Identification

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

Duloxetine is a dual serotonin and norepinephrine reuptake inhibitor.Label It was originally discovered in 1993 and developed by Eli Lilly and Company as LY248686.15 Duloxetine first received approval from the FDA in August, 2004 as Cymbalta for the treatment of Major Depressive Disorder.20 It has since received approval for a variety of indications including the treatment of neuropathic pain, Generalized Anxiety disorder, osteoarthritis, and stress incontinence. Duloxetine continues to be investigated for the treatment of pain in cancer, surgery, and more.

Structure
Thumb
Synonyms
  • (3S)-N-methyl-3-(1-naphthyloxy)-3-(2-thienyl)propan-1-amine
  • (S)-duloxetine
  • Duloxetina
  • Duloxetine
External IDs
LY 248686 / LY-248686 / LY248686
Product Ingredients
IngredientUNIICASInChI Key
Duloxetine hydrochloride9044SC542W136434-34-9BFFSMCNJSOPUAY-LMOVPXPDSA-N
Product Images
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
AriclaimCapsule, delayed release60 mgOralEli Lilly Nederland B.V.2004-08-112018-08-07Eu
AriclaimCapsule, delayed release30 mgOralEli Lilly Nederland B.V.2004-08-112018-08-07Eu
AriclaimCapsule, delayed release30 mgOralEli Lilly Nederland B.V.2004-08-112018-08-07Eu
AriclaimCapsule, delayed release30 mgOralEli Lilly Nederland B.V.2004-08-112018-08-07Eu
AriclaimCapsule, delayed release60 mgOralEli Lilly Nederland B.V.2004-08-112018-08-07Eu
CymbaltaCapsule, delayed release30 mg/1OralA-S Medication Solutions2004-08-24Not applicableUs54569 594120180907 15195 k45cot
CymbaltaCapsule, delayed release30 mgOralEli Lilly Nederland B.V.2004-12-17Not applicableEu
CymbaltaCapsule, delayed release20 mg/1OralRebel Distributors2004-08-24Not applicableUs
CymbaltaCapsule, delayed release60 mg/1OralPD-Rx Pharmaceuticals, Inc.2010-01-15Not applicableUs
CymbaltaCapsule, delayed release60 mgOralEli Lilly Nederland B.V.2004-12-17Not applicableEu
Additional Data Available
  • Application Number
    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

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  • Product Code
    Product Code

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

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Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Ag-duloxetineCapsule, delayed releaseOralAngita Pharma Inc.2018-07-19Not applicableCanada
Ag-duloxetineCapsule, delayed releaseOralAngita Pharma Inc.2018-07-19Not applicableCanada
Apo-duloxetineCapsule, delayed releaseOralApotex Corporation2016-05-03Not applicableCanada
Apo-duloxetineCapsule, delayed releaseOralApotex Corporation2016-05-03Not applicableCanada
Auro-duloxetineCapsule, delayed releaseOralAuro Pharma Inc2016-05-02Not applicableCanada
Auro-duloxetineCapsule, delayed releaseOralAuro Pharma Inc2016-05-02Not applicableCanada
Dom-duloxetineCapsule, delayed releaseOralDominion PharmacalNot applicableNot applicableCanada
Dom-duloxetineCapsule, delayed releaseOralDominion PharmacalNot applicableNot applicableCanada
DuloxetineCapsule, delayed release20 mg/1OralA-S Medication Solutions2016-08-11Not applicableUs
DuloxetineCapsule, delayed release30 mg/1Oralbryant ranch prepack2013-12-11Not applicableUs
Additional Data Available
  • Application Number
    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

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  • Product Code
    Product Code

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

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Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
DermacinRx DPN PakDuloxetine hydrochloride (60 mg/1) + Levomenthol (30 mg/1mL) + Lidocaine hydrochloride anhydrous (50 mg/1mL)KitTopicalPure Tek Corporation2016-05-262017-08-17Us
International/Other Brands
Dulane / Duzela
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

Indicated for:

1) Management of Major Depressive Disorder.Label

2) Management of Generalized Anxiety Disorder.Label

3) Management of diabetic peripheral neuropathy.Label

4) Management of fibromyalgia.Label

5) Management of chronic musculoskeletal pain.Label

6) Management of osteoarthritis of the knee in adults.17

7) Management of chronic lower back pain in adults.17

8) Management of stress urinary incontinence in adult women.18

Off-label uses include:

1) Management of chemotherapy-induced peripheral neuropathy.8

2) Management of stress urinary incontinence in adult men after prostatectomy until recovery is complete.19

Associated Conditions
Pharmacodynamics

Duloxetine, through increasing serotonin and norepinephrine concentrations in Onuf's nucleus, enhances glutamatergic activation of the pudendal motor nerve which innervates the external urethral sphinter.9,10 This enhanced signaling allows for stronger contraction. Increased contraction of this sphincter increases the pressure needed to produce an incontinence episode in stress urinary incontinence. Duloxetine has been shown to improve Patient Global Impression of Improvement and Incontinence Quality of Life scores.11 It has also been shown to reduce the median incontinence episode frequency at doses of 40 and 80 mg.

Action at the dorsal horn of the spinal cord allows duloxetine to strengthen the the serotonergic and adrenergic pathways involved in descending inhibition of pain.10,12 This results in an increased threshold of activation necessary to transmit painful stimuli to the brain and effective relief of pain, particularly in neuropathic pain. Pain relief has been noted in a variety of painful conditions including diabetic peripheral neuropathy, fibromyalgia, and osteoarthritis using a range of pain assessment surveys.13

While duloxetine has been shown to be effective in both animal models of mood disorders and in clinical trials for the treatment of these disorders in humans, the broad scope of its pharmacodynamic effects on mood regulation in the brain has yet to be explained.14

Increased blood pressure is a common side effect with duloxetine due to vasoconstriction mediated by the intended increase in norepinephrine signaling.Label,16

Mechanism of action

Duloxetine is a potent inhibitor of neuronal serotonin and norepinephrine reuptake and a less potent inhibitor of dopamine reuptake.14 Duloxetine has no significant affinity for dopaminergic, adrenergic, cholinergic, histaminergic, opioid, glutamate, and GABA receptors.

Action on the external urinary sphincter is mediated via duloxetine's CNS effects. Increased serotonin and norepinephrine concentrations in Onuf's nucleus leads to increased activation of 5-HT2, 5-HT3, and α1 adrenergic receptors.9,10 5-HT2 and α1 are both Gq coupled and their activation increases the activity of the inositol trisphosphate/phospholipase C (IP3/PLC) pathway.16 This pathway leads to release of intracellular calcium stores, increasing intracellular calcium concentrations, and facilitating neuronal excitability. 5-HT3 functions as a ligand-gated sodium channel which allows sodium to flow into the neuron when activated. Increased flow of sodium into the neuron contributes to depolarization and activation of voltage gated channels involved in action potential generation. The combined action of these three receptors contributes to increased excitability of the pudendal motor nerve in response to glutamate.

Also related to duloxetine's action at the spinal cord is its modulation of pain. Increasing the concentration of serotonin and norepinephrine in the dorsal horn of the spinal cord increases descending inhibition of pain through activation of 5-HT1A, 5-HT1B, 5-HT1D, 5-HT2, 5-HT3, α1-adrenergic, and α2-adrenergic receptors.12 5-HT2, 5-HT3, and α1-adrenergic mediate neuronal activation as described above. The activated neuron in this case is the GABAergic inhibitory interneuron which synapses onto the nociceptive projection neuron to inhibit the transmission of painful stimuli to the brain. The 5-HT1 and α2 receptors are Gi/Go coupled and their activation leads to increased potassium current through inward rectifier channels and decreased adenylyl cyclase/protein kinase A signaling which contributes to neuronal inhibition.12,16 These inhibitory receptors are present on the projection neuron itself as well as the dorsal root ganglion which precedes it and serves to directly suppress the transmission of painful stimuli.

