Identification

Name
Duloxetine
Accession Number
DB00476  (APRD00060)
Type
Small Molecule
Groups
Approved
Description

Duloxetine (brand names Cymbalta, Yentreve, and in parts of Europe, Xeristar or Ariclaim) is a drug which primarily targets major depressive disorder (MDD), generalized anxiety disorder (GAD), pain related to diabetic peripheral neuropathy and in some countries stress urinary incontinence (SUI). It is manufactured and marketed by Eli Lilly and Company.

Duloxetine has not yet been FDA approved for stress urinary incontinence or for fibromyalgia.

Duloxetine is a selective SNRI (selective serotonin-norepinephrine reuptake inhibitor). Duloxetine is a systemic drug therapy which affects the body as a whole. Known also under the code name LY248686, it is a potent dual reuptake inhibitor of serotonin (5-hydroxytryptamine, 5-HT) and norepinephrine (NE), possessing comparable affinities in binding to NE- and 5-HT transporter sites. It is a less potent inhibitor of dopamine reuptake.

Structure
Thumb
Synonyms
  • (3S)-N-methyl-3-(1-naphthyloxy)-3-(2-thienyl)propan-1-amine
  • (S)-duloxetine
  • Duloxetina
External IDs
LY 248686 / LY-248686 / LY248686
Product Ingredients
IngredientUNIICASInChI Key
Duloxetine hydrochloride9044SC542W136434-34-9BFFSMCNJSOPUAY-LMOVPXPDSA-N
Product Images
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Act DuloxetineCapsule, delayed release30 mgOralActavis Pharma CompanyNot applicableNot applicableCanada
Act DuloxetineCapsule, delayed release60 mgOralActavis Pharma CompanyNot applicableNot applicableCanada
CymbaltaCapsule, delayed release60 mg/1OralSt. Marys Medical Park Pharmacy2010-12-312015-06-30Us
CymbaltaCapsule, delayed release30 mgOralEli Lilly Nederland B.V.2004-12-17Not applicableEu
CymbaltaCapsule, delayed release30 mg/1OralPhysicians Total Care, Inc.2008-11-21Not applicableUs54868 531520180907 15195 ayw0i5
CymbaltaCapsule, delayed release30 mg/1OralLake Erie Medical &Surgical Supply Dba Quality Care Products Llc2011-07-14Not applicableUs
CymbaltaCapsule, delayed release30 mg/1OralA-S Medication Solutions2004-08-24Not applicableUs54569 594120180907 15195 k45cot
CymbaltaCapsule, delayed release60 mg/1Oralbryant ranch prepack2010-01-152018-05-29Us63629 334020180907 15195 1wfqw3h
CymbaltaCapsule, delayed release30 mg/1OralEli Lilly & Co. Ltd.2004-08-24Not applicableUs0002 324020180810 16125 1eqxt3y
CymbaltaCapsule, delayed release60 mgOralEli Lilly Nederland B.V.2004-12-17Not applicableEu
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Apo-duloxetineCapsule, delayed release30 mgOralApotex Corporation2016-05-03Not applicableCanada
Apo-duloxetineCapsule, delayed release60 mgOralApotex Corporation2016-05-03Not applicableCanada
Auro-duloxetineCapsule, delayed release30 mgOralAuro Pharma Inc2016-05-02Not applicableCanada
Auro-duloxetineCapsule, delayed release60 mgOralAuro Pharma Inc2016-05-02Not applicableCanada
Dom-duloxetineCapsule, delayed release30 mgOralDominion PharmacalNot applicableNot applicableCanada
Dom-duloxetineCapsule, delayed release60 mgOralDominion PharmacalNot applicableNot applicableCanada
DuloxetineCapsule, delayed release30 mg/1OralRemedy Repack2017-05-08Not applicableUs
DuloxetineCapsule, delayed release60 mg/1Oralbryant ranch prepack2017-03-16Not applicableUs
DuloxetineCapsule, delayed release60 mg/1OralCadila Pharnmaceuticals2014-02-15Not applicableUs
DuloxetineCapsule, delayed release30 mg/1OralCamber Pharmaceuticals2016-08-11Not applicableUs
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
DermacinRx DPN PakDuloxetine hydrochloride (60 mg/1) + Lidocaine hydrochloride anhydrous (50 mg/1mL) + Menthol (30 mg/1mL)KitPure Tek Corporation2016-05-262017-08-17Us
Unapproved/Other Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
AriclaimDuloxetine (30 mg)Capsule, delayed releaseOralEli Lilly Nederland B.V.2004-08-112018-08-07Eu
AriclaimDuloxetine (30 mg)Capsule, delayed releaseOralEli Lilly Nederland B.V.2004-08-112018-08-07Eu
AriclaimDuloxetine (60 mg)Capsule, delayed releaseOralEli Lilly Nederland B.V.2004-08-112018-08-07Eu
AriclaimDuloxetine (30 mg)Capsule, delayed releaseOralEli Lilly Nederland B.V.2004-08-112018-08-07Eu
AriclaimDuloxetine (60 mg)Capsule, delayed releaseOralEli Lilly Nederland B.V.2004-08-112018-08-07Eu
International/Other Brands
Ariclaim / Dulane / Duzela / Xeristar / Yentreve
Categories
UNII
O5TNM5N07U
CAS number
116539-59-4
Weight
Average: 297.415
Monoisotopic: 297.118734925
Chemical Formula
C18H19NOS
InChI Key
ZEUITGRIYCTCEM-KRWDZBQOSA-N
InChI
InChI=1S/C18H19NOS/c1-19-12-11-17(18-10-5-13-21-18)20-16-9-4-7-14-6-2-3-8-15(14)16/h2-10,13,17,19H,11-12H2,1H3/t17-/m0/s1
IUPAC Name
methyl[(3S)-3-(naphthalen-1-yloxy)-3-(thiophen-2-yl)propyl]amine
SMILES
CNCC[C@H](OC1=CC=CC2=CC=CC=C12)C1=CC=CS1

Pharmacology

Indication

For the acute and maintenance treatment of major depressive disorder (MDD), as well as acute management of generalized anxiety disorder. Also used for the management of neuropathic pain associated with diabetic peripheral neuropathy, and fibromyalgia. Has been used in the management of moderate to severe stress urinary incontinence (SUI) in women.

