Duloxetine (CHEM002207)

IdentificationTaxonomyBiological PropertiesPhysical PropertiesToxicity ProfileSpectraConcentrationsLinksReferencesTargets (3)XML
Record Information
Version1.0
Creation Date2009-07-21 20:27:00 UTC
Update Date2026-05-14 16:39:58 UTC
Accession NumberCHEM002207
Identification
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.
Contaminant Sources
  • HMDB Contaminants - Urine
  • STOFF IDENT Compounds
  • T3DB toxins
  • ToxCast & Tox21 Chemicals
Contaminant Type
  • Adrenergic Uptake Inhibitor
  • Amine
  • Antidepressant
  • Dopamine Uptake Inhibitor
  • Drug
  • Ether
  • Metabolite
  • Organic Compound
  • Serotonin Uptake Inhibitor
  • Synthetic Compound
Chemical Structure
Thumb
MOLSDFPDBSMILESInChI
Synonyms
ValueSource
(3S)-N-Methyl-3-(1-naphthyloxy)-3-(2-thienyl)propan-1-amineChEBI
LY 248686ChEBI
YentreveKegg
Duloxetine HCLHMDB
Hydrochloride, duloxetineHMDB
Duloxetine hydrochlorideHMDB
Duloxetine ethanedioate (1:1), (+-)-isomer - T353987HMDB
N-Methyl-3-(1-naphthalenyloxy)-2-thiophenepropanamineHMDB
CymbaltaHMDB
HCL, DuloxetineHMDB
N-Methyl-3-(1-naphthalenyloxy)-3-(2-thiophene)propanamideHMDB
Duloxetine, (+)-isomerHMDB
DuloxetineMeSH
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
SMILESCNCC[C@H](OC1=CC=CC2=CC=CC=C12)C1=CC=CS1
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
InChI KeyZEUITGRIYCTCEM-KRWDZBQOSA-N
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
ClassNaphthalenes
Sub ClassNot Available
Direct ParentNaphthalenes
Alternative Parents
Substituents
  • 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
OriginExogenous
Cellular Locations
  • Membrane
Biofluid LocationsNot Available
Tissue LocationsNot Available
PathwaysNot Available
Applications
Biological RolesNot Available
Chemical RolesNot Available
Physical Properties
StateSolid
AppearanceWhite powder.
Experimental Properties
PropertyValue
Melting PointNot Available
Boiling PointNot Available
Solubility2.96e-03 g/L
Predicted Properties
PropertyValueSource
Water Solubility0.003 g/LALOGPS
logP4.72ALOGPS
logP4.2ChemAxon
logS-5ALOGPS
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
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash KeyView
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, Positivesplash10-0006-9530000000-49ea61eaf551272fdf2bSpectrum
Predicted GC-MSPredicted GC-MS Spectrum - GC-MS (Non-derivatized) - 70eV, PositiveNot AvailableSpectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-qTof , Positivesplash10-0002-0890000000-a1b4d59cc0496fb3b755Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-qTof , Positivesplash10-0002-0970000000-5a3d39a5afda39a4ec23Spectrum
LC-MS/MSLC-MS/MS Spectrum - , positivesplash10-0002-0890000000-a1b4d59cc0496fb3b755Spectrum
LC-MS/MSLC-MS/MS Spectrum - , positivesplash10-0002-0970000000-5a3d39a5afda39a4ec23Spectrum
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QFT , positivesplash10-0002-0590000000-894e0be7451e63140e89Spectrum
LC-MS/MSLC-MS/MS Spectrum - 35V, Positivesplash10-0006-9000000000-f8c67ea645eec49b2c3eSpectrum
LC-MS/MSLC-MS/MS Spectrum - 35V, Positivesplash10-0002-0590000000-894e0be7451e63140e89Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-00kb-0090000000-79dbcab4853aa7d19624Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-014m-4290000000-a13b02643710fd4db48fSpectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-05tf-5910000000-9993fd40535267373a45Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-0002-1390000000-1f24878e7debb65a5c43Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-0005-3390000000-39a64a08f599b40173a6Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0a4l-8910000000-3949e7d24fa4c4d4757aSpectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-0002-0890000000-1a0428116fbabd8d95d4Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-0002-1960000000-91680eff5f6acae59b5aSpectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-00ov-2910000000-664e6f8f3a608f6cb53fSpectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-0002-0190000000-1263586eab6bc5fb17ffSpectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-000x-6910000000-78b5f700d18c7c60b0bbSpectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-0006-1900000000-df1c429b62c077911edfSpectrum
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 (1).
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)
Concentrations
Not Available
DrugBank IDDB00476
HMDB IDHMDB0014619
FooDB IDNot Available
Phenol Explorer IDNot Available
KNApSAcK IDNot Available
BiGG IDNot Available
BioCyc IDNot Available
METLIN IDNot Available
PDB IDNot Available
Wikipedia LinkDuloxetine
Chemspider ID54822
ChEBI ID36795
PubChem Compound ID60835
Kegg Compound IDNot Available
YMDB IDNot Available
ECMDB IDNot Available
References
Synthesis Reference

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

MSDSLink
General References
1. 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.
2. 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.
3. Anttila S, Leinonen E: Duloxetine Eli Lilly. Curr Opin Investig Drugs. 2002 Aug;3(8):1217-21.
4. Karpa KD, Cavanaugh JE, Lakoski JM: Duloxetine pharmacology: profile of a dual monoamine modulator. CNS Drug Rev. 2002 Winter;8(4):361-76.
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.
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.