10-03di-0090000000-40f0dac6b8ca62d0314f
MS/MS Spectrum - , positiveLC-MS/MSsplash10-01t9-0390000000-7a760936fedd0f48cebf
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0a4i-9260000000-0b8e3be9620e0271d683
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-01t9-2090000000-94fb4781a9910b6b1932
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0a4i-9140000000-e2c800f5f39f048c545a
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0a4i-9400000000-e0fa4c4197355be8d0fa
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0a4i-9500000000-23cbb70f5d3c368966bb
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0a4i-9500000000-998e2271dd7ac0572d54
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSsplash10-056r-3190000000-959128d1f6580977f95f
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSsplash10-002f-0590000000-f062baff8daad006a867
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSsplash10-0a4i-9020000000-f455bf46aca42a5601a0
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSsplash10-0v09-1590000000-c3755e5421d065184b41
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSsplash10-0a4i-9120000000-01d8c29e105046cb37fd
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSsplash10-0i00-4590000000-2b68831503430e6251f5
1H NMR Spectrum1D NMRNot Applicable
Predicted 1H NMR Spectrum1D NMRNot Applicable
Predicted 13C NMR Spectrum1D NMRNot Applicable
[1H,13C] 2D NMR Spectrum2D NMRNot Applicable
Chromatographic Properties
Collision Cross Sections (CCS)
AdductCCS Value (Å2)Source typeSource
[M-H]-178.5903564
predicted
DarkChem Lite v0.1.0
[M-H]-178.1703564
predicted
DarkChem Lite v0.1.0
[M-H]-167.74342
predicted
DeepCCS 1.0 (2019)
[M+H]+178.6951564
predicted
DarkChem Lite v0.1.0
[M+H]+178.6077564
predicted
DarkChem Lite v0.1.0
[M+H]+170.10143
predicted
DeepCCS 1.0 (2019)
[M+Na]+178.5258564
predicted
DarkChem Lite v0.1.0
[M+Na]+178.4840564
predicted
DarkChem Lite v0.1.0
[M+Na]+176.19458
predicted
DeepCCS 1.0 (2019)

Targets

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Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
Curator comments
K(i)=82nM
General Function
Serotonin transporter that cotransports serotonin with one Na(+) ion in exchange for one K(+) ion and possibly one proton in an overall electroneutral transport cycle. Transports serotonin across the plasma membrane from the extracellular compartment to the cytosol thus limiting serotonin intercellular signaling (PubMed:10407194, PubMed:12869649, PubMed:21730057, PubMed:27049939, PubMed:27756841, PubMed:34851672). Essential for serotonin homeostasis in the central nervous system. In the developing somatosensory cortex, acts in glutamatergic neurons to control serotonin uptake and its trophic functions accounting for proper spatial organization of cortical neurons and elaboration of sensory circuits. In the mature cortex, acts primarily in brainstem raphe neurons to mediate serotonin uptake from the synaptic cleft back into the pre-synaptic terminal thus terminating serotonin signaling at the synapse (By similarity). Modulates mucosal serotonin levels in the gastrointestinal tract through uptake and clearance of serotonin in enterocytes. Required for enteric neurogenesis and gastrointestinal reflexes (By similarity). Regulates blood serotonin levels by ensuring rapid high affinity uptake of serotonin from plasma to platelets, where it is further stored in dense granules via vesicular monoamine transporters and then released upon stimulation (PubMed:17506858, PubMed:18317590). Mechanistically, the