Associated Conditions
Pharmacodynamics

Duloxetine is in a class of medications called selective serotonin and norepinephrine reuptake inhibitors (SSNRIs) and primarily targets major depressive disorders (MDD) and stress urinary incontinence (SUI). Duloxetine is also used to treat pain and tingling caused by diabetic neuropathy (damage to nerves that can develop in people who have diabetes). Known also as LY248686, it is a potent dual inhibitor of serotonin (5-hydroxytryptamine, 5-HT) and norepinephrine (NE) reuptake, possessing comparable affinities in binding to NE and 5-HT transport sites. Interestingly, its behavior contrasts to most other dual-reuptake inhibitors. Furthermore, duloxentine lacks affinity for monoamine receptors within the central nervous system.

Mechanism of action

Duloxetine is a potent inhibitor of neuronal serotonin and norepinephrine reuptake and a less potent inhibitor of dopamine reuptake. Duloxetine has no significant affinity for dopaminergic, adrenergic, cholinergic, histaminergic, opioid, glutamate, and GABA receptors. The antidepressant and pain inhibitory actions of duloxetine are believed to be related to its potentiation of serotonergic and noradrenergic activity in the CNS. The mechanism of action of duloxetine in SUI has not been determined, but is thought to be associated with the potentiation of serotonin and norepinephrine activity in the spinal cord, which increases urethral closure forces and thereby reduces involuntary urine loss.

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

Orally administered duloxetine hydrochloride is well absorbed.

Volume of distribution
  • 1640 L
Protein binding

Protein binding is greater than 90%.

Metabolism

The major biotransformation pathways for duloxetine involve oxidation of the naphthyl ring followed by conjugation and further oxidation. Both CYP2D6 and CYP1A2 catalyze the oxidation of the naphthyl ring in vitro. Metabolites found in plasma include 4-hydroxy duloxetine glucuronide and 5-hydroxy, 6-methoxy duloxetine sulfate. The major circulating metabolites have not been shown to contribute significantly to the pharmacologic activity of duloxetine.

Route of elimination

Many additional metabolites have been identified in urine, some representing only minor pathways of elimination. Most (about 70%) of the duloxetine dose appears in the urine as metabolites of duloxetine; about 20% is excreted in the feces.

Half life

12 hours (range 8-17 hours)

Clearance
Not Available
Toxicity

Oral, rat LD50: 491 mg/kg for males and 279 mg/kg for females. Symptoms of overdose include tremors, convulsions, reduced activity, slow pupillary response, intermittent tremors, and rigidity.

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Interacting Gene/EnzymeAllele nameGenotype(s)Defining Change(s)Type(s)DescriptionDetails
Cytochrome P450 2D6CYP2D6*3Not AvailableC alleleEffect InferredPoor drug metabolizer.Details
Cytochrome P450 2D6CYP2D6*4Not AvailableC alleleEffect InferredPoor drug metabolizer.Details
Cytochrome P450 2D6CYP2D6*5Not AvailableWhole-gene deletionEffect InferredPoor drug metabolizer.Details
Cytochrome P450 2D6CYP2D6*6Not Available1707delTEffect InferredPoor drug metabolizer.Details
Cytochrome P450 2D6CYP2D6*7Not Available2935A>CEffect InferredPoor drug metabolizer.Details
Cytochrome P450 2D6CYP2D6*8Not Available1758G>TEffect InferredPoor drug metabolizer.Details
Cytochrome P450 2D6CYP2D6*11Not Available883G>CEffect InferredPoor drug metabolizer.Details
Cytochrome P450 2D6CYP2D6*12Not Available124G>AEffect InferredPoor drug metabolizer.Details
Cytochrome P450 2D6CYP2D6*13Not AvailableCYP2D7/2D6 hybrid gene structureEffect InferredPoor drug metabolizer.Details
Cytochrome P450 2D6CYP2D6*14ANot Available1758G>AEffect InferredPoor drug metabolizer.Details
Cytochrome P450 2D6CYP2D6*15Not Available137insT, 137_138insTEffect InferredPoor drug metabolizer.Details
Cytochrome P450 2D6CYP2D6*19Not Available2539_2542delAACTEffect InferredPoor drug metabolizer.Details
Cytochrome P450 2D6CYP2D6*20Not Available1973_1974insGEffect InferredPoor drug metabolizer.Details
Cytochrome P450 2D6CYP2D6*21Not Available2573insCEffect InferredPoor drug metabolizer.Details
Cytochrome P450 2D6CYP2D6*31Not Available-1770G>A / -1584C>G  … show all Effect InferredPoor drug metabolizer.Details
Cytochrome P450 2D6CYP2D6*36Not Available100C>T / -1426C>T  … show all Effect InferredPoor drug metabolizer.Details
Cytochrome P450 2D6CYP2D6*38Not Available2587_2590delGACTEffect InferredPoor drug metabolizer.Details
Cytochrome P450 2D6CYP2D6*40Not Available1863_1864ins(TTT CGC CCC)2Effect InferredPoor drug metabolizer.Details
Cytochrome P450 2D6CYP2D6*42Not Available3259_3260insGTEffect InferredPoor drug metabolizer.Details
Cytochrome P450 2D6CYP2D6*44Not Available2950G>CEffect InferredPoor drug metabolizer.Details
Cytochrome P450 2D6CYP2D6*47Not Available100C>T / -1426C>T  … show all Effect InferredPoor drug metabolizer.Details
Cytochrome P450 2D6CYP2D6*51Not Available-1584C>G / -1235A>G  … show all Effect InferredPoor drug metabolizer.Details
Cytochrome P450 2D6CYP2D6*56Not Available3201C>TEffect InferredPoor drug metabolizer.Details
Cytochrome P450 2D6CYP2D6*57Not Available100C>T / 310G>T  … show all Effect InferredPoor drug metabolizer.Details
Cytochrome P450 2D6CYP2D6*62Not Available4044C>TEffect InferredPoor drug metabolizer.Details
Cytochrome P450 2D6CYP2D6*68ANot Available-1426C>T / -1235A>G  … show all Effect InferredPoor drug metabolizer.Details
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.Details
Cytochrome P450 2D6CYP2D6*69Not Available2988G>A / -1426C>T  … show all Effect InferredPoor drug metabolizer.Details
Cytochrome P450 2D6CYP2D6*92Not Available1995delCEffect InferredPoor drug metabolizer.Details
Cytochrome P450 2D6CYP2D6*100Not Available-1426C>T / -1235A>G  … show all Effect InferredPoor drug metabolizer.Details
Cytochrome P450 2D6CYP2D6*101Not Available-1426C>T / -1235A>G  … show all Effect InferredPoor drug metabolizer.Details
Cytochrome P450 1A2CYP1A2*6Not Available5090C>TEffect InferredPoor drug metabolizer.Details