The mechanisms involved in duloxetine's benefits in depression and anxiety have not been fully elucidated. Dysfunctional serotonin and norepinephrine signaling are thought to be involved and increases in the availability of these neurotransmitters at the synaptic cleft thought to mediate a therapeutic effect.10 It is postulated that the involvement of serotonin and norepinephrine in area responsible for emotional modulation such as the limbic system contributes to the effects in mood disorders specifically but this has yet to be confirmed.

Duloxetine's hypertensive effect is related to its intended pharmacological effect. Increased availability of norepinephrine leads to activation of adrenergic receptors on the vascular endothelium. Since the action of α1 receptors predominates, vasoconstriction results as the Gq coupled receptor mediates calcium release from the sarcoplasmic reticulum to facilitate smooth muscle contraction.16

TargetActionsOrganism
ASodium-dependent serotonin transporter
inhibitor
Humans
ASodium-dependent noradrenaline transporter
inhibitor
Humans
USodium-dependent dopamine transporter
inhibitor
Humans
Additional Data Available
Adverse Effects

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Contraindications

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Blackbox Warnings

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Absorption

Duloxetine is incompletely absorbed with a mean bioavailability of 50% although there is wide variability in the range of 30-80%.7 The population absorption constant (ka) is 0.168 h-1.The molecule is susceptible to hydrolysis in acidic environments necessitating the use of an enteric coating to protect it during transit through the stomach. This creates a 2 hour lag time from administration to the start of absorption. The Tmax is 6 hours including the lag time.Label Administering duloxetine with food 3 hour delay in Tmax along with an 10% decrease in AUC. Similarly, administering the dose at bedtime produces a 4 hour delay and 18% decrease in AUC with a 29% reduction in Cmax.7 These are attributed to delayed gastric emptying in both cases but are not expected to impact therapy to a clinically significant degree.

Volume of distribution

Apparent Vd of 1620-1800 L.Label,7 Duloxetine crosses the blood-brain barrier and collects in the cerebral cortex at a higher concentration than the plasma.7

Protein binding

Over 90% bound to plasma proteins, primarily albumin and α1 acid-glycoprotein.Label,7

Metabolism

Duloxetine is extensively metabolized primarily by CYP1A2 and CYP2D6 with the former being the greater contributor.Label,7 It is hydroxylated at the 4, 5, or 6 positions on the naphthalene ring with the 4-hydroxy metabolite proceeding directly to a glucuronide conjugate while the 5 and 6-hydroxy metabolites proceed through a catechol and a 5-hydroxy, 6-methoxy intermediate before undergoing glucuronide or sulfate conjugation. CYP2C9 is known to be a minor contributor to the 5-hydroxy metabolite. Another uncharacterized metabolite is known to be excreted in the feces but comprises <5% of the total excreted drug. Many other metabolites exist but have not been identified due their low contribution to the overall profile of duloxetine and lack of clinical significance.

Route of elimination

About 70% of duloxetine is excreted in the urine mainly as conjugated metabolites.Label Another 20% is present in the feces as the parent drug, 4-hydroxy metabolite, and an uncharacterized metabolite.Label,7 Biliary secretion is thought to play a role due to timeline of fecal excretion exceeding the time expected of normal GI transit.7

Half life

Mean of 12 h with a range of 8-17.Label,7

Clearance

There is a large degree of interindividual variation reported in the clearance of duloxetine with values ranging from 57-114 L/h.7 Steady state concentrations have still been shown to be dose proportional with a doubling of dose from 30 to 60 mg and from 60 to 120 mg producing 2.3 and 2.6 times the Css respectively.

Toxicity

Overdose

Fatalities have been reported with doses of 1000mg involving both mixed drugs as well as duloxetine alone.Label Signs and symptoms of overdose include: somnolence, coma, serotonin syndrome, seizure, syncope, hypo- or hypertension, tachycardia, and vomiting. No antidote exists and the drug is unlikely to be cleared by hemodialysis. Supportive care is recommended along with activated charcoal and gastric lavage to reduce absorption. If serotonin syndrome occurs specific treatment such as temperature control or cyproheptadine may be initiated.

