Venlafaxine
drugOn this page
Also known as Alventa xlAmphero xlBonilux xlDepefex xlEfectinEfexorEfexor xlForaven xlKanghongMentaven xlNSC-758676Politid xlRanfaxine xlRodomel xlSunveniz xlTardcaps xlTifaxin xlTonpular xlTrevilorTrixat xl
Summary
Venlafaxine (CHEMBL637) is an approved small-molecule antidepressant (ATC N06AX16) targeting SLC6A2 and SLC6A4; indicated across 2 conditions including depressive disorder.
At a glance
- Status: Approved (max clinical phase 4)
- Modality: Small molecule
- ATC class: N06AX16
- Targets: 2 (SLC6A2, SLC6A4)
- Indications: 2 conditions
- Clinical trials: 114
- Chemistry: 277.4 Da · C17H27NO2
Identifiers
Drug identity and classification
| Field | Value |
|---|---|
| ChEMBL ID | CHEMBL637 |
| Name | Venlafaxine |
| Type | Small molecule |
| Max phase | 4 |
| FDA approved | yes |
| PubChem CID | 5656 |
| ChEBI | CHEBI:9943 |
| ATC | N06AX16 |
| Molecular formula | C17H27NO2 |
| Molecular weight | 277.4 |
| InChIKey | PNVNVHUZROJLTJ-UHFFFAOYSA-N |
SMILES: CN(C)CC(C1=CC=C(C=C1)OC)C2(CCCCC2)O
IUPAC name: 1-[2-(dimethylamino)-1-(4-methoxyphenyl)ethyl]cyclohexan-1-ol
ChEBI definition: A tertiary amino compound that is N,N-dimethylethanamine substituted at position 1 by a 1-hydroxycyclohexyl and 4-methoxyphenyl group.
Pharmacological roles (ChEBI): antidepressant, serotonin uptake inhibitor, adrenergic uptake inhibitor, dopamine uptake inhibitor, analgesic.
Other ChEBI roles (chemical / environmental): environmental contaminant, xenobiotic.
Also known as: Alventa xl, Amphero xl, Bonilux xl, Depefex xl, Efectin, Efexor, Efexor xl, Foraven xl, Kanghong, Mentaven xl, NSC-758676, Politid xl
Parent form; salt/anhydrous children: CHEMBL1201066, CHEMBL3133301, CHEMBL5095051
Patent coverage: 9,794 distinct patent families (36,275 SureChEMBL compound mentions), from 1 matched compound structure(s). Mentions count patents naming the compound (not distinct inventions), so promiscuous / reference molecules inflate the mention figure — families are the dedup metric.
Targets
Targets
Primary targets (GtoPdb curated mechanism): the Cancer dependency column is the DepMap CRISPR fitness signal (% of screened cell lines dependent on the target).
| Gene | Target | Action | pAffinity | Cancer dependency | UniProt |
|---|---|---|---|---|---|
| SLC6A2 | NET | Inhibition | 6.27 | 0.4% | P23975 |
| SLC6A4 | SERT | Inhibition | 7.57 | 0.7% | P31645 |
Broader ChEMBL bioactivity targets: 11 (assay-derived). Sample: Prelamin-A/C, Cannabinoid receptor 1, Sodium-dependent noradrenaline transporter, 5-hydroxytryptamine receptor 2A, Sodium-dependent serotonin transporter, Histamine H1 receptor, Sodium-dependent dopamine transporter, Histamine H3 receptor, Sodium-dependent serotonin transporter, Alpha-1A adrenergic receptor.