Interactions

Drug Interactions
DrugInteraction
(R)-warfarinDuloxetine may increase the antiplatelet activities of (R)-warfarin.
(S)-WarfarinDuloxetine may increase the antiplatelet activities of (S)-Warfarin.
2,4-thiazolidinedioneThe risk or severity of hypoglycemia can be increased when Duloxetine is combined with 2,4-thiazolidinedione.
2,5-Dimethoxy-4-ethylamphetamineThe risk or severity of serotonin syndrome can be increased when Duloxetine is combined with 2,5-Dimethoxy-4-ethylamphetamine.
2,5-Dimethoxy-4-ethylthioamphetamineThe risk or severity of adverse effects can be increased when 2,5-Dimethoxy-4-ethylthioamphetamine is combined with Duloxetine.
3-isobutyl-1-methyl-7H-xanthineThe serum concentration of 3-isobutyl-1-methyl-7H-xanthine can be increased when it is combined with Duloxetine.
3,4-MethylenedioxyamphetamineThe risk or severity of adverse effects can be increased when 3,4-Methylenedioxyamphetamine is combined with Duloxetine.
3,5-diiodothyropropionic acidThe therapeutic efficacy of 3,5-diiodothyropropionic acid can be decreased when used in combination with Duloxetine.
4-Bromo-2,5-dimethoxyamphetamineThe risk or severity of adverse effects can be increased when 4-Bromo-2,5-dimethoxyamphetamine is combined with Duloxetine.
4-hydroxycoumarinThe metabolism of 4-hydroxycoumarin can be decreased when combined with Duloxetine.
Food Interactions
  • Food does not affect maximum levels reached, but delays it (from 6 to 10 hours) and total product exposure appears to be reduced by only 10%.
  • People taking this product who drink large amounts of alcohol are exposed to a higher risk of liver toxicity.
  • Take without regard to meals.

References

Synthesis Reference

Richard A. Berglund, "Intermediate useful for the asymmetric synthesis of duloxetine." U.S. Patent US5491243, issued June, 1991.