Carcinogenicity & Mutagenicity

Increased incidence of hepatocellular carcinomas and adenomas were reported in female mice fed 140 mg/kg/day duloxetine for 2 years, equivalent to 6 times the maximum recommended human dose (MRHD).Label No effect was reported with doses of 50mg/kg/day (2 time MRHD) in females or 100 mg/kg/day in males (4 times MRHD). Similar investigation in rats produced no carcinogenicity at doses of 27 mg/kg/day (2 times MRHD)in females and 36 mg/kg/day in males (4 times MRHD).

No mutagenicity, clastogenicity, induction of sister chromatid exchange, or genotoxicity has been observed in toxicology investigations.

Reproductive Toxicity

Neither male or female rats displayed adverse reproductive effects at doses up to 45 mg/kg/day (4 times MRHD).Label

Lactation

An estimated 25% of plasma duloxetine appears in breast milk with the estimated daily infant dose being 0.14% of the maternal dose.Label Breast milk concentrations have been observed to peak 3 hours after administration.

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
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
(R)-warfarinThe serum concentration of (R)-warfarin can be increased when it is combined with Duloxetine.
(S)-WarfarinThe serum concentration of (S)-Warfarin can be increased when it is combined with Duloxetine.
1-(2-Phenylethyl)-4-phenyl-4-acetoxypiperidineThe metabolism of Duloxetine can be decreased when combined with 1-(2-Phenylethyl)-4-phenyl-4-acetoxypiperidine.
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.
3,5-diiodothyropropionic acidThe therapeutic efficacy of 3,5-diiodothyropropionic acid can be decreased when used in combination with Duloxetine.
3,5-DiiodotyrosineThe therapeutic efficacy of 3,5-Diiodotyrosine can be decreased when used in combination with Duloxetine.
4-Bromo-2,5-dimethoxyamphetamineThe risk or severity of adverse effects can be increased when Duloxetine is combined with 4-Bromo-2,5-dimethoxyamphetamine.
4-Bromo-2,5-dimethoxyphenethylamineDuloxetine may increase the tachycardic activities of 4-Bromo-2,5-dimethoxyphenethylamine.
Additional Data Available
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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]
  7. 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]
  8. Hershman DL, Lacchetti C, Loprinzi CL: Prevention and Management of Chemotherapy-Induced Peripheral Neuropathy in Survivors of Adult Cancers: American Society of Clinical Oncology Clinical Practice Guideline Summary. J Oncol Pract. 2014 Nov;10(6):e421-e424. doi: 10.1200/JOP.2014.001776. [PubMed:29424607]
  9. de Groat WC, Yoshimura N: Pharmacology of the lower urinary tract. Annu Rev Pharmacol Toxicol. 2001;41:691-721. doi: 10.1146/annurev.pharmtox.41.1.691. [PubMed:11264473]
  10. Thor KB, Kirby M, Viktrup L: Serotonin and noradrenaline involvement in urinary incontinence, depression and pain: scientific basis for overlapping clinical efficacy from a single drug, duloxetine. Int J Clin Pract. 2007 Aug;61(8):1349-55. doi: 10.1111/j.1742-1241.2007.01433.x. Epub 2007 Jun 30. [PubMed:17608681]
  11. Basu M, Duckett J: The treatment of urinary incontinence with Duloxetine. J Obstet Gynaecol. 2008 Feb;28(2):166-9. doi: 10.1080/01443610801912931. [PubMed:18393011]
  12. Millan MJ: Descending control of pain. Prog Neurobiol. 2002 Apr;66(6):355-474. [PubMed:12034378]
  13. Bellingham GA, Peng PW: Duloxetine: a review of its pharmacology and use in chronic pain management. Reg Anesth Pain Med. 2010 May-Jun;35(3):294-303. doi: 10.1097/AAP.0b013e3181df2645. [PubMed:20921842]
  14. Gupta S, Nihalani N, Masand P: Duloxetine: review of its pharmacology, and therapeutic use in depression and other psychiatric disorders. Ann Clin Psychiatry. 2007 Apr-Jun;19(2):125-32. doi: 10.1080/10401230701333319. [PubMed:17612852]
  15. Wong DT, Bymaster FP, Mayle DA, Reid LR, Krushinski JH, Robertson DW: LY248686, a new inhibitor of serotonin and norepinephrine uptake. Neuropsychopharmacology. 1993 Jan;8(1):23-33. doi: 10.1038/npp.1993.4. [PubMed:8424846]