transport cycle starts with an outward-open conformation having Na1(+) and Cl(-) sites occupied. The binding of a second extracellular Na2(+) ion and serotonin substrate leads to structural changes to outward-occluded to inward-occluded to inward-open, where the Na2(+) ion and serotonin are released into the cytosol. Binding of intracellular K(+) ion induces conformational transitions to inward-occluded to outward-open and completes the cycle by releasing K(+) possibly together with a proton bound to Asp-98 into the extracellular compartment. Na1(+) and Cl(-) ions remain bound throughout the transport cycle (PubMed:10407194, PubMed:12869649, PubMed:21730057, PubMed:27049939, PubMed:27756841, PubMed:34851672). Additionally, displays serotonin-induced channel-like conductance for monovalent cations, mainly Na(+) ions. The channel activity is uncoupled from the transport cycle and may contribute to the membrane resting potential or excitability (By similarity)
Specific Function
actin filament binding
Gene Name
SLC6A4
Uniprot ID
P31645
Uniprot Name
Sodium-dependent serotonin transporter
Molecular Weight
70324.165 Da
References
  1. Chen F, Larsen MB, Sanchez C, Wiborg O: The S-enantiomer of R,S-citalopram, increases inhibitor binding to the human serotonin transporter by an allosteric mechanism. Comparison with other serotonin transporter inhibitors. Eur Neuropsychopharmacol. 2005 Mar;15(2):193-8. [Article]
  2. Gould GG, Altamirano AV, Javors MA, Frazer A: A comparison of the chronic treatment effects of venlafaxine and other antidepressants on serotonin and norepinephrine transporters. Biol Psychiatry. 2006 Mar 1;59(5):408-14. Epub 2005 Sep 2. [Article]
  3. Shang Y, Gibbs MA, Marek GJ, Stiger T, Burstein AH, Marek K, Seibyl JP, Rogers JF: Displacement of serotonin and dopamine transporters by venlafaxine extended release capsule at steady state: a [123I]2beta-carbomethoxy-3beta-(4-iodophenyl)-tropane single photon emission computed tomography imaging study. J Clin Psychopharmacol. 2007 Feb;27(1):71-5. [Article]
  4. Malizia AL, Melichar JM, Brown DJ, Gunn RN, Reynolds A, Jones T, Nutt DJ: Demonstration of clomipramine and venlafaxine occupation at serotonin reuptake sites in man in vivo. J Psychopharmacol. 1997;11(3):279-81. [Article]
  5. Tatsumi M, Groshan K, Blakely RD, Richelson E: Pharmacological profile of antidepressants and related compounds at human monoamine transporters. Eur J Pharmacol. 1997 Dec 11;340(2-3):249-58. [Article]
  6. Van Ameringen M, Mancini C, Patterson B, Simpson W: Pharmacotherapy for social anxiety disorder: an update. Isr J Psychiatry Relat Sci. 2009;46(1):53-61. [Article]
  7. Beique J, de Montigny C, Blier P, Debonnel G: Effects of sustained administration of the serotonin and norepinephrine reuptake inhibitor venlafaxine: I. in vivo electrophysiological studies in the rat. Neuropharmacology. 2000 Jul 24;39(10):1800-12. [Article]
  8. Westenberg HG: Recent advances in understanding and treating social anxiety disorder. CNS Spectr. 2009 Feb;14(2 Suppl 3):24-33. [Article]
  9. Sindrup SH, Otto M, Finnerup NB, Jensen TS: Antidepressants in the treatment of neuropathic pain. Basic Clin Pharmacol Toxicol. 2005 Jun;96(6):399-409. [Article]
  10. Bymaster FP, Dreshfield-Ahmad LJ, Threlkeld PG, Shaw JL, Thompson L, Nelson DL, Hemrick-Luecke SK, Wong DT: Comparative affinity of duloxetine and venlafaxine for serotonin and norepinephrine transporters in vitro and in vivo, human serotonin receptor subtypes, and other neuronal receptors. Neuropsychopharmacology. 2001 Dec;25(6):871-80. [Article]