US5491243
General References
  1. Turcotte JE, Debonnel G, de Montigny C, Hebert C, Blier P: Assessment of the serotonin and norepinephrine reuptake blocking properties of duloxetine in healthy subjects. Neuropsychopharmacology. 2001 May;24(5):511-21. [PubMed:11282251]
  2. Anttila S, Leinonen E: Duloxetine Eli Lilly. Curr Opin Investig Drugs. 2002 Aug;3(8):1217-21. [PubMed:12211418]
  3. Karpa KD, Cavanaugh JE, Lakoski JM: Duloxetine pharmacology: profile of a dual monoamine modulator. CNS Drug Rev. 2002 Winter;8(4):361-76. [PubMed:12481192]
  4. van Groeningen CJ, Peters GJ, Pinedo HM: Lack of effectiveness of combined 5-fluorouracil and leucovorin in patients with 5-fluorouracil-resistant advanced colorectal cancer. Eur J Cancer Clin Oncol. 1989 Jan;25(1):45-9. [PubMed:2784100]
  5. Jost W, Marsalek P: Duloxetine: mechanism of action at the lower urinary tract and Onuf's nucleus. Clin Auton Res. 2004 Aug;14(4):220-7. [PubMed:15316838]
  6. Carter NJ, McCormack PL: Duloxetine: a review of its use in the treatment of generalized anxiety disorder. CNS Drugs. 2009;23(6):523-41. doi: 10.2165/00023210-200923060-00006. [PubMed:19480470]
External Links
Human Metabolome Database
HMDB0014619
KEGG Drug
D01179
PubChem Compound
60835
PubChem Substance
46507937
ChemSpider
54822
BindingDB
84745
ChEBI
36795
ChEMBL
CHEMBL1175
Therapeutic Targets Database
DAP000494
PharmGKB
PA10066
IUPHAR
202
Guide to Pharmacology
GtP Drug Page
HET
29E
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Duloxetine
ATC Codes
N06AX21 — Duloxetine
AHFS Codes
  • 28:16.04.16 — Selective Serotonin and Norepinephrine-reuptake Inhibitors
PDB Entries
4mm6 / 4mmd
FDA label
Download (104 KB)
MSDS
Download (76.3 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
0CompletedBasic SciencePosttraumatic Stress Disorders1
0CompletedBasic ScienceStrokes1
0RecruitingTreatmentMajor Depressive Disorder (MDD) / Unipolar Depression1
1CompletedNot AvailableDrug Drug Interaction (DDI)1
1CompletedNot AvailableHealthy Volunteers1
1CompletedBasic ScienceAmphetamine-Related Disorders / Moods Disorders / Substance-Related Disorders1
1CompletedBasic ScienceAnticoagulant Effect of Warfarin When Taken With Duloxetine1
1CompletedBasic ScienceCocaine Use Disorders1
1CompletedTreatmentHealthy Volunteers2
1CompletedTreatmentHealthy Volunteers / Hyperalgesia1
1CompletedTreatmentMajor Depressive Disorder (MDD)1
1RecruitingBasic ScienceAlcohol Use Disorder (AUD)1
1RecruitingOtherMajor Depressive Disorder (MDD)1
1, 2Active Not RecruitingTreatmentKnee Osteoarthritis (Knee OA)1
2Active Not RecruitingTreatmentMajor Depressive Disorder (MDD)1
2CompletedTreatmentAlcohol Dependence1
2CompletedTreatmentAttention Deficit Disorder With Hyperactivity1
2CompletedTreatmentDepression2
2CompletedTreatmentDiabetic Neuropathies / Diabetic Neuropathy, Painful / Diabetic Polyneuropathy / Neuralgia, Diabetic1
2CompletedTreatmentHuman Immunodeficiency Virus (HIV) Infections / Peripheral Neuropathy1
2CompletedTreatmentMajor Depressive Disorder (MDD)4
2CompletedTreatmentPain, Neuropathic / Peripheral Neuropathy1
2CompletedTreatmentUrinary Incontinence (UI)1
2CompletedTreatmentUrinary Stress Incontinence2
2RecruitingPreventionPain, Neuropathic1
2RecruitingTreatmentGulf War Illness1
2RecruitingTreatmentPain NOS1
2TerminatedTreatmentBack Pain Lower Back1
2TerminatedTreatmentDepression / Traumatic Brain Injury (TBI)1
2TerminatedTreatmentDiabetic Neuropathic Pain1
2TerminatedTreatmentMajor Depressive Disorder (MDD)2
2WithdrawnTreatmentParkinson's Disease (PD)1
2, 3CompletedPreventionPostoperative Myalgia1
2, 3CompletedTreatmentDiabetes Mellitus (DM) / Peripheral Neuropathy1
2, 3CompletedTreatmentDisseminated Sclerosis1
2, 3CompletedTreatmentFatigue Syndrome, Chronic1
3Active Not RecruitingTreatmentCancer, Breast / Musculoskeletal Complications / Pain NOS1
3CompletedBasic ScienceParkinson's Disease (PD)1
3CompletedBasic SciencePost-gastrointestinal bypass surgery1
3CompletedSupportive CareNeurologic toxicity / Pain NOS / Peripheral Neuropathy / Unspecified Adult Solid Tumor, Protocol Specific1
3CompletedTreatmentAnxiety Disorders5
3CompletedTreatmentAnxiety States, Neurotic / Neuroses, Anxiety1
3CompletedTreatmentBack Pain Lower Back Chronic3
3CompletedTreatmentBack Pain Without Radiation2
3CompletedTreatmentCognition / Depression1
3CompletedTreatmentDepression1
3CompletedTreatmentDepression / Depressive Disorders / Major Depressive Disorder (MDD)1
3CompletedTreatmentDepression / Depressive Disorders / Major Depressive Disorder (MDD) / Moods Disorders / Psychiatric Disorder NOS1
3CompletedTreatmentDepression / Pain NOS1
3CompletedTreatmentDepressive Disorder, Treatment-Resistant / Major depressive disorder, recurrent episode2
3CompletedTreatmentDepressive Disorders1
3CompletedTreatmentDiabetic Neuropathies3
3CompletedTreatmentDiabetic Neuropathy, Painful3
3CompletedTreatmentDisseminated Sclerosis1
3CompletedTreatmentFeeling Anxious1
3CompletedTreatmentFibromyalgia7
3CompletedTreatmentFibromyalgia / Infection, Human Immunodeficiency Virus I1
3CompletedTreatmentGeneralized Anxiety Disorder (GAD)2
3CompletedTreatmentKnee Osteoarthritis (Knee OA)2
3CompletedTreatmentMajor Depressive Disorder (MDD)18
3CompletedTreatmentMajor depressive disorder, recurrent episode3
3CompletedTreatmentOsteoarthritis (OA)1
3CompletedTreatmentOsteoarthritis Knee Pain4
3CompletedTreatmentSphincter of Oddi Dysfunction1
3CompletedTreatmentStress Urinary Incontinence (SUI)2
3CompletedTreatmentUrinary Incontinence Stress1
3CompletedTreatmentUrinary Incontinence,Stress6
3CompletedTreatmentUrinary Stress Incontinence2
3Not Yet RecruitingOtherMajor Depressive Disorder (MDD)1
3RecruitingTreatmentAcute Lymphoblastic Leukemia, Pediatric1
3RecruitingTreatmentDepressive Disorder, Treatment-Resistant1
3RecruitingTreatmentDepressive Disorders2
3RecruitingTreatmentFibromyalgia1
3RecruitingTreatmentMajor Depressive Disorder (MDD)1
3RecruitingTreatmentProstate Cancer / Urinary Incontinence (UI)1
3TerminatedPreventionDepression1
3TerminatedTreatmentAnxiety Disorders / Dementias / Depression / Psychosomatic Disorders / Schizophrenic Disorders1
3Unknown StatusTreatmentPosttraumatic Stress Disorders1
4Active Not RecruitingSupportive CareIntervertebral Disc Degeneration1
4CompletedBasic ScienceHealthy Participants / Major Depressive Disorder (MDD)1
4CompletedBasic ScienceHealthy Volunteers1
4CompletedBasic ScienceOsteoarthritis (OA)1
4CompletedOtherHealthy Controls / Major Depressive Disorder (MDD)1
4CompletedPreventionMigraines1
4CompletedSupportive CareDepression / Mild Cognitive Impairment (MCI)1
4CompletedTreatmentAgeing / Back Pain / Major Depressive Disorder (MDD)1