  16. David R. Sibley; Lisa A. Hazelwood; Susan G. Amara (2018). 13. In Goodman & Gilman's: The Pharmacological Basis of Therapeutics (13th ed.). McGraw-Hill Education. [ISBN:978-1-25-958473-2]
  17. Cymbalta Health Canada Monograph [Link]
  18. Yentreve EMA SmPC [Link]
  19. EAU Stress Urinary Incontinence Guidelines [Link]
  20. Original FDA Label Cymbalta [Link]
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
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 ScienceStroke1
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
1CompletedOtherMajor Depressive Disorder (MDD)1
1CompletedTreatmentHealthy Volunteers3
1CompletedTreatmentHealthy Volunteers / Hyperalgesia1
1CompletedTreatmentMajor Depressive Disorder (MDD)1
1RecruitingBasic ScienceAlcohol Use Disorder (AUD)1
1RecruitingBasic ScienceMethamphetamine Use Disorder1
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
2CompletedTreatmentMajor Depressive Disorder (MDD)4
2CompletedTreatmentPain, Neuropathic / Peripheral neuropathy1
2CompletedTreatmentUrinary Incontinence (UI)1
2CompletedTreatmentUrinary Stress Incontinence2
2Not Yet RecruitingTreatmentChemotherapy-induced Peripheral Neuropathy (CIPN)1
2Not Yet RecruitingTreatmentDepression / Knee Osteoarthritis (Knee OA)1
2RecruitingPreventionPain, Neuropathic1
2RecruitingTreatmentGulf War Illness1
2RecruitingTreatmentOrthopaedic Related Pain (Musculoskeletal Pain)1
2RecruitingTreatmentPain1
2TerminatedTreatmentBack Pain Lower Back1
2TerminatedTreatmentDepression / Traumatic Brain Injury (TBI)1
2TerminatedTreatmentDiabetic Neuropathic Pain1
2TerminatedTreatmentHuman Immunodeficiency Virus (HIV) Infections / Peripheral neuropathy1
2TerminatedTreatmentMajor Depressive Disorder (MDD)2
2WithdrawnTreatmentPainful Diabetic Neuropathy (PDN)1
2WithdrawnTreatmentParkinson's Disease (PD)1
2, 3CompletedPreventionPostoperative Myalgia1
2, 3CompletedTreatmentDepressive Symptomatology1
2, 3CompletedTreatmentDiabetes Mellitus (DM) / Peripheral neuropathy1
2, 3CompletedTreatmentDisseminated Sclerosis1
2, 3CompletedTreatmentFatigue Syndrome, Chronic1
2, 3CompletedTreatmentMajor Depressive Disorder (MDD)1
2, 3Not Yet RecruitingSupportive CareStage II Colorectal Cancer AJCC v8 / Stage III Colorectal Cancer AJCC v81
3CompletedBasic ScienceParkinson's Disease (PD)1
3CompletedBasic SciencePost-gastrointestinal bypass surgery1
3CompletedPreventionPost Laparoscopic Shoulder Pain1
3CompletedSupportive CareNeurologic toxicity / Pain / Peripheral neuropathy / Unspecified Adult Solid Tumor, Protocol Specific1
3CompletedTreatmentAnxiety1
3CompletedTreatmentAnxiety Disorders5
3CompletedTreatmentAnxiety States, Neurotic / Neuroses, Anxiety1
3CompletedTreatmentBack Pain Lower Back Chronic3
3CompletedTreatmentBack Pain Without Radiation2
3CompletedTreatmentBreast Cancer / Musculoskeletal Complications / Pain1
3CompletedTreatmentCognition / Depression1
3CompletedTreatmentDepression1
3CompletedTreatmentDepression / Depressive Disorders / Major Depressive Disorder (MDD)1
3CompletedTreatmentDepression / Depressive Disorders / Major Depressive Disorder (MDD) / Moods Disorders / Psychiatric Disorder NOS1
3CompletedTreatmentDepression / Pain1
3CompletedTreatmentDepressive Disorder, Treatment-Resistant / Major depressive disorder, recurrent episode2
3CompletedTreatmentDepressive Disorders1
3CompletedTreatmentDiabetic Neuropathies3
3CompletedTreatmentDiabetic Neuropathy, Painful3
3CompletedTreatmentDisseminated Sclerosis1
3CompletedTreatmentFibromyalgia7
3CompletedTreatmentFibromyalgia / Human Immunodeficiency Virus Type 1 (HIV-1) Infection1
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
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
3WithdrawnTreatmentDepressive Disorder, Treatment-Resistant1
4Active Not RecruitingBasic ScienceMajor Depressive Disorder (MDD)1
4Active Not RecruitingSupportive CareIntervertebral Disc Degeneration1
4Active Not RecruitingTreatmentDepressive Disorder, NOS / Dysthymic Disorder / Major Depressive Disorder (MDD)1
4CompletedBasic ScienceHealthy Volunteers1
4CompletedBasic ScienceHealthy Volunteers / Major Depressive Disorder (MDD)1
