Drug Details

General Information of the Drug (ID: DR3634)
Name
Duloxetine
Synonyms
duloxetine; 116539-59-4; (S)-Duloxetine; Cymbalta; Yentreve; (S)-N-Methyl-3-(naphthalen-1-yloxy)-3-(thiophen-2-yl)propan-1-amine; LY 248686; 136434-34-9; UNII-O5TNM5N07U; Ariclaim; Xeristar; LY248686; Yentreve (TN); (3S)-N-methyl-3-naphthalen-1-yloxy-3-thiophen-2-ylpropan-1-amine; O5TNM5N07U; 2-Thiophenepropanamine, N-methyl-gamma-(1-naphthalenyloxy)-, (gammaS)-; N-Methyl-gama-(1-naphthalenyloxy)-2-thiophenepropanamine; CHEBI:36795; (3S)-N-methyl-3-(1-naphthyloxy)-3-(2-thienyl)propan-1-amine; MFCD06801358; LY-248686; methyl[(3S)-3-(naphthalen-1-yloxy)-3-(thiophen-2-yl)propyl]amine; (3s)-N-Methyl-3-(Naphthalen-1-Yloxy)-3-(Thiophen-2-Yl)propan-1-Amine; Duloxetine [INN:BAN]; Duloxetine (INN); SMR000449282; HSDB 7368; NCGC00164559-01; Duloxetine Boehringer Ingelheim; (S)-N-Methyl-gamma-(1-naphthalenyloxy)-2-thiophenepropanamine; 29E; CPD000449282; SCHEMBL8291; CHEMBL1175; GTPL202; cc-636; MLS000758267; MLS001423946; (S)-Duloxetine;LY248686; DTXSID6048385; BDBM84745; HMS2051I05; HMS3886K11; HY-B0161; ZINC1536779; (3S)-N-methyl-3-(naphthalen-1-yloxy)-3-(2-thienyl)propan-1-amine; 2-Thiophenepropanamine, N-methyl-gamma-(1-naphthalenyloxy)-, (S)-; ANW-63714; PDSP1_000969; PDSP1_001385; PDSP2_000953; PDSP2_001369; s5071; AKOS015851058; CCG-100763; CM14423; DB00476; NC00013; SB19317; VA11973; NCGC00164559-02; NCGC00164559-04; AC-15704; AS-35259; SBI-0206832.P001; CAS_136434-34-9; D07880; AB00639911-13; AB00639911_15; AB00639911_16; 539D594; Q411932; J-003455; J-523680; (+)-(S)-N-Methyl-3-(1-naphthyloxy)-3-(2-thienyl)propylamin; (S)-(+)-N-methyl-3-(1-naphthyloxy)-3-(2-thienyl)propylamine; (S)-N-methyl-3-(1-naphthalenyloxy)-3-(2-thienyl) propanamine; (3S)-N-methyl-3-naphthalen-1-yloxy-3-thiophen-2-yl-propan-1 amine; (3S)-N-methyl-3-naphthalen-1-yloxy-3-thiophen-2-yl-propan-1-amine; (3s)-n-methyl-3-naphthalen-1-yloxy-3-thiophen-2-yl-propan-1amine; (S)-(+)-N-methyl-3-(1-naphthaleneoxy)-3-(2-thienyl)propanamine
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Molecular Type
Small molecule
Disease Depression [ICD-11: 6A70-6A71] Approved [1]
Structure
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2D MOL

3D MOL

ADMET Property
Absorption Tmax
The time to maximum plasma concentration (Tmax) is 6 h
BDDCS Class
Biopharmaceutics Drug Disposition Classification System (BDDCS) Class 1: high solubility and high permeability
Bioavailability
The bioavailability of drug is 50%
Clearance
The clearance of drug is 57-114 L/h
Elimination
About 70% of duloxetine is excreted in the urine mainly as conjugated metabolites
Half-life
The concentration or amount of drug in body reduced by one-half in 12 hours
Metabolism
The drug is metabolized via the CYP1A2 and CYP2D6 with the former being the greater contributor
MRTD
The Maximum Recommended Therapeutic Dose (MRTD) of drug that ensured maximising efficacy and moderate side effect is 2.882 micromolar/kg/day
Unbound Fraction
The unbound fraction of drug in plasma is 0.04%
Vd
The volume of distribution (Vd) of drug is 1620-1800 L
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    Click to Show/Hide the Molecular Information and External Link(s) of This Natural Product
Formula
C18H19NOS
PubChem CID
60835
Canonical SMILES
CNCCC(C1=CC=CS1)OC2=CC=CC3=CC=CC=C32
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
InChIKey
ZEUITGRIYCTCEM-KRWDZBQOSA-N
CAS Number
CAS 116539-59-4
ChEBI ID
CHEBI:36795
TTD Drug ID
D01AXB
DrugBank ID
DB00476
Combinatorial Therapeutic Effect(s) Validated Clinically or Experimentally
    α. A List of Natural Product(s) Able to Decrease the Adverse Effect of This Drug
          Phloretin      Prunus armeniaca     Click to Show/Hide the Molecular Data of This NP
                 Decreasing Adverse Drug Reaction     Click to Show/Hide
                    Representative Experiment Reporting the Effect of This Combination [2]
                    Detail(s)  Combination Info  click to show the detail info of this combination
                    In-vivo Model Diabetic neuropathy (DN) rat models were used in this study.
                    Experimental
                    Result(s)		 DX augmented the DM metabolic disturbance and hepatic dysfunction, however, PH effectively amended these disorders. The low-dose combination of both, had the merits of both medications, with the alleviation of their disadvantages.
Target and Pathway
Target(s) Norepinephrine transporter (NET)  Molecule Info  [3]
Serotonin transporter (SERT)  Molecule Info  [3]
KEGG Pathway Serotonergic synapse Click to Show/Hide
NetPath Pathway TCR Signaling Pathway Click to Show/Hide
Panther Pathway 5HT1 type receptor mediated signaling pathway Click to Show/Hide
2 5HT2 type receptor mediated signaling pathway
3 5HT3 type receptor mediated signaling pathway
4 5HT4 type receptor mediated signaling pathway
5 Adrenaline and noradrenaline biosynthesis
Reactome Na+/Cl- dependent neurotransmitter transporters Click to Show/Hide
WikiPathways Monoamine Transport Click to Show/Hide
2 SIDS Susceptibility Pathways
3 NRF2 pathway
4 Synaptic Vesicle Pathway
5 Serotonin Transporter Activity
6 Transport of glucose and other sugars, bile salts and organic acids, metal ions and amine compounds
References
Reference 1 URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 202).
Reference 2 Phloretin either alone or in combination with duloxetine alleviates the STZ-induced diabetic neuropathy in rats. Biomed Pharmacother. 2018 May;101:821-832.
Reference 3 Multi-target therapeutics: when the whole is greater than the sum of the parts. Drug Discov Today. 2007 Jan;12(1-2):34-42.
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