4CompletedTreatmentAtypical Depression1
4CompletedTreatmentBack Pain Lower Back Chronic1
4CompletedTreatmentBinge Eating / Depression1
4CompletedTreatmentChronic Primary Headache / Major Depressive Disorder (MDD)1
4CompletedTreatmentCryptogenic Sensory Polyneuropathy1
4CompletedTreatmentDementias / Depression1
4CompletedTreatmentDepression4
4CompletedTreatmentDepression / Dysthymic Disorder1
4CompletedTreatmentDepression / Menopause / Vasomotor Symptoms1
4CompletedTreatmentDepressive Disorder NOS / Dysthymic Disorder1
4CompletedTreatmentDepressive Disorders1
4CompletedTreatmentDiabetic Neuropathies1
4CompletedTreatmentDiabetic Neuropathy, Painful2
4CompletedTreatmentDiabetic Peripheral Neuropathic Pain (DPN)1
4CompletedTreatmentFibromyalgia1
4CompletedTreatmentFibromyalgia, Primary / Fibromyalgia, Secondary1
4CompletedTreatmentGeneralized Anxiety Disorder (GAD)1
4CompletedTreatmentGeneralized Anxiety Disorder (GAD) / Irritable Bowel Syndrome (IBS)1
4CompletedTreatmentIdiopathic Parkinson's Disease / Major Depressive Disorder (MDD)1
4CompletedTreatmentIrritable Bowel Syndrome (IBS)1
4CompletedTreatmentIrritable Bowel Syndrome (IBS) / Irritable Bowel Syndrome Symptoms / Major Depressive Disorder (MDD)1
4CompletedTreatmentMajor Depressive Disorder (MDD)17
4CompletedTreatmentMajor Depressive Disorder (MDD) / Pain NOS / Soft Tissue Discomfort Syndrome1
4CompletedTreatmentObsessive Compulsive Disorder (OCD)1
4CompletedTreatmentOsteoarthritis (OA) / Pain NOS1
4CompletedTreatmentOsteoarthritis (OA) / Pain, Chronic1
4CompletedTreatmentPanic Disorders1
4CompletedTreatmentPsychotic Disorder NOS1
4CompletedTreatmentStress Urinary Incontinence (SUI)1
4CompletedTreatmentTotal Knee Arthroplasty (TKA)1
4CompletedTreatmentUrinary Incontinence,Stress1
4Enrolling by InvitationTreatmentJoint Disease / Pain, Acute / Pain, Chronic1
4Not Yet RecruitingNot AvailablePain, Neuropathic1
4Not Yet RecruitingOtherHealthy Volunteers1
4Not Yet RecruitingTreatmentDiagnosis and Treatment of Depression1
4RecruitingNot AvailableDepressive Disorders / Lactation1
4RecruitingBasic ScienceMajor Depressive Disorder (MDD)1
4RecruitingHealth Services ResearchPain, Chronic1
4RecruitingOtherBack Pain Lower Back Chronic / Neck Pain Chronic1
4RecruitingOtherDepression / Male Infertility1
4RecruitingTreatmentDepression / Hearing loss or impairment1
4RecruitingTreatmentDepressive Disorder, NOS / Dysthymic Disorder / Major Depressive Disorder (MDD)1
4RecruitingTreatmentPost-thoracotomy Pain1
4SuspendedTreatmentDepression1
4TerminatedTreatmentBack Pain Lower Back Chronic / Diabetic Neuropathic Pain1
4TerminatedTreatmentDepression1
4TerminatedTreatmentFibromyalgia1
4TerminatedTreatmentPelvis Pain Chronic1
4Unknown StatusBasic ScienceMajor Depressive Disorder (MDD)1
4Unknown StatusDiagnosticSchizophrenic Disorders1
4Unknown StatusTreatmentBereavement / Depression1
4Unknown StatusTreatmentMajor Depressive Disorder (MDD)2
4WithdrawnTreatmentAdverse Anesthesia Outcome / Nephrostomy; Complications / Regional Anesthesia Morbidity / Upper Urinary Tract Dilatation and Obstruction1
4WithdrawnTreatmentDiabetic Polyneuropathy / Postherpetic Neuralgia1
4WithdrawnTreatmentFibromyalgia1
4WithdrawnTreatmentGynecologic Surgery / Laparoscopy / Quality of Recovery1
Not AvailableActive Not RecruitingNot AvailableAnxiety Disorders / Generalized Anxiety Disorder (GAD) / Obsessive Compulsive Disorder (OCD) / Panic Disorders / Post Traumatic Stress Disorder (PTSD) / Social Anxiety Disorder (SAD)1
Not AvailableActive Not RecruitingNot AvailableMajor Depressive Disorder (MDD)1
Not AvailableActive Not RecruitingBasic ScienceHealthy Volunteers1
Not AvailableCompletedNot AvailableAcute Kidney Injury (AKI) / Depression1
Not AvailableCompletedNot AvailableObsessive Compulsive Disorder (OCD)1
Not AvailableCompletedNot AvailablePain NOS2
Not AvailableCompletedBasic ScienceHealthy Volunteers1
Not AvailableCompletedHealth Services ResearchMajor Depressive Disorder (MDD)1
Not AvailableCompletedPreventionPain NOS1
Not AvailableCompletedTreatmentBack Pain Lower Back1
Not AvailableCompletedTreatmentCancer, Breast1
Not AvailableCompletedTreatmentDepression1
Not AvailableCompletedTreatmentDepressive Disorders1
Not AvailableCompletedTreatmentDiabetes Mellitus (DM) / Painful Neuropathy1
Not AvailableCompletedTreatmentFunction Improvement / Pain Reduction1
Not AvailableCompletedTreatmentLaparoscopic Hysterectomy / Postoperative pain / Postoperative Recovery1
Not AvailableCompletedTreatmentMajor Depressive Disorder (MDD)2
Not AvailableCompletedTreatmentPain NOS1
Not AvailableCompletedTreatmentSpinal Stenosis of Lumbar Region1
Not AvailableCompletedTreatmentSystemic Lupus Erythematosus (SLE)1
Not AvailableCompletedTreatmentTemporomandibular Joint Disorders1
Not AvailableEnrolling by InvitationNot AvailableBipolar Disorder (BD)1
Not AvailableNo Longer AvailableNot AvailableDiabetic Peripheral Neuropathic Pain (DPN) / Fibromyalgia / Generalized Anxiety Disorder (GAD) / Major Depressive Disorder (MDD)1
Not AvailableNot Yet RecruitingTreatmentFibromyalgia / Hyperbaric Oxygen1
Not AvailableNot Yet RecruitingTreatmentOsteoarthritis (OA)1
Not AvailableNot Yet RecruitingTreatmentPain, Acute1
Not AvailableNot Yet RecruitingTreatmentPain, Neuropathic1
Not AvailableRecruitingNot AvailableAnorexia Nervosa (AN) / Attention Deficit Disorder With Hyperactivity (ADHD) / Depression1
Not AvailableRecruitingNot AvailablePregnancy1
Not AvailableRecruitingTreatmentAlcohol-Related Disorders / Brain Injury / Depression / Disease, Chronic / Mild Cognitive Impairment (MCI) / Pain NOS / Posttraumatic Stress Disorders / Quality of Life / Substance-Related Disorders / Suicidal Thoughts / Wounds and Injuries1
Not AvailableRecruitingTreatmentAntidepressant Drug Adverse Reaction / Depression1
Not AvailableRecruitingTreatmentMigraines1
Not AvailableRecruitingTreatmentPain, Acute2
Not AvailableTerminatedNot AvailableChronic Phantom Limb Pain1
Not AvailableTerminatedBasic ScienceFeeling Anxious / Worrying1
Not AvailableTerminatedTreatmentChronic Pain, Postoperative1
Not AvailableTerminatedTreatmentMajor Depressive Disorder (MDD)1
Not AvailableUnknown StatusNot AvailableMajor Depressive Disorder (MDD)1
Not AvailableUnknown StatusBasic ScienceChronic Depression1
Not AvailableUnknown StatusTreatmentFibromyalgia2
Not AvailableUnknown StatusTreatmentMajor Depressive Disorder (MDD)1
Not AvailableUnknown StatusTreatmentTreatment Resistant Depression (TRD)1
Not AvailableWithdrawnTreatmentMajor Depressive Disorder (MDD) / Postpartum Depression1
Not AvailableWithdrawnTreatmentObsessive Compulsive Disorder (OCD)1