4CompletedBasic ScienceOsteoarthritis (OA)1
4CompletedOtherHealthy Controls / Major Depressive Disorder (MDD)1
4CompletedOtherPain, Neuropathic1
4CompletedPreventionMigraine1
4CompletedSupportive CareDepression / Mild Cognitive Impairment (MCI)1
4CompletedTreatmentAgeing / Back Pain, Unspecified / 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
4CompletedTreatmentDepression5
4CompletedTreatmentDepression / Dysthymic Disorder1
4CompletedTreatmentDepression / Menopause / Vasomotor Symptoms1
4CompletedTreatmentDepressive Disorder NOS / Dysthymic Disorder1
4CompletedTreatmentDepressive Disorders1
4CompletedTreatmentDiabetic Neuropathies1
4CompletedTreatmentDiabetic Neuropathies / Major Depressive Disorder (MDD)1
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 / Soft Tissue Discomfort Syndrome1
4CompletedTreatmentObsessive Compulsive Disorder (OCD)1
4CompletedTreatmentOsteoarthritis (OA) / Pain1
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 RecruitingTreatmentDiagnosis and Treatment of Depression1
4Not Yet RecruitingTreatmentKnee Osteoarthritis (Knee OA)1
4Not Yet RecruitingTreatmentKnee Osteoarthritis (Knee OA) / Pain, Chronic1
4RecruitingNot AvailableDepressive Disorders / Lactation1
4RecruitingBasic ScienceNone (i.e. Healthy Volunteers)1
4RecruitingHealth Services ResearchPain, Chronic1
4RecruitingOtherBack Pain Lower Back Chronic / Neck Pain Chronic1
4RecruitingOtherDepression / Men Infertility1
4RecruitingTreatmentDepression / Hearing loss or impairment1
4RecruitingTreatmentPost-thoracotomy Pain1
4TerminatedPreventionDepression1
4TerminatedTreatmentBack Pain Lower Back Chronic / Diabetic Neuropathic Pain1
4TerminatedTreatmentDepression1
4TerminatedTreatmentPelvis Pain Chronic1
4Unknown StatusBasic ScienceMajor Depressive Disorder (MDD)1
4Unknown StatusDiagnosticSchizophrenic Disorders1
4Unknown StatusTreatmentBereavement / Depression1
4Unknown StatusTreatmentMajor Depressive Disorder (MDD)2
4WithdrawnOtherHealthy Volunteers2
4WithdrawnTreatmentDiabetic Polyneuropathy / Postherpetic Neuralgia1
4WithdrawnTreatmentFibromyalgia2
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 AvailableCompletedNot AvailableAcute Kidney Injury (AKI) / Depression1
Not AvailableCompletedNot AvailableAnorexia Nervosa (AN) / Attention Deficit Disorder With Hyperactivity (ADHD) / Depression1
Not AvailableCompletedNot AvailableObsessive Compulsive Disorder (OCD)1
Not AvailableCompletedNot AvailablePain2
Not AvailableCompletedBasic ScienceHealthy Volunteers2
Not AvailableCompletedHealth Services ResearchMajor Depressive Disorder (MDD)1
Not AvailableCompletedPreventionPain1
Not AvailableCompletedTreatmentBack Pain Lower Back1
Not AvailableCompletedTreatmentBreast Cancer1
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 AvailableCompletedTreatmentMigraine1
Not AvailableCompletedTreatmentPain1
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 RecruitingTreatmentKnee Osteoarthritis (Knee OA)1
Not AvailableNot Yet RecruitingTreatmentOsteoarthritis (OA)1
Not AvailableNot Yet RecruitingTreatmentPain, Acute1
Not AvailableRecruitingNot AvailablePregnancy1
Not AvailableRecruitingTreatmentAlcohol-Related Disorders / Brain Injury / Depression / Disease, Chronic / Mild Cognitive Impairment (MCI) / Pain / Posttraumatic Stress Disorders / Quality of Life / Substance-Related Disorders / Suicidal Thoughts / Wounds and Injuries1
Not AvailableRecruitingTreatmentAntidepressant Drug Adverse Reaction / Depression1
Not AvailableRecruitingTreatmentPain, Acute2
Not AvailableRecruitingTreatmentPain, Neuropathic1
Not AvailableTerminatedNot AvailableChronic Phantom Limb Pain1
Not AvailableTerminatedBasic ScienceAnxiety / 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 releaseOral
Capsule, delayed releaseOral20 mg/1
Capsule, delayed releaseOral30 mg/1
Capsule, delayed releaseOral60 mg/1
KitTopical
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 releaseOral30 mg
Capsule, delayed releaseOral60 mg
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
US9839626No2017-04-132037-04-13Us
Additional Data Available
  • Filed On
    Filed On

