2847 Duloxetine Duloxetine (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. 136434-34-9 60835 C18H19NOS 297.118740 White powder. 2.96e-03 g/L Orally administered duloxetine hydrochloride is well absorbed. Duloxetine 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. The 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) Oral, rat LD₅₀: 491 mg/kg for males and 279 mg/kg for females (A308). No indication of carcinogenicity to humans (not listed by IARC). For 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. Symptoms of overdose include tremors, convulsions, reduced activity, slow pupillary response, intermittent tremors, and rigidity. There 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. (L1712) 2009-07-21T20:27:00Z 2026-05-14T16:39:58Z Duloxetine 36795 Duloxetine DB00476 true CNCC[C@H](OC1=CC=CC2=CC=CC=C12)C1=CC=CS1 C18H19NOS 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 ZEUITGRIYCTCEM-KRWDZBQOSA-N 297.415 297.118734925 Exogenous Solid 4 HMDB14619 CHEMBL1175 54822 <p>Richard A. Berglund, &#8220;Intermediate useful for the asymmetric synthesis of duloxetine.&#8221; U.S. Patent US5491243, issued June, 1991.</p> CHEM002207 DTXSID6048385 NS00008615 methyl[(3S)-3-(naphthalen-1-yloxy)-3-(thiophen-2-yl)propyl]amine 21.259999999999998 87.73390000000003 33.15278651399598 6 2 1 9.702576554982972 1 3 4.72 -5.00 2.96e-03 g/l