Pharmacoeconomics

Manufacturers
  • Eli lilly and co
Packagers
  • Bryant Ranch Prepack
  • Cardinal Health
  • Diversified Healthcare Services Inc.
  • Eli Lilly & Co.
  • Innoviant Pharmacy Inc.
  • Kaiser Foundation Hospital
  • Lake Erie Medical and Surgical Supply
  • Lilly Del Caribe Inc.
  • Murfreesboro Pharmaceutical Nursing Supply
  • Nucare Pharmaceuticals Inc.
  • Palmetto Pharmaceuticals Inc.
  • PD-Rx Pharmaceuticals Inc.
  • Pharmacy Service Center
  • Physicians Total Care Inc.
  • Rebel Distributors Corp.
  • Remedy Repack
  • Resource Optimization and Innovation LLC
  • Southwood Pharmaceuticals
  • Stat Rx Usa
  • Vangard Labs Inc.
Dosage forms
FormRouteStrength
Capsule, delayed releaseOral30 mg
Capsule, delayed releaseOral60 mg
Capsule, delayed releaseOral20 mg/1
Capsule, delayed releaseOral30 mg/1
Capsule, delayed releaseOral60 mg/1
Kit
Capsule, delayed release pelletsOral20 mg/1
Capsule, delayed release pelletsOral30 mg/1
Capsule, delayed release pelletsOral60 mg/1
Capsule, delayed release pelletsOral40 mg/1
Capsule, delayed releaseOral40 mg/1
Capsule, delayed releaseOral20 mg
Capsule, delayed releaseOral40 mg
Prices
Unit descriptionCostUnit
Cymbalta 30 mg Enteric Coated Capsule5.38USD capsule
Cymbalta 60 mg Enteric Coated Capsule5.38USD capsule
Cymbalta 30 mg capsule5.18USD capsule
Cymbalta 60 mg capsule5.18USD capsule
Cymbalta 20 mg Enteric Coated Capsule4.64USD capsule
Cymbalta 20 mg capsule4.62USD capsule
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US5023269No1991-06-112013-06-11Us
CA2344057No2008-11-182019-09-10Canada
CA2153856No2005-05-102015-07-13Canada
US6596756Yes2003-07-222020-03-10Us

Properties

State
Solid
Experimental Properties
PropertyValueSource
logP4Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.00296 mg/mLALOGPS
logP4.72ALOGPS
logP4.2ChemAxon
logS-5ALOGPS
pKa (Strongest Basic)9.7ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area21.26 Å2ChemAxon
Rotatable Bond Count6ChemAxon
Refractivity87.73 m3·mol-1ChemAxon
Polarizability33.15 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+1.0
Blood Brain Barrier+0.9804
Caco-2 permeable+0.6358
P-glycoprotein substrateSubstrate0.7078
P-glycoprotein inhibitor IInhibitor0.5987
P-glycoprotein inhibitor IINon-inhibitor0.5519
Renal organic cation transporterInhibitor0.6525
CYP450 2C9 substrateNon-substrate0.5964
CYP450 2D6 substrateSubstrate0.6482
CYP450 3A4 substrateSubstrate0.5799
CYP450 1A2 substrateInhibitor0.839
CYP450 2C9 inhibitorNon-inhibitor0.7721
CYP450 2D6 inhibitorInhibitor0.6977
CYP450 2C19 inhibitorNon-inhibitor0.572
CYP450 3A4 inhibitorInhibitor0.5108
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.6689
Ames testNon AMES toxic0.5422
CarcinogenicityNon-carcinogens0.9293
BiodegradationNot ready biodegradable0.935
Rat acute toxicity2.5700 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Strong inhibitor0.5926
hERG inhibition (predictor II)Inhibitor0.6386
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-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-qTof , PositiveLC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-qTof , PositiveLC-MS/MSNot Available
MS/MS Spectrum - , positiveLC-MS/MSsplash10-0002-0890000000-a1b4d59cc0496fb3b755
MS/MS Spectrum - , positiveLC-MS/MSsplash10-0002-0970000000-5a3d39a5afda39a4ec23
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-0002-0590000000-894e0be7451e63140e89