    The date on which a patent was filed with the relevant government.

    Learn more

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
Humans
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
Humans
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
Humans
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
Humans
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
Humans
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. Flockhart Table of Drug Interactions [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Steroid 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 oxidizes a variety of structurally un...
Gene Name
CYP2C9
Uniprot ID
P11712
Uniprot Name
Cytochrome P450 2C9
Molecular Weight
55627.365 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]

Carriers

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Ligand
General Function
Toxic substance binding
Specific Function
Serum albumin, the main protein of plasma, has a good binding capacity for water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs. Its main function is the regulation of the colloid...
Gene Name
ALB
Uniprot ID
P02768
Uniprot Name
Serum albumin
Molecular Weight
69365.94 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]
Kind
Protein group
Organism
Humans
Pharmacological action
Unknown
Actions
Ligand
General Function
Not Available
Specific Function
Functions as transport protein in the blood stream. Binds various ligands in the interior of its beta-barrel domain. Also binds synthetic drugs and influences their distribution and availability in...

Components:
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]

Transporters

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Xenobiotic-transporting atpase activity
Specific Function
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
Gene Name
ABCB1
Uniprot ID
P08183
Uniprot Name
Multidrug resistance protein 1
Molecular Weight
141477.255 Da
References
  1. Ruike Z, Junhua C, Wenxing P: In vitro and in vivo evaluation of the effects of duloxetine on P-gp function. Hum Psychopharmacol. 2010 Nov;25(7-8):553-9. doi: 10.1002/hup.1152. [PubMed:21312289]

Drug created on June 13, 2005 07:24 / Updated on December 08, 2019 20:10