Bioactivity
ChEMBL activities: 53 potent at pChembl ≥ 5 of 56 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):
| Target | pChembl | Type | Value | Unit | Activity ID |
|---|---|---|---|---|---|
| LMNA | 8.7 | Potency | 2 | nM | CHEMBL_ACT_3664398 |
| SLC6A4 | 8.42 | Ki | 3.81 | nM | CHEMBL_ACT_7792839 |
| SLC6A4 | 8.14 | IC50 | 7.18 | nM | CHEMBL_ACT_7792838 |
| SLC6A4 | 8.05 | Kd | 8.9 | nM | CHEMBL_ACT_158294 |
| SLC6A4 | 7.96 | Ki | 11 | nM | CHEMBL_ACT_13325671 |
| SLC6A4 | 7.7 | IC50 | 20 | nM | CHEMBL_ACT_12167028 |
| SLC6A4 | 7.7 | IC50 | 20 | nM | CHEMBL_ACT_18652503 |
| P31652 | 7.6 | Ki | 25 | nM | CHEMBL_ACT_13325639 |
| SLC6A4 | 7.6 | AC50 | 25 | nM | CHEMBL_ACT_25150775 |
| SLC6A4 | 7.57 | IC50 | 27 | nM | CHEMBL_ACT_3285114 |
| SLC6A4 | 7.51 | IC50 | 31 | nM | CHEMBL_ACT_2454414 |
| SLC6A4 | 7.46 | IC50 | 35 | nM | CHEMBL_ACT_3414446 |
| SLC6A4 | 7.44 | IC50 | 36.1 | nM | CHEMBL_ACT_15002110 |
| P31652 | 7.43 | Ki | 37 | nM | CHEMBL_ACT_158298 |
| SLC6A4 | 7.41 | Ki | 39 | nM | CHEMBL_ACT_18566467 |
| P31652 | 7.28 | Ki | 52 | nM | CHEMBL_ACT_462313 |
| P43140 | 7.05 | IC50 | 90 | nM | CHEMBL_ACT_726781 |
| P31652 | 7 | IC50 | 100 | nM | CHEMBL_ACT_728125 |
| P43140 | 6.96 | IC50 | 109 | nM | CHEMBL_ACT_728123 |
| SLC6A4 | 6.95 | Ki | 113 | nM | CHEMBL_ACT_13336316 |
| P43140 | 6.85 | IC50 | 140 | nM | CHEMBL_ACT_745723 |
| SLC6A2 | 6.83 | IC50 | 149 | nM | CHEMBL_ACT_12167023 |
| SLC6A2 | 6.83 | IC50 | 149 | nM | CHEMBL_ACT_18652510 |
| P31652 | 6.72 | IC50 | 190 | nM | CHEMBL_ACT_745725 |
| SLC6A2 | 6.68 | Ki | 210 | nM | CHEMBL_ACT_18566472 |
| P31652 | 6.68 | IC50 | 210 | nM | CHEMBL_ACT_2454416 |
| P31652 | 6.68 | IC50 | 210 | nM | CHEMBL_ACT_726783 |
| SLC6A4 | 6.49 | IC50 | 323.6 | nM | CHEMBL_ACT_13336317 |
| P31652 | 6.46 | IC50 | 350 | nM | CHEMBL_ACT_3093400 |
| P23977 | 6.44 | Ki | 360 | nM | CHEMBL_ACT_158300 |
Target pathways
Aggregated over 2 target gene(s): SLC6A2, SLC6A4.
Top Reactome pathways
12 total, by targets touching each:
| Pathway | Targets | Genes |
|---|---|---|
| SLC-mediated transport of neurotransmitters | 2 | SLC6A2, SLC6A4 |
| Neurotransmitter clearance | 1 | SLC6A4 |
| Transmission across Chemical Synapses | 1 | SLC6A4 |
| Neuronal System | 1 | SLC6A4 |
| Disease | 1 | SLC6A2 |
| Serotonin clearance from the synaptic cleft | 1 | SLC6A4 |
| Transport of small molecules | 1 | SLC6A2 |
| R-HSA-425366 | 1 | SLC6A2 |
| SLC-mediated transmembrane transport | 1 | SLC6A2 |
| SLC transporter disorders | 1 | SLC6A2 |
| Defective SLC6A2 causes orthostatic intolerance (OI) | 1 | SLC6A2 |
| Disorders of transmembrane transporters | 1 | SLC6A2 |
Dominant GO biological processes
| GO term | Targets |
|---|---|
| neurotransmitter transport | 2 |
| amino acid transport | 2 |
| response to xenobiotic stimulus | 2 |
| obsolete monoamine transport | 2 |
| sodium ion transmembrane transport | 2 |
| transmembrane transport | 2 |
| neurotransmitter reuptake | 2 |
| chemical synaptic transmission | 1 |
| obsolete norepinephrine transport | 1 |
| response to pain | 1 |
| dopamine uptake involved in synaptic transmission | 1 |
| norepinephrine uptake | 1 |
| neuron cellular homeostasis | 1 |
| catecholamine uptake | 1 |
| chloride transmembrane transport | 1 |
Indications & clinical
Indications
2 indications (2 at ChEMBL trial phase 4). Phase below is the highest clinical-trial phase recorded for this drug against each disease — not the molecule’s overall approval status (that is in the Summary).