Taxonomy

Description
This compound belongs to the class of organic compounds known as naphthalenes. These are compounds containing a naphthalene moiety, which consists of two fused benzene rings.
Kingdom
Organic compounds
Super Class
Benzenoids
Class
Naphthalenes
Sub Class
Not Available
Direct Parent
Naphthalenes
Alternative Parents
Aralkylamines / Alkyl aryl ethers / Thiophenes / Heteroaromatic compounds / Dialkylamines / Organopnictogen compounds / Hydrocarbon derivatives
Substituents
Naphthalene / Alkyl aryl ether / Aralkylamine / Thiophene / Heteroaromatic compound / Secondary aliphatic amine / Ether / Secondary amine / Organoheterocyclic compound / Organooxygen compound
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
duloxetine (CHEBI:36795)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Inhibitor
General Function
Serotonin:sodium symporter activity
Specific Function
Serotonin transporter whose primary function in the central nervous system involves the regulation of serotonergic signaling via transport of serotonin molecules from the synaptic cleft back into t...
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. [PubMed:15695064]
  2. Troelsen KB, Nielsen EO, Mirza NR: Chronic treatment with duloxetine is necessary for an anxiolytic-like response in the mouse zero maze: the role of the serotonin transporter. Psychopharmacology (Berl). 2005 Oct;181(4):741-50. Epub 2005 Sep 29. [PubMed:16032412]
  3. Gould GG, Javors MA, Frazer A: Effect of chronic administration of duloxetine on serotonin and norepinephrine transporter binding sites in rat brain. Biol Psychiatry. 2007 Jan 15;61(2):210-5. Epub 2006 May 2. [PubMed:16650830]
  4. Mirza NR, Nielsen EO, Troelsen KB: Serotonin transporter density and anxiolytic-like effects of antidepressants in mice. Prog Neuropsychopharmacol Biol Psychiatry. 2007 May 9;31(4):858-66. Epub 2007 Jan 30. [PubMed:17335951]
  5. 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. [PubMed:14744476]
  6. 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. [PubMed:9669506]
  7. Karpa KD, Cavanaugh JE, Lakoski JM: Duloxetine pharmacology: profile of a dual monoamine modulator. CNS Drug Rev. 2002 Winter;8(4):361-76. [PubMed:12481192]
  8. van Groeningen CJ, Peters GJ, Pinedo HM: Lack of effectiveness of combined 5-fluorouracil and leucovorin in patients with 5-fluorouracil-resistant advanced colorectal cancer. Eur J Cancer Clin Oncol. 1989 Jan;25(1):45-9. [PubMed:2784100]
  9. Jost W, Marsalek P: Duloxetine: mechanism of action at the lower urinary tract and Onuf's nucleus. Clin Auton Res. 2004 Aug;14(4):220-7. [PubMed:15316838]
  10. Trivedi MH, Desaiah D, Ossanna MJ, Pritchett YL, Brannan SK, Detke MJ: Clinical evidence for serotonin and norepinephrine reuptake inhibition of duloxetine. Int Clin Psychopharmacol. 2008 May;23(3):161-9. doi: 10.1097/YIC.0b013e3282f41d7e. [PubMed:18408530]
  11. Bymaster FP, Lee TC, Knadler MP, Detke MJ, Iyengar S: The dual transporter inhibitor duloxetine: a review of its preclinical pharmacology, pharmacokinetic profile, and clinical results in depression. Curr Pharm Des. 2005;11(12):1475-93. [PubMed:15892657]
  12. Khullar V, Cardozo L, Dmochowski R: Mixed incontinence: current evidence and future perspectives. Neurourol Urodyn. 2010 Apr;29(4):618-22. doi: 10.1002/nau.20907. [PubMed:20432324]
  13. Carter NJ, McCormack PL: Duloxetine: a review of its use in the treatment of generalized anxiety disorder. CNS Drugs. 2009;23(6):523-41. doi: 10.2165/00023210-200923060-00006. [PubMed:19480470]
  14. Hunziker ME, Suehs BT, Bettinger TL, Crismon ML: Duloxetine hydrochloride: a new dual-acting medication for the treatment of major depressive disorder. Clin Ther. 2005 Aug;27(8):1126-43. [PubMed:16199241]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Inhibitor
General Function
Norepinephrine:sodium symporter activity
Specific Function
Amine transporter. Terminates the action of noradrenaline by its high affinity sodium-dependent reuptake into presynaptic terminals.
Gene Name
SLC6A2
Uniprot ID
P23975
Uniprot Name
Sodium-dependent noradrenaline transporter
Molecular Weight
69331.42 Da
References
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
  2. Gould GG, Javors MA, Frazer A: Effect of chronic administration of duloxetine on serotonin and norepinephrine transporter binding sites in rat brain. Biol Psychiatry. 2007 Jan 15;61(2):210-5. Epub 2006 May 2. [PubMed:16650830]
  3. 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. [PubMed:14744476]
  4. 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. [PubMed:9669506]
  5. Vincent S, Bieck PR, Garland EM, Loghin C, Bymaster FP, Black BK, Gonzales C, Potter WZ, Robertson D: Clinical assessment of norepinephrine transporter blockade through biochemical and pharmacological profiles. Circulation. 2004 Jun 29;109(25):3202-7. Epub 2004 Jun 7. [PubMed:15184278]
  6. Schou M, Halldin C, Pike VW, Mozley PD, Dobson D, Innis RB, Farde L, Hall H: Post-mortem human brain autoradiography of the norepinephrine transporter using (S,S)-[18F]FMeNER-D2. Eur Neuropsychopharmacol. 2005 Oct;15(5):517-20. Epub 2005 Apr 7. [PubMed:16139169]
  7. Mirza NR, Nielsen EO, Troelsen KB: Serotonin transporter density and anxiolytic-like effects of antidepressants in mice. Prog Neuropsychopharmacol Biol Psychiatry. 2007 May 9;31(4):858-66. Epub 2007 Jan 30. [PubMed:17335951]
