116539-59-4 Usage
Uses
Antidepressant.
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 drugsAntibacterials: 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
Check Digit Verification of cas no
The CAS Registry Mumber 116539-59-4 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 1,1,6,5,3 and 9 respectively; the second part has 2 digits, 5 and 9 respectively.
Calculate Digit Verification of CAS Registry Number 116539-59:
(8*1)+(7*1)+(6*6)+(5*5)+(4*3)+(3*9)+(2*5)+(1*9)=134
134 % 10 = 4
So 116539-59-4 is a valid CAS Registry Number.
InChI:InChI=1/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-/m1/s1
116539-59-4Relevant articles and documents
Preparation method of duloxetine
-
, (2021/09/26)
To the method, 1 - naphthol and 3 - (2 - thienyl) -2 - acrolein serve as starting materials, and (S)-3 - (1 - naphthyloxy) -3 - (2 - thienyl) propanal is obtained through addition reaction under the action of a catalyst. The raw materials are cheap and easily available, and 1 - fluoronaphthalene which is expensive is not needed. Sodium hydride and operation are tedious, the cost is low, the process operation is safe and convenient, the three wastes are small in generation amount, and green and environment-friendly. The reaction atom economy is high, the reaction selectivity of each step is high, the side reaction is small, the optical purity and yield of the target product are high, and the green industrial production is facilitated.
Duloxetine hydrochloride salt of basic and duloxetine (by machine translation)
-
Paragraph 0052-0054, (2017/06/02)
[Problem] to suppress toxic byproducts, and suppressing the formation of decomposition products of high purity optical isomers as well as the method for manufacturing a basic duloxetine hydrochloride duloxetine. [Solution] a basic manufacturing method of duloxetine, [...], potassium hydroxide and toluene in the presence of alcohol in the mixing step, and, by heating the reaction mixture obtained, comprising the step of distilling off the solvent in the reaction portion, a basic manufacturing method of duloxetine. [Drawing] no (by machine translation)
Method for the synthesis of duloxetine
-
, (2016/10/07)
A synthetic method of duloxetine is as below: reacting water, tetrahydrofuran or dioxane, 1-chloro ethyl-N-methyl-((S)-3-(naphthalene-1-phenoxy)-3-(thiophene-2-yl) propyl) carbamate and alkali at a reflux temperature of 20 DEG C, preferably 50 DEG C; after the reaction, condensing a reaction liquid; and adding another organic solvent for extraction, so as to obtain a solution containing dutoxetine. Compared with the existing method for preparing duloxetine, the method overcomes the disadvantages of long reaction time or high reaction temperature, high energy consumption, long production cycle, low yield, a large amount of industrial waste water difficult to process, harm to the environment, flammable and explosive reagents and huge security hidden trouble, and has the advantages of low reaction temperature, short reaction time, a small amount of produced industrial waste liquid, greenness, environment-friendliness, high safety, and suitability for large-scale industrial production of duloxetine.