  11. Zhou Y, Zhang Y, Zhao D, Yu X, Shen X, Zhou Y, Wang S, Qiu Y, Chen Y, Zhu F: TTD: Therapeutic Target Database describing target druggability information. Nucleic Acids Res. 2024 Jan 5;52(D1):D1465-D1477. doi: 10.1093/nar/gkad751. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
Curator comments
K(i)=2480nM
General Function
Mediates sodium- and chloride-dependent transport of norepinephrine (also known as noradrenaline) (PubMed:2008212, PubMed:8125921). Can also mediate sodium- and chloride-dependent transport of dopamine (PubMed:11093780, PubMed:8125921)
Specific Function
actin binding
Gene Name
SLC6A2
Uniprot ID
P23975
Uniprot Name
Sodium-dependent noradrenaline transporter
Molecular Weight
69331.42 Da
References
  1. Vaishnavi SN, Nemeroff CB, Plott SJ, Rao SG, Kranzler J, Owens MJ: Milnacipran: a comparative analysis of human monoamine uptake and transporter binding affinity. Biol Psychiatry. 2004 Feb 1;55(3):320-2. [Article]
  2. Mitchell HA, Ahern TH, Liles LC, Javors MA, Weinshenker D: The effects of norepinephrine transporter inactivation on locomotor activity in mice. Biol Psychiatry. 2006 Nov 15;60(10):1046-52. Epub 2006 Aug 7. [Article]
  3. Beique JC, Lavoie N, de Montigny C, Debonnel G: Affinities of venlafaxine and various reuptake inhibitors for the serotonin and norepinephrine transporters. Eur J Pharmacol. 1998 May 15;349(1):129-32. [Article]
  4. Van Ameringen M, Mancini C, Patterson B, Simpson W: Pharmacotherapy for social anxiety disorder: an update. Isr J Psychiatry Relat Sci. 2009;46(1):53-61. [Article]
  5. Beique J, de Montigny C, Blier P, Debonnel G: Effects of sustained administration of the serotonin and norepinephrine reuptake inhibitor venlafaxine: I. in vivo electrophysiological studies in the rat. Neuropharmacology. 2000 Jul 24;39(10):1800-12. [Article]
  6. Westenberg HG: Recent advances in understanding and treating social anxiety disorder. CNS Spectr. 2009 Feb;14(2 Suppl 3):24-33. [Article]
  7. Sindrup SH, Otto M, Finnerup NB, Jensen TS: Antidepressants in the treatment of neuropathic pain. Basic Clin Pharmacol Toxicol. 2005 Jun;96(6):399-409. [Article]
  8. Bymaster FP, Dreshfield-Ahmad LJ, Threlkeld PG, Shaw JL, Thompson L, Nelson DL, Hemrick-Luecke SK, Wong DT: Comparative affinity of duloxetine and venlafaxine for serotonin and norepinephrine transporters in vitro and in vivo, human serotonin receptor subtypes, and other neuronal receptors. Neuropsychopharmacology. 2001 Dec;25(6):871-80. [Article]
  9. Zhou Y, Zhang Y, Zhao D, Yu X, Shen X, Zhou Y, Wang S, Qiu Y, Chen Y, Zhu F: TTD: Therapeutic Target Database describing target druggability information. Nucleic Acids Res. 2024 Jan 5;52(D1):D1465-D1477. doi: 10.1093/nar/gkad751. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Mediates sodium- and chloride-dependent transport of dopamine (PubMed:10375632, PubMed:11093780, PubMed:1406597, PubMed:15505207, PubMed:19478460, PubMed:8302271). Also mediates sodium- and chloride-dependent transport of norepinephrine (also known as noradrenaline) (By similarity). Regulator of light-dependent retinal hyaloid vessel regression, downstream of OPN5 signaling (By similarity)
Specific Function
amine binding
Gene Name
SLC6A3
Uniprot ID
Q01959
Uniprot Name
Sodium-dependent dopamine transporter
Molecular Weight
68494.255 Da
References
  1. Dawson LA, Nguyen HQ, Geiger A: Effects of venlafaxine on extracellular concentrations of 5-HT and noradrenaline in the rat frontal cortex: augmentation via 5-HT1A receptor antagonism. Neuropharmacology. 1999 Aug;38(8):1153-63. [Article]
