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Record Information
Creation Date2009-07-21 20:27:00 UTC
Update Date2014-12-24 20:25:51 UTC
Accession NumberT3D2805
Common NameDuloxetine
ClassSmall Molecule
DescriptionDuloxetine (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.
Compound Type
  • Adrenergic Uptake Inhibitor
  • Amine
  • Antidepressant
  • Dopamine Uptake Inhibitor
  • Drug
  • Ether
  • Metabolite
  • Organic Compound
  • Serotonin Uptake Inhibitor
  • Synthetic Compound
Chemical Structure
LY 248686
Chemical FormulaC18H19NOS
Average Molecular Mass297.415 g/mol
Monoisotopic Mass297.119 g/mol
CAS Registry Number136434-34-9
IUPAC Namemethyl[(3S)-3-(naphthalen-1-yloxy)-3-(thiophen-2-yl)propyl]amine
Traditional Nameduloxetine
InChI IdentifierInChI=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
Chemical Taxonomy
Description belongs to the class of organic compounds known as naphthalenes. Naphthalenes are compounds containing a naphthalene moiety, which consists of two fused benzene rings.
KingdomOrganic compounds
Super ClassBenzenoids
Sub ClassNot Available
Direct ParentNaphthalenes
Alternative Parents
  • Naphthalene
  • Alkyl aryl ether
  • Aralkylamine
  • Thiophene
  • Heteroaromatic compound
  • Secondary aliphatic amine
  • Ether
  • Secondary amine
  • Organoheterocyclic compound
  • Organooxygen compound
  • Organonitrogen compound
  • Organic oxygen compound
  • Amine
  • Organopnictogen compound
  • Organic nitrogen compound
  • Hydrocarbon derivative
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors
Biological Properties
StatusDetected and Not Quantified
Cellular Locations
  • Membrane
Biofluid LocationsNot Available
Tissue LocationsNot Available
PathwaysNot Available
Biological RolesNot Available
Chemical RolesNot Available
Physical Properties
AppearanceWhite powder.
Experimental Properties
Melting PointNot Available
Boiling PointNot Available
Solubility2.96e-03 g/L
Predicted Properties
Water Solubility0.003 g/LALOGPS
pKa (Strongest Basic)9.7ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area21.26 ŲChemAxon
Rotatable Bond Count6ChemAxon
Refractivity87.73 m³·mol⁻¹ChemAxon
Polarizability33.15 ųChemAxon
Number of Rings3ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectrum TypeDescriptionSplash KeyDeposition DateView
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-0006-9530000000-49ea61eaf551272fdf2b2017-09-01View Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, PositiveNot Available2021-10-12View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-qTof , Positivesplash10-0002-0890000000-a1b4d59cc0496fb3b7552017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-qTof , Positivesplash10-0002-0970000000-5a3d39a5afda39a4ec232017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - , positivesplash10-0002-0890000000-a1b4d59cc0496fb3b7552017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - , positivesplash10-0002-0970000000-5a3d39a5afda39a4ec232017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-0002-0590000000-894e0be7451e63140e892017-09-14View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 35V, Positivesplash10-0006-9000000000-f8c67ea645eec49b2c3e2021-09-20View Spectrum
LC-MS/MSLC-MS/MS Spectrum - 35V, Positivesplash10-0002-0590000000-894e0be7451e63140e892021-09-20View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-00kb-0090000000-79dbcab4853aa7d196242016-06-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-014m-4290000000-a13b02643710fd4db48f2016-06-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-05tf-5910000000-9993fd40535267373a452016-06-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-0002-1390000000-1f24878e7debb65a5c432016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0005-3390000000-39a64a08f599b40173a62016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0a4l-8910000000-3949e7d24fa4c4d4757a2016-08-03View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-0002-0890000000-1a0428116fbabd8d95d42021-09-23View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0002-1960000000-91680eff5f6acae59b5a2021-09-23View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-00ov-2910000000-664e6f8f3a608f6cb53f2021-09-23View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-0002-0190000000-1263586eab6bc5fb17ff2021-09-24View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-000x-6910000000-78b5f700d18c7c60b0bb2021-09-24View Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0006-1900000000-df1c429b62c077911edf2021-09-24View Spectrum
Toxicity Profile
Route of ExposureOrally administered duloxetine hydrochloride is well absorbed.
Mechanism of ToxicityDuloxetine 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.
MetabolismThe 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)
Toxicity ValuesOral, rat LD50: 491 mg/kg for males and 279 mg/kg for females (3).
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesFor 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.
Minimum Risk LevelNot Available
Health EffectsNot Available
SymptomsSymptoms of overdose include tremors, convulsions, reduced activity, slow pupillary response, intermittent tremors, and rigidity.
TreatmentThere is no specific antidote to Duloxetine, but if serotonin syndrome ensues, specific treatment (such as with cyproheptadine and/or temperature control) may be considered. In case of acute overdose, treatment should consist of those general measures employed in the management of overdose with any drug. An adequate airway, oxygenation, and ventilation should be assured, and cardiac rhythm and vital signs should be monitored. Induction of emesis is not recommended. Gastric lavage with a large-bore orogastric tube with appropriate airway protection, if needed, may be indicated if performed soon after ingestion or in symptomatic patients. Activated charcoal may be useful in limiting absorption of duloxetine from the gastrointestinal tract. Administration of activated charcoal has been shown to decrease AUC and Cmax by an average of one-third, although some subjects had a limited effect of activated charcoal. Due to the large volume of distribution of this drug, forced diuresis, dialysis, hemoperfusion, and exchange transfusion are unlikely to be beneficial. (9)
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDDB00476
PubChem Compound ID60835
ChemSpider ID54822
KEGG IDNot Available
UniProt IDNot Available
ChEBI ID36795
BioCyc IDNot Available
CTD IDNot Available
Stitch IDDuloxetine
PDB IDNot Available
ACToR IDNot Available
Wikipedia LinkDuloxetine
Synthesis Reference