| Indication | Trial phase | MONDO | EFO |
|---|---|---|---|
| depressive disorder | 4 | MONDO:0002050 | MONDO:0002050 |
1 further indication record had no mapped disease name (EFO/MeSH-only) or were duplicates, and are omitted.
Clinical trials
Total trials: 114.
Phase distribution
| Phase | Trials |
|---|---|
| PHASE4 | 40 |
| Not specified | 23 |
| PHASE3 | 20 |
| PHASE2 | 13 |
| PHASE1 | 9 |
| PHASE2/PHASE3 | 5 |
| PHASE1/PHASE2 | 4 |
Top trials by phase / activity
| NCT | Phase | Status | Title |
|---|---|---|---|
| NCT06803485 | PHASE4 | RECRUITING | Effect of Venlafaxine Versus Dosulepin in Pain Predominant Somatic Symptom Disorder |
| NCT00045916 | PHASE4 | COMPLETED | Optimizing Electroconvulsive Therapy for Depression |
| NCT00150839 | PHASE4 | COMPLETED | Hippocampal Volume in Young Patients With Major Depression Before and After Combined Antidepressive Therapy |
| NCT00177567 | PHASE4 | COMPLETED | Treatment of Geriatric Bipolar Mood Disorders: A Pilot Study |
| NCT00177671 | PHASE4 | COMPLETED | Antidepressant Medication Plus Donepezil for Treating Late-life Depression |
| NCT00188643 | PHASE4 | COMPLETED | Venlafaxine Versus Lamotrigine in the Treatment of Bipolar I/II Depression |
| NCT00205491 | PHASE4 | COMPLETED | Pharmacological Intervention in Depression After Traumatic Brain Injury |
| NCT00211809 | PHASE4 | TERMINATED | CBT as an Adjunct to SRIs in the Treatment of BDD |
| NCT00253266 | PHASE4 | COMPLETED | Venlafaxine Augmentation in Treatment Resistant Depression |
| NCT00282828 | PHASE4 | COMPLETED | Improving Treatment Outcomes in Pharmacotherapy of Generalized Social Anxiety Disorder |
| NCT00316160 | PHASE4 | COMPLETED | Sexual Functioning Study With Antidepressants |
| NCT00602537 | PHASE4 | COMPLETED | Antidepressant Therapy in Treating Bipolar Type II Major Depression |
| NCT00611676 | PHASE4 | COMPLETED | A Single-Blind Placebo Run-In Study of Venlafaxine for Activity-Limiting Osteoarthritis Pain |
| NCT00627887 | PHASE4 | COMPLETED | Randomised Controlled Trial of Electroconvulsive Therapy (ECT) in Relapse Prevention of Depression |
| NCT00634283 | PHASE4 | COMPLETED | Study of the Effects of an Antidepressant Medication and Placebo on the Brain Functioning of Normal Subjects |
| NCT00641927 | PHASE4 | COMPLETED | Antidepressant Therapy for Bipolar II Major Depression |
| NCT00759122 | PHASE4 | COMPLETED | Electroencephalography (EEG) Biomarkers of Response in Depression |
| NCT00759317 | PHASE4 | COMPLETED | Physiologic Monitoring of Antidepressant Treatment Response |
| NCT00792168 | PHASE4 | COMPLETED | Physiologic Monitoring of Antidepressant Response |
| NCT00974155 | PHASE4 | COMPLETED | The Early Medication Change (EMC) Trial |
| NCT01028508 | PHASE4 | COMPLETED | Prolonging Remission in Depressed Elderly (PRIDE) |
| NCT01124188 | PHASE4 | COMPLETED | ADAPT: Addressing Depression and Pain Together |
| NCT01204086 | PHASE4 | UNKNOWN | Pharmacogenomics Studies of Antidepressants |
| NCT01436643 | PHASE4 | TERMINATED | Combination of Antidepressants and Fingolimod Relapsing-remitting Multiple Sclerosis (RRMS) Patients With Depression |
| NCT01443520 | PHASE4 | COMPLETED | Effect of Duloxetine and Venlafaxine on the Pharmacokinetics and Pharmacodynamics of Oral Tramadol: A Three-phase Randomized Balanced Cross-over Study in Healthy Volunteers |