  2. Bourin M: [Psychopharmacological profile of venlafaxine]. Encephale. 1999 Jun;25 Spec No 2:21-2; discussion 23-5. [Article]
  3. Barkin RL, Fawcett J: The management challenges of chronic pain: the role of antidepressants. Am J Ther. 2000 Jan;7(1):31-47. [Article]
  4. Lemke MR: [Antidepressant effects of dopamine agonists. Experimental and clinical findings]. Nervenarzt. 2007 Jan;78(1):31-8. [Article]

Enzymes

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
A cytochrome P450 monooxygenase involved in the metabolism of fatty acids, steroids and retinoids (PubMed:18698000, PubMed:19965576, PubMed:20972997, PubMed:21289075, PubMed:21576599). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase) (PubMed:18698000, PubMed:19965576, PubMed:20972997, PubMed:21289075, PubMed:21576599). Catalyzes the epoxidation of double bonds of polyunsaturated fatty acids (PUFA) (PubMed:19965576, PubMed:20972997). Metabolizes endocannabinoid arachidonoylethanolamide (anandamide) to 20-hydroxyeicosatetraenoic acid ethanolamide (20-HETE-EA) and 8,9-, 11,12-, and 14,15-epoxyeicosatrienoic acid ethanolamides (EpETrE-EAs), potentially modulating endocannabinoid system signaling (PubMed:18698000, PubMed:21289075). Catalyzes the hydroxylation of carbon-hydrogen bonds. Metabolizes cholesterol toward 25-hydroxycholesterol, a physiological regulator of cellular cholesterol homeostasis (PubMed:21576599). Catalyzes the oxidative transformations of all-trans retinol to all-trans retinal, a precursor for the active form all-trans-retinoic acid (PubMed:10681376). Also involved in the oxidative metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic antidepressants
Specific Function
anandamide 11,12 epoxidase activity
Gene Name
CYP2D6
Uniprot ID
P10635
Uniprot Name
Cytochrome P450 2D6
Molecular Weight
55768.94 Da
References
  1. Fogelman SM, Schmider J, Venkatakrishnan K, von Moltke LL, Harmatz JS, Shader RI, Greenblatt DJ: O- and N-demethylation of venlafaxine in vitro by human liver microsomes and by microsomes from cDNA-transfected cells: effect of metabolic inhibitors and SSRI antidepressants. Neuropsychopharmacology. 1999 May;20(5):480-90. [Article]
  2. Lin XQ, Wang P, Cai WK, Xu GL, Yang M, Zhou MD, Sun M, He F, He GH: The Associations Between CYP2D6 Metabolizer Status and Pharmacokinetics and Clinical Outcomes of Venlafaxine: A Systematic Review and Meta-Analysis. Pharmacopsychiatry. 2018 Nov 28. doi: 10.1055/a-0792-1340. [Article]
  3. Flockhart Table of Drug Interactions [Link]
  4. FDA Approved Drug Products: EFFEXOR XR (venlafaxine extended-release) capsules, for oral use (August 2022) [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
A cytochrome P450 monooxygenase involved in the metabolism of sterols, steroid hormones, retinoids and fatty acids (PubMed:10681376, PubMed:11093772, PubMed:11555828, PubMed:12865317, PubMed:14559847, PubMed:15373842, PubMed:15764715, PubMed:19965576, PubMed:20702771, PubMed:21490593, PubMed:21576599). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase). Catalyzes the hydroxylation of carbon-hydrogen bonds (PubMed:12865317, PubMed:14559847, PubMed:15373842, PubMed:15764715, PubMed:21490593, PubMed:21576599, PubMed:2732228). Exhibits high catalytic activity for the formation of hydroxyestrogens from estrone (E1) and 17beta-estradiol (E2), namely 2-hydroxy E1 and E2, as well as D-ring hydroxylated E1 and E2 at the C-16 position (PubMed:11555828, PubMed:12865317, PubMed:14559847). Plays a role in the metabolism of androgens, particularly in oxidative deactivation of testosterone (PubMed:15373842, PubMed:15764715, PubMed:22773874, PubMed:2732228). Metabolizes testosterone to less biologically active 2beta- and 6beta-hydroxytestosterones (PubMed:15373842, PubMed:15764715, PubMed:2732228). Contributes to the formation of hydroxycholesterols (oxysterols), particularly A-ring hydroxylated cholesterol at the C-4beta position, and side chain hydroxylated cholesterol at the C-25 position, likely contributing to cholesterol degradation and bile acid biosynthesis (PubMed:21576599). Catalyzes bisallylic hydroxylation of polyunsaturated fatty acids (PUFA) (PubMed:9435160). Catalyzes the epoxidation of double bonds of PUFA with a preference for the last double bond (PubMed:19965576). Metabolizes endocannabinoid arachidonoylethanolamide (anandamide) to 8,9-, 11,12-, and 14,15-epoxyeicosatrienoic acid ethanolamides (EpETrE-EAs), potentially modulating endocannabinoid system signaling (PubMed:20702771). Plays a role in the metabolism of retinoids. Displays high catalytic activity for oxidation of all-trans-retinol to all-trans-retinal, a rate-limiting step for the biosynthesis of all-trans-retinoic acid (atRA) (PubMed:10681376). Further metabolizes atRA toward 4-hydroxyretinoate and may play a role in hepatic atRA clearance (PubMed:11093772). Responsible for oxidative metabolism of xenobiotics. Acts as a 2-exo-monooxygenase for plant lipid 1,8-cineole (eucalyptol) (PubMed:11159812). Metabolizes the majority of the administered drugs. Catalyzes sulfoxidation of the anthelmintics albendazole and fenbendazole (PubMed:10759686). Hydroxylates antimalarial drug quinine (PubMed:8968357). Acts as a 1,4-cineole 2-exo-monooxygenase (PubMed:11695850). Also involved in vitamin D catabolism and calcium homeostasis. Catalyzes the inactivation of the active hormone calcitriol (1-alpha,25-dihydroxyvitamin D(3)) (PubMed:29461981)
Specific Function
1,8-cineole 2-exo-monooxygenase activity
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. [Article]
  2. Otton SV, Ball SE, Cheung SW, Inaba T, Rudolph RL, Sellers EM: Venlafaxine oxidation in vitro is catalysed by CYP2D6. Br J Clin Pharmacol. 1996 Feb;41(2):149-56. [Article]
  3. Ciusani E, Zullino DF, Eap CB, Brawand-Amey M, Brocard M, Baumann P: Combination therapy with venlafaxine and carbamazepine in depressive patients not responding to venlafaxine: pharmacokinetic and clinical aspects. J Psychopharmacol. 2004 Dec;18(4):559-66. doi: 10.1177/026988110401800414. [Article]
  4. FDA Approved Drug Products: EFFEXOR XR (venlafaxine extended-release) capsules, for oral use (August 2022) [Link]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
General Function
A cytochrome P450 monooxygenase involved in the metabolism of various endogenous substrates, including fatty acids and steroids (PubMed:12865317, PubMed:15766564, PubMed:19965576, PubMed:21576599, PubMed:7574697, PubMed:9435160, PubMed:9866708). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase) (PubMed:12865317, PubMed:15766564, PubMed:19965576, PubMed:21576599, PubMed:7574697, PubMed:9435160, PubMed:9866708). Catalyzes the epoxidation of double bonds of polyunsaturated fatty acids (PUFA) (PubMed:15766564, PubMed:19965576, PubMed:7574697, PubMed:9866708). Catalyzes the hydroxylation of carbon-hydrogen bonds. Metabolizes cholesterol toward 25-hydroxycholesterol, a physiological regulator of cellular cholesterol homeostasis (PubMed:21576599). Exhibits low catalytic activity for the formation of catechol estrogens