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| | Duloxetine Basic information |
| Product Name: | Duloxetine | | Synonyms: | methyl-[(3S)-3-(1-naphthyloxy)-3-(2-thienyl)propyl]amine;(3R)-N-methyl-3-(naphthalen-1-yloxy)-3-thiophen-2-ylpropan-1-amine;(S)-N-Methyl-3-(naphthalen-1-yloxy)-3-(thiophen-2-yl)propan-1-aMine;Duloxetine Hcl(S);Duloxetine, >=99%;Methyl[(3S)-3-(naphthalen-1-yloxy)-3-(thiophen-2-yl)propyl]aMine;DULOXETINE;N-Methyl-gama-(1-naphthalenyloxy)-2-thiophenepropanamine | | CAS: | 116539-59-4 | | MF: | C18H19NOS | | MW: | 297.41 | | EINECS: | 601-438-0 | | Product Categories: | API;ACTIVE PHARMACEUTICAL INGREDIENTS | | Mol File: | 116539-59-4.mol |  |
| | Duloxetine Chemical Properties |
| Boiling point | 466.2±40.0 °C(Predicted) | | density | 1.158±0.06 g/cm3(Predicted) | | storage temp. | Store at -20°C | | solubility | Soluble in DMSO | | pka | 10.02±0.10(Predicted) | | BCS Class | 2 | | InChI | InChI=1/C18H19NOS.ClH/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;1H/t17-;/s3 | | InChIKey | BFFSMCNJSOPUAY-VOPAOICTNA-N | | SMILES | C1(=CC=CS1)[C@H](CCNC)OC1=CC=CC2=CC=CC=C12.Cl |&1:5,r| | | EPA Substance Registry System | 2-Thiophenepropanamine, N-methyl-?-(1-naphthalenyloxy)-, (?S)- (116539-59-4) |
| | Duloxetine Usage And Synthesis |
| Uses | Antidepressant. | | Definition | ChEBI: (S)-duloxetine is a duloxetine. It is an enantiomer of a (R)-duloxetine. | | Brand name | Cymbalta (Lilly). | | General Description | Duloxetine (Cymbalta) is a newer antidepressant. It islargely like venlafaxine, which is an SNERI (selective norepinephrinereuptake inhibitor). | | Pharmacokinetics | Duloxetine appears to be fairly well absorbed after oral doses, with peak plasma levels in 6 to 10 hours and
linear pharmacokinetics. The drug is extensively metabolized in the liver to active
metabolites, with 72% of an oral dose primarily excreted in the urine as conjugated metabolites and up to
15% appearing in the feces.
N-demethylation to an active metabolite (CYP2D6) and hydroxylation of the naphthyl ring (CYP1A2) at either
the 4-, 5-, or 6-positions are the main metabolic pathways for duloxetine. Its metabolites are primarily
excreted into the urine as glucuronide, sulfate, and O-methylated conjugation products. The
major metabolites found in plasma also were found in the urine. Preclinical data for 4-hydroxyduloxetine
suggests it has a similar pharmacological profile to duloxetine, with selective inhibition of SERT but less
activity at the NET. | | Clinical Use | Duloxetine has been approved for the treatment of depression and diabetic peripheral
neuropathic pain. It is another analogue in the line of fluoxetine-based products from Lilly, in which the phenyl and phenoxy groups of fluoxetine have been respectively replaced with the benzene isostere,
thiophene, and a
naphthyloxy group (previously described under fluoxetine). Duloxetine exhibits dual inhibition with high
affinity for the SERTs and NETs, with a five times preferential inhibition of the SERT. Duloxetine
appears to be a more potent in vitro blocker of SERTs and NETs than venlafaxine. In humans, duloxetine has
a low affinity for the other neuroreceptors, suggesting low incidence of unwanted adverse effects. | | Drug interactions | Potentially hazardous interactions with other drugs
Antibacterials: metabolism inhibited by ciprofloxacin
- avoid.
Anticoagulants: possibly increased risk of bleeding
with dabigatran.
Other CNS medication: enhanced effect.
Antidepressants: avoid with MAOIs, moclobemide,
St John’s wort, tryptophan, venlaflaxine, amitriptyline,
clomipramine and SSRIs due to increased risk of
serotonin syndrome; increased risk of side effects
with tricyclic antidepressants; fluvoxamine decreases
the clearance of duloxetine by 77% - avoid; possible
increased risk of convulsions with vortioxetine.
Antimalarials: avoid with artemether/lumefantrine
and piperaquine with artenimol.
Dapoxetine: avoid concomitant use.
Methylthioninium: risk of CNS toxicity - avoid if
possible. | | Metabolism | Duloxetine is extensively metabolised and the metabolites
are excreted principally in urine. Both cytochromes
P450-2D6 and 1A2 catalyse the formation of the two major
metabolites, glucuronide conjugate of 4-hydroxy duloxetine
and sulphate conjugate of 5-hydroxy, 6-methoxy duloxetine.
Based upon in vitro studies, the circulating metabolites of
duloxetine are considered pharmacologically inactive |
| | Duloxetine Preparation Products And Raw materials |
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