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

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. [11282251 ]
  2. Anttila S, Leinonen E: Duloxetine Eli Lilly. Curr Opin Investig Drugs. 2002 Aug;3(8):1217-21. [12211418 ]
  3. Wishart DS, Knox C, Guo AC, Cheng D, Shrivastava S, Tzur D, Gautam B, Hassanali M: DrugBank: a knowledgebase for drugs, drug actions and drug targets. Nucleic Acids Res. 2008 Jan;36(Database issue):D901-6. Epub 2007 Nov 29. [18048412 ]
  4. Karpa KD, Cavanaugh JE, Lakoski JM: Duloxetine pharmacology: profile of a dual monoamine modulator. CNS Drug Rev. 2002 Winter;8(4):361-76. [12481192 ]
  5. 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. [2784100 ]
  6. 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. [15316838 ]
  7. 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. [19480470 ]
  8. [Link]
  9. RxList: The Internet Drug Index (2009). [Link]
Gene Regulation
Up-Regulated GenesNot Available
Down-Regulated GenesNot Available


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:
Uniprot ID:
Molecular Weight:
69331.42 Da
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [11752352 ]
  2. 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. [14744476 ]
  3. Beique JC, Lavoie N, de Montigny C, Debonnel G: Affinities of venlafaxine and various reuptake inhibitors for the serotonin and norepinephrine transporters. Eur J Pharmacol. 1998 May 15;349(1):129-32. [9669506 ]
  4. 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. [16650830 ]
  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. [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. [16139169 ]
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 the pre-synaptic terminal for re-utilization. Plays a key role in mediating regulation of the availability of serotonin to other receptors of serotonergic systems. Terminates the action of serotonin and recycles it in a sodium-dependent manner.
Gene Name:
Uniprot ID:
Molecular Weight:
70324.165 Da
  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. [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. [16032412 ]
  3. 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. [17335951 ]
  4. 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. [16650830 ]
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:
Uniprot ID:
Molecular Weight:
68494.255 Da
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [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. [17016423 ]