from 17beta-estradiol (E2) and estrone (E1), namely 2-hydroxy E1 and E2 (PubMed:12865317). Catalyzes bisallylic hydroxylation and hydroxylation with double-bond migration of polyunsaturated fatty acids (PUFA) (PubMed:9435160, PubMed:9866708). Also metabolizes plant monoterpenes such as limonene. Oxygenates (R)- and (S)-limonene to produce carveol and perillyl alcohol (PubMed:11950794). Contributes to the wide pharmacokinetics variability of the metabolism of drugs such as S-warfarin, diclofenac, phenytoin, tolbutamide and losartan (PubMed:25994031)
Specific Function
(R)-limonene 6-monooxygenase activity
Gene Name
CYP2C9
Uniprot ID
P11712
Uniprot Name
Cytochrome P450 2C9
Molecular Weight
55627.365 Da
References
  1. Fogelman SM, Schmider J, Venkatakrishnan K, von Moltke LL, Harmatz JS, Shader RI, Greenblatt DJ: O- and N-demethylation of venlafaxine in vitro by human liver microsomes and by microsomes from cDNA-transfected cells: effect of metabolic inhibitors and SSRI antidepressants. Neuropsychopharmacology. 1999 May;20(5):480-90. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
No
Actions
Substrate
General Function
A cytochrome P450 monooxygenase involved in the metabolism of polyunsaturated fatty acids (PUFA) (PubMed:18577768, PubMed:19965576, PubMed:20972997). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate, and reducing the second into a water molecule, with two electrons provided by NADPH via cytochrome P450 reductase (NADPH--hemoprotein reductase) (PubMed:18577768, PubMed:19965576, PubMed:20972997). Catalyzes the hydroxylation of carbon-hydrogen bonds. Hydroxylates PUFA specifically at the omega-1 position (PubMed:18577768). Catalyzes the epoxidation of double bonds of PUFA (PubMed:19965576, PubMed:20972997). Also metabolizes plant monoterpenes such as limonene. Oxygenates (R)- and (S)-limonene to produce carveol and perillyl alcohol (PubMed:11950794). Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and imipramine. Hydroxylates fenbendazole at the 4' position (PubMed:23959307)
Specific Function
(R)-limonene 6-monooxygenase activity
Gene Name
CYP2C19
Uniprot ID
P33261
Uniprot Name
Cytochrome P450 2C19
Molecular Weight
55944.565 Da
References
  1. Fogelman SM, Schmider J, Venkatakrishnan K, von Moltke LL, Harmatz JS, Shader RI, Greenblatt DJ: O- and N-demethylation of venlafaxine in vitro by human liver microsomes and by microsomes from cDNA-transfected cells: effect of metabolic inhibitors and SSRI antidepressants. Neuropsychopharmacology. 1999 May;20(5):480-90. [Article]

Transporters

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Translocates drugs and phospholipids across the membrane (PubMed:2897240, PubMed:35970996, PubMed:8898203, PubMed:9038218). Catalyzes the flop of phospholipids from the cytoplasmic to the exoplasmic leaflet of the apical membrane. Participates mainly to the flop of phosphatidylcholine, phosphatidylethanolamine, beta-D-glucosylceramides and sphingomyelins (PubMed:8898203). Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells (PubMed:2897240, PubMed:35970996, PubMed:9038218)
Specific Function
ABC-type xenobiotic transporter activity
Gene Name
ABCB1
Uniprot ID
P08183
Uniprot Name
ATP-dependent translocase ABCB1
Molecular Weight
141477.255 Da
References
  1. Weiss J, Dormann SM, Martin-Facklam M, Kerpen CJ, Ketabi-Kiyanvash N, Haefeli WE: Inhibition of P-glycoprotein by newer antidepressants. J Pharmacol Exp Ther. 2003 Apr;305(1):197-204. [Article]