  8. Karpa KD, Cavanaugh JE, Lakoski JM: Duloxetine pharmacology: profile of a dual monoamine modulator. CNS Drug Rev. 2002 Winter;8(4):361-76. [PubMed:12481192]
  9. van Groeningen CJ, Peters GJ, Pinedo HM: Lack of effectiveness of combined 5-fluorouracil and leucovorin in patients with 5-fluorouracil-resistant advanced colorectal cancer. Eur J Cancer Clin Oncol. 1989 Jan;25(1):45-9. [PubMed:2784100]
  10. Jost W, Marsalek P: Duloxetine: mechanism of action at the lower urinary tract and Onuf's nucleus. Clin Auton Res. 2004 Aug;14(4):220-7. [PubMed:15316838]
  11. Trivedi MH, Desaiah D, Ossanna MJ, Pritchett YL, Brannan SK, Detke MJ: Clinical evidence for serotonin and norepinephrine reuptake inhibition of duloxetine. Int Clin Psychopharmacol. 2008 May;23(3):161-9. doi: 10.1097/YIC.0b013e3282f41d7e. [PubMed:18408530]
  12. Bymaster FP, Lee TC, Knadler MP, Detke MJ, Iyengar S: The dual transporter inhibitor duloxetine: a review of its preclinical pharmacology, pharmacokinetic profile, and clinical results in depression. Curr Pharm Des. 2005;11(12):1475-93. [PubMed:15892657]
  13. Khullar V, Cardozo L, Dmochowski R: Mixed incontinence: current evidence and future perspectives. Neurourol Urodyn. 2010 Apr;29(4):618-22. doi: 10.1002/nau.20907. [PubMed:20432324]
  14. Carter NJ, McCormack PL: Duloxetine: a review of its use in the treatment of generalized anxiety disorder. CNS Drugs. 2009;23(6):523-41. doi: 10.2165/00023210-200923060-00006. [PubMed:19480470]
  15. Hunziker ME, Suehs BT, Bettinger TL, Crismon ML: Duloxetine hydrochloride: a new dual-acting medication for the treatment of major depressive disorder. Clin Ther. 2005 Aug;27(8):1126-43. [PubMed:16199241]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Monoamine transmembrane transporter activity
Specific Function
Amine transporter. Terminates the action of dopamine by its high affinity sodium-dependent reuptake into presynaptic terminals.
Gene Name
SLC6A3
Uniprot ID
Q01959
Uniprot Name
Sodium-dependent dopamine transporter
Molecular Weight
68494.255 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423]
  3. Carter NJ, McCormack PL: Duloxetine: a review of its use in the treatment of generalized anxiety disorder. CNS Drugs. 2009;23(6):523-41. doi: 10.2165/00023210-200923060-00006. [PubMed:19480470]
  4. Pereira P, Gianesini J, da Silva Barbosa C, Cassol GF, Von Borowski RG, Kahl VF, Cappelari SE, Picada JN: Neurobehavioral and genotoxic parameters of duloxetine in mice using the inhibitory avoidance task and comet assay as experimental models. Pharmacol Res. 2009 Jan;59(1):57-61. doi: 10.1016/j.phrs.2008.09.014. Epub 2008 Oct 5. [PubMed:18973814]
  5. Hunziker ME, Suehs BT, Bettinger TL, Crismon ML: Duloxetine hydrochloride: a new dual-acting medication for the treatment of major depressive disorder. Clin Ther. 2005 Aug;27(8):1126-43. [PubMed:16199241]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP1A2
Uniprot ID
P05177
Uniprot Name
Cytochrome P450 1A2
Molecular Weight
58293.76 Da
References
  1. Knadler MP, Lobo E, Chappell J, Bergstrom R: Duloxetine: clinical pharmacokinetics and drug interactions. Clin Pharmacokinet. 2011 May;50(5):281-94. doi: 10.2165/11539240-000000000-00000. [PubMed:21366359]
  2. Lobo ED, Bergstrom RF, Reddy S, Quinlan T, Chappell J, Hong Q, Ring B, Knadler MP: In vitro and in vivo evaluations of cytochrome P450 1A2 interactions with duloxetine. Clin Pharmacokinet. 2008;47(3):191-202. [PubMed:18307373]
  3. Authors unspecified: Duloxetine: new indication. Depression and diabetic neuropathy: too many adverse effects. Prescrire Int. 2006 Oct;15(85):168-72. [PubMed:17121211]
  4. Carter NJ, McCormack PL: Duloxetine: a review of its use in the treatment of generalized anxiety disorder. CNS Drugs. 2009;23(6):523-41. doi: 10.2165/00023210-200923060-00006. [PubMed:19480470]
  5. Duloxetine FDA label [File]
Details
2. Cytochrome P450 2D6
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic...
Gene Name
CYP2D6
Uniprot ID
P10635
Uniprot Name
Cytochrome P450 2D6
Molecular Weight
55768.94 Da
References
  1. Knadler MP, Lobo E, Chappell J, Bergstrom R: Duloxetine: clinical pharmacokinetics and drug interactions. Clin Pharmacokinet. 2011 May;50(5):281-94. doi: 10.2165/11539240-000000000-00000. [PubMed:21366359]
  2. Preskorn SH, Nichols AI, Paul J, Patroneva AL, Helzner EC, Guico-Pabia CJ: Effect of desvenlafaxine on the cytochrome P450 2D6 enzyme system. J Psychiatr Pract. 2008 Nov;14(6):368-78. doi: 10.1097/01.pra.0000341891.43501.6b. [PubMed:19057238]
  3. Authors unspecified: Duloxetine: new indication. Depression and diabetic neuropathy: too many adverse effects. Prescrire Int. 2006 Oct;15(85):168-72. [PubMed:17121211]
  4. Carter NJ, McCormack PL: Duloxetine: a review of its use in the treatment of generalized anxiety disorder. CNS Drugs. 2009;23(6):523-41. doi: 10.2165/00023210-200923060-00006. [PubMed:19480470]
  5. Drug Interactions: Cytochrome P450 Drug Interaction Table [Link]
Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Substrate
Inhibitor
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. Chan CY, New LS, Ho HK, Chan EC: Reversible time-dependent inhibition of cytochrome P450 enzymes by duloxetine and inertness of its thiophene ring towards bioactivation. Toxicol Lett. 2011 Oct 30;206(3):314-24. doi: 10.1016/j.toxlet.2011.07.019. Epub 2011 Aug 5. [PubMed:21839818]

Drug created on June 13, 2005 07:24 / Updated on December 10, 2018 13:39