| NCT01569685 | PHASE4 | COMPLETED | The Treatment of Traumatised Refugees With Sertraline Versus Venlafaxine in Combination With Psychotherapy |
| NCT01658228 | PHASE4 | COMPLETED | Combination Treatment Study for Memory Impairment and Depression |
| NCT01764867 | PHASE4 | UNKNOWN | Algorithm Guided Treatment Strategies for Major Depressive Disorder |
| NCT01824433 | PHASE4 | COMPLETED | Comparison of Venlafaxine and Fluoxetine in the Treatment of Postmenopausal Women With Major Depression |
| NCT02237937 | PHASE4 | UNKNOWN | Optimizing Antidepressant Treatment by Genotype-dependent Adjustment of Medication According to the ABCB1 Gene |
| NCT02346682 | PHASE4 | UNKNOWN | Neurochemical, Metabonomics and Neuroimaging Characterization of TCM Diagnostic Subtypes of Major Depression Disorder |
| NCT02350985 | PHASE4 | COMPLETED | Comparison of Propranolol and Venlafaxine in Treatment of Vestibular Migraine |
| NCT02714400 | PHASE4 | COMPLETED | The Impact of Venlafaxine on Apnea Hypopnea Index in Obstructive Sleep Apnea |
| NCT04207385 | PHASE4 | UNKNOWN | Accurate Clinical Study of Medication in Patients With Depression Via Pharmacogenomics (PGx) and Therapeutic Drug Monitoring (TDM) of Venlafaxine |
| NCT04977271 | PHASE4 | WITHDRAWN | Mood Disorders in Head and Neck Cancer Patients |
| NCT05023278 | PHASE4 | COMPLETED | The Use of Venlafaxine in Reducing Pain in Primary Total Knee Replacement |
| NCT05569031 | PHASE4 | COMPLETED | Treatment of Withdrawal Symptoms and Prevention of Relapse in Patients With Tramadol Abuse |
| NCT05875610 | PHASE4 | UNKNOWN | Preventive Approach Using Venlafaxine |
| NCT06131268 | PHASE4 | UNKNOWN | The Role of Negr1 In Modulating Neuroplasticity in Major Depression (RONIN) |
| NCT06295562 | PHASE4 | COMPLETED | Pharmacological Treatment Targeting Endotypic Traits of Obstructive Sleep Apnea |
Clinical evidence (CIViC)
No CIViC predictive evidence (expected for non-precision-medicine drugs).
Pharmacology
Pharmacogenomics
PharmGKB dosing guidelines (4) — CPIC / DPWG genotype-guided dosing for this drug (drug × pharmacogene):
| Guideline | Source | Gene(s) | Dosing | Recommendation |
|---|---|---|---|---|
| Annotation of DPWG Guideline for venlafaxine and CYP2D6 | DPWG | CYP2D6 | yes | yes |
| Annotation of CPIC Guideline for venlafaxine and CYP2D6 | CPIC | CYP2D6 | yes | |
| Annotation of CPIC Guideline for desvenlafaxine, duloxetine, fluoxetin | CPIC | HTR2A | ||
| Annotation of CPIC Guideline for citalopram, desvenlafaxine, duloxetin | CPIC | SLC6A4 |
PharmGKB also curates 37 clinical and 141 variant annotation(s) for this drug (gene-keyed; see PharmGKB).
Related molecules
Related molecules
Molecules sharing ≥1 of this drug’s curated primary targets, merged from two biobtree sources and ranked by shared-target count, then clinical phase: ChEMBL clinical-stage candidates (development phase ≥2) and PubChem drug-class bioactivity (approved / known drugs acting on the target). Deduplicated by drug name; the drug’s own salt forms are excluded. Note: for a drug with few primary targets a shared-target match can reflect off-target / promiscuous binding rather than the same therapeutic mechanism — the phase ordering surfaces bona-fide therapeutics first.