  2. Uhr M, Grauer MT, Holsboer F: Differential enhancement of antidepressant penetration into the brain in mice with abcb1ab (mdr1ab) P-glycoprotein gene disruption. Biol Psychiatry. 2003 Oct 15;54(8):840-6. [Article]
  3. Karlsson L, Schmitt U, Josefsson M, Carlsson B, Ahlner J, Bengtsson F, Kugelberg FC, Hiemke C: Blood-brain barrier penetration of the enantiomers of venlafaxine and its metabolites in mice lacking P-glycoprotein. Eur Neuropsychopharmacol. 2010 Sep;20(9):632-40. doi: 10.1016/j.euroneuro.2010.04.004. Epub 2010 May 13. [Article]
  4. Bachmeier CJ, Beaulieu-Abdelahad D, Ganey NJ, Mullan MJ, Levin GM: Induction of drug efflux protein expression by venlafaxine but not desvenlafaxine. Biopharm Drug Dispos. 2011 May;32(4):233-44. doi: 10.1002/bdd.753. Epub 2011 Mar 28. [Article]
  5. Zhou Y, Zhang G, Rao Z, Yang Y, Zhou Q, Qin H, Wei Y, Wu X: Increased brain uptake of venlafaxine loaded solid lipid nanoparticles by overcoming the efflux function and expression of P-gp. Arch Pharm Res. 2015 Jul;38(7):1325-35. doi: 10.1007/s12272-014-0539-6. Epub 2015 Jan 8. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inducer
General Function
Broad substrate specificity ATP-dependent transporter of the ATP-binding cassette (ABC) family that actively extrudes a wide variety of physiological compounds, dietary toxins and xenobiotics from cells (PubMed:11306452, PubMed:12958161, PubMed:19506252, PubMed:20705604, PubMed:28554189, PubMed:30405239, PubMed:31003562). Involved in porphyrin homeostasis, mediating the export of protoporphyrin IX (PPIX) from both mitochondria to cytosol and cytosol to extracellular space, it also functions in the cellular export of heme (PubMed:20705604, PubMed:23189181). Also mediates the efflux of sphingosine-1-P from cells (PubMed:20110355). Acts as a urate exporter functioning in both renal and extrarenal urate excretion (PubMed:19506252, PubMed:20368174, PubMed:22132962, PubMed:31003562, PubMed:36749388). In kidney, it also functions as a physiological exporter of the uremic toxin indoxyl sulfate (By similarity). Also involved in the excretion of steroids like estrone 3-sulfate/E1S, 3beta-sulfooxy-androst-5-en-17-one/DHEAS, and other sulfate conjugates (PubMed:12682043, PubMed:28554189, PubMed:30405239). Mediates the secretion of the riboflavin and biotin vitamins into milk (By similarity). Extrudes pheophorbide a, a phototoxic porphyrin catabolite of chlorophyll, reducing its bioavailability (By similarity). Plays an important role in the exclusion of xenobiotics from the brain (Probable). It confers to cells a resistance to multiple drugs and other xenobiotics including mitoxantrone, pheophorbide, camptothecin, methotrexate, azidothymidine, and the anthracyclines daunorubicin and doxorubicin, through the control of their efflux (PubMed:11306452, PubMed:12477054, PubMed:15670731, PubMed:18056989, PubMed:31254042). In placenta, it limits the penetration of drugs from the maternal plasma into the fetus (By similarity). May play a role in early stem cell self-renewal by blocking differentiation (By similarity)
Specific Function
ABC-type xenobiotic transporter activity
Gene Name
ABCG2
Uniprot ID
Q9UNQ0
Uniprot Name
Broad substrate specificity ATP-binding cassette transporter ABCG2
Molecular Weight
72313.47 Da
References
  1. Bachmeier CJ, Beaulieu-Abdelahad D, Ganey NJ, Mullan MJ, Levin GM: Induction of drug efflux protein expression by venlafaxine but not desvenlafaxine. Biopharm Drug Dispos. 2011 May;32(4):233-44. doi: 10.1002/bdd.753. Epub 2011 Mar 28. [Article]

Drug created at June 13, 2005 13:24 / Updated at October 07, 2024 17:26