592 molecules share ≥1 primary target. Top 60 by shared-target count:
| Molecule | Source | Status | Shared targets |
|---|---|---|---|
| AMITRIPTYLINE | ChEMBL + PubChem | Phase 4 (approved) | SLC6A2, SLC6A4 |
| CRIZOTINIB | ChEMBL + PubChem | Phase 4 (approved) | SLC6A2, SLC6A4 |
| GENTIAN VIOLET | ChEMBL + PubChem | Phase 4 (approved) | SLC6A2, SLC6A4 |
| Olodaterol | ChEMBL + PubChem | Phase 4 (approved) | SLC6A2, SLC6A4 |
| PIMAVANSERIN | ChEMBL + PubChem | Phase 4 (approved) | SLC6A2, SLC6A4 |
| REGORAFENIB | ChEMBL + PubChem | Phase 4 (approved) | SLC6A2, SLC6A4 |
| Tadalafil | ChEMBL + PubChem | Phase 4 (approved) | SLC6A2, SLC6A4 |
| TAFENOQUINE | ChEMBL + PubChem | Phase 4 (approved) | SLC6A2, SLC6A4 |
| UMECLIDINIUM | ChEMBL + PubChem | Phase 4 (approved) | SLC6A2, SLC6A4 |
| VORAPAXAR | ChEMBL + PubChem | Phase 4 (approved) | SLC6A2, SLC6A4 |
| ACETOPHENAZINE | ChEMBL | Phase 4 (approved) | SLC6A2, SLC6A4 |
| ALECTINIB | ChEMBL | Phase 4 (approved) | SLC6A2, SLC6A4 |
| AMBENONIUM | ChEMBL | Phase 4 (approved) | SLC6A2, SLC6A4 |
| AMIODARONE | ChEMBL | Phase 4 (approved) | SLC6A2, SLC6A4 |
| AMOXAPINE | ChEMBL | Phase 4 (approved) | SLC6A2, SLC6A4 |
| ARIPIPRAZOLE | ChEMBL | Phase 4 (approved) | SLC6A2, SLC6A4 |
| ASENAPINE | ChEMBL | Phase 4 (approved) | SLC6A2, SLC6A4 |
| ASTEMIZOLE | ChEMBL | Phase 4 (approved) | SLC6A2, SLC6A4 |
| ATOMOXETINE | ChEMBL | Phase 4 (approved) | SLC6A2, SLC6A4 |
| ATRACURIUM | ChEMBL | Phase 4 (approved) | SLC6A2, SLC6A4 |
| AZELASTINE | ChEMBL | Phase 4 (approved) | SLC6A2, SLC6A4 |
| BAZEDOXIFENE | ChEMBL | Phase 4 (approved) | SLC6A2, SLC6A4 |
| BENFLUOREX | ChEMBL | Phase 4 (approved) | SLC6A2, SLC6A4 |
| BENZPHETAMINE | ChEMBL | Phase 4 (approved) | SLC6A2, SLC6A4 |
| BENZTROPINE | ChEMBL | Phase 4 (approved) | SLC6A2, SLC6A4 |
| BENZYDAMINE | ChEMBL | Phase 4 (approved) | SLC6A2, SLC6A4 |
| BEPRIDIL | ChEMBL | Phase 4 (approved) | SLC6A2, SLC6A4 |
| BOSUTINIB | ChEMBL | Phase 4 (approved) | SLC6A2, SLC6A4 |
| BREXPIPRAZOLE | ChEMBL | Phase 4 (approved) | SLC6A2, SLC6A4 |
| BROMHEXINE | ChEMBL | Phase 4 (approved) | SLC6A2, SLC6A4 |
| BROMODIPHENHYDRAMINE | ChEMBL | Phase 4 (approved) | SLC6A2, SLC6A4 |
| BROMPERIDOL | ChEMBL | Phase 4 (approved) | SLC6A2, SLC6A4 |
| BROMPHENIRAMINE | ChEMBL | Phase 4 (approved) | SLC6A2, SLC6A4 |
| BUPROPION | ChEMBL | Phase 4 (approved) | SLC6A2, SLC6A4 |
| BUTENAFINE | ChEMBL | Phase 4 (approved) | SLC6A2, SLC6A4 |
| CABERGOLINE | ChEMBL | Phase 4 (approved) | SLC6A2, SLC6A4 |
| CALCIPOTRIENE | ChEMBL | Phase 4 (approved) | SLC6A2, SLC6A4 |
| CALCITRIOL | ChEMBL | Phase 4 (approved) | SLC6A2, SLC6A4 |
| CARBINOXAMINE | ChEMBL | Phase 4 (approved) | SLC6A2, SLC6A4 |
| CARVEDILOL | ChEMBL | Phase 4 (approved) | SLC6A2, SLC6A4 |
| CELECOXIB | ChEMBL | Phase 4 (approved) | SLC6A2, SLC6A4 |
| CETIRIZINE | ChEMBL | Phase 4 (approved) | SLC6A2, SLC6A4 |
| CHLORHEXIDINE | ChEMBL | Phase 4 (approved) | SLC6A2, SLC6A4 |
| CHLORPHENIRAMINE | ChEMBL | Phase 4 (approved) | SLC6A2, SLC6A4 |
| CHLORPHENTERMINE | ChEMBL | Phase 4 (approved) | SLC6A2, SLC6A4 |
| CHLORPROMAZINE | ChEMBL | Phase 4 (approved) | SLC6A2, SLC6A4 |
| CHLORPROTHIXENE | ChEMBL | Phase 4 (approved) | SLC6A2, SLC6A4 |
| CINACALCET | ChEMBL | Phase 4 (approved) | SLC6A2, SLC6A4 |
| CINNARIZINE | ChEMBL | Phase 4 (approved) | SLC6A2, SLC6A4 |
| CITALOPRAM | ChEMBL | Phase 4 (approved) | SLC6A2, SLC6A4 |
| CLEMASTINE | ChEMBL | Phase 4 (approved) | SLC6A2, SLC6A4 |
| CLOMIPHENE | ChEMBL | Phase 4 (approved) | SLC6A2, SLC6A4 |
| CLOMIPRAMINE | ChEMBL | Phase 4 (approved) | SLC6A2, SLC6A4 |
| CLOTRIMAZOLE | ChEMBL | Phase 4 (approved) | SLC6A2, SLC6A4 |
| CLOZAPINE | ChEMBL | Phase 4 (approved) | SLC6A2, SLC6A4 |
| COBIMETINIB | ChEMBL | Phase 4 (approved) | SLC6A2, SLC6A4 |
| COCAINE | ChEMBL | Phase 4 (approved) | SLC6A2, SLC6A4 |
| CYCLOBENZAPRINE | ChEMBL | Phase 4 (approved) | SLC6A2, SLC6A4 |
| CYPROHEPTADINE | ChEMBL | Phase 4 (approved) | SLC6A2, SLC6A4 |
| DANAZOL | ChEMBL | Phase 4 (approved) | SLC6A2, SLC6A4 |
Related Atlas pages
- Genes: SLC6A2, SLC6A4
- Diseases: depressive disorder
- Drugs: Amitriptyline, Crizotinib, Olodaterol, Pimavanserin, Regorafenib, Tadalafil, Tafenoquine, Umeclidinium, Vorapaxar, Acetophenazine, Alectinib, Ambenonium, Amiodarone, Amoxapine, Aripiprazole, Asenapine, Astemizole, Atomoxetine, Atracurium, Azelastine, Bazedoxifene, Benfluorex, Benzphetamine, Benztropine, Benzydamine, Bepridil, Bosutinib, Brexpiprazole, Bromhexine, Bromodiphenhydramine, Bromperidol, Brompheniramine, Bupropion, Butenafine, Cabergoline, Calcipotriene, Calcitriol, Carbinoxamine, Carvedilol, Celecoxib, Cetirizine, Chlorhexidine, Chlorpheniramine, Chlorphentermine, Chlorpromazine, Chlorprothixene, Cinacalcet, Cinnarizine, Citalopram, Clemastine, Clomiphene, Clomipramine, Clotrimazole, Clozapine, Cobimetinib, Cocaine, Cyclobenzaprine, Cyproheptadine, Danazol