Tìm theo
Duloxetine
Các tên gọi khác (2) :
  • (3S)-N-Methyl-3-(1-naphthyloxy)-3-(2-thienyl)propan-1-amine
  • LY 248686
Thuốc Gốc
Small Molecule
CAS: 136434-34-9
ATC: N06AX21
ĐG : Bryant Ranch Prepack , http://bryantranchprepack.com
CTHH: C18H19NOS
PTK: 297.415
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.
Nhận Dạng Quốc Tế & Đặc Tính Hóa Học
Công thức hóa học
C18H19NOS
Phân tử khối
297.415
Monoisotopic mass
297.118734925
InChI
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
InChI Key
InChIKey=ZEUITGRIYCTCEM-KRWDZBQOSA-N
IUPAC Name
methyl[(3S)-3-(naphthalen-1-yloxy)-3-(thiophen-2-yl)propyl]amine
Traditional IUPAC Name
duloxetine
SMILES
CNCC[C@H](OC1=CC=CC2=CC=CC=C12)C1=CC=CS1
Độ hòa tan
2.96e-03 g/l
logP
4
logS
-5
pKa (Strongest Basic)
9.7
PSA
21.26 Å2
Refractivity
87.73 m3·mol-1
Polarizability
33.15 Å3
Rotatable Bond Count
6
H Bond Acceptor Count
2
H Bond Donor Count
1
Physiological Charge
1
Number of Rings
3
Bioavailability
1
Rule of Five
true
Ghose Filter
true
MDDR-Like Rule
true
Dược Lực Học : Duloxetine is in a class of medications called selective serotonin and norepinephrine reuptake inhibitors (SSNRIs) and primarily targets major depressive disorders (MDD) and stress urinary incontinence (SUI). Duloxetine is also used to treat pain and tingling caused by diabetic neuropathy (damage to nerves that can develop in people who have diabetes). Known also as LY248686, it is a potent dual inhibitor of serotonin (5-hydroxytryptamine, 5-HT) and norepinephrine (NE) reuptake, possessing comparable affinities in binding to NE and 5-HT transport sites. Interestingly, its behavior contrasts to most other dual-reuptake inhibitors. Furthermore, duloxentine lacks affinity for monoamine receptors within the central nervous system.
Cơ Chế Tác Dụng : 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. 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.
Dược Động Học :
▧ Absorption :
Orally administered duloxetine hydrochloride is well absorbed.
▧ Volume of Distribution :
* 1640 L
▧ Protein binding :
Protein binding is greater than 90%.
▧ Metabolism :
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)
Độc Tính : Oral, rat LD50: 491 mg/kg for males and 279 mg/kg for females. Symptoms of overdose include tremors, convulsions, reduced activity, slow pupillary response, intermittent tremors, and rigidity.
Chỉ Định : 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.
Tương Tác Thuốc :
  • Aldesleukin Monitor therapy due to enhanced orthostatic hypotensive effect of duloxetine.
  • Aliskiren Monitor therapy due to enhanced orthostatic hypotensive effect of duloxetine.
  • Amitriptyline Possible increase in the levels of this agent when used with duloxetine
  • Ciprofloxacin Ciprofloxacin, a strong CYP1A2 inhibitor, may decrease the metabolism of duloxetine. Monitor for changes in the therapeutic and adverse effects of duloxetine if ciprofloxacin is initiated or discontinued.
  • Desipramine Possible increase in the levels of this agent when used with duloxetine
  • Desvenlafaxine Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
  • Flecainide Possible increase in the levels of this agent when used with duloxetine
  • Fluvoxamine Fluvoxamine increases the effect and toxicity of duloxetine
  • Imipramine Possible increase in the levels of this agent when used with duloxetine
  • Isocarboxazid Possible severe adverse reaction with this combination
  • Nortriptyline Possible increase in the levels of this agent when used with duloxetine
  • Phenelzine Possible severe adverse reaction with this combination
  • Propafenone Possible increase in the levels of this agent when used with duloxetine
  • Rasagiline Possible severe adverse reaction with this combination
  • Tamoxifen Duloxetine may decrease the therapeutic effect of Tamoxifen by decreasing the production of active metabolites. Consider alternate therapy.
  • Tamsulosin Duloxetine, a CYP2D6 inhibitor, may decrease the metabolism and clearance of Tamsulosin, a CYP2D6 substrate. Monitor for changes in therapeutic/adverse effects of Tamsulosin if Duloxetine is initiated, discontinued, or dose changed.
  • Terbinafine Terbinafine may reduce the metabolism and clearance of Duloxetine. Consider alternate therapy or monitor for therapeutic/adverse effects of Duloxetine if Terbinafine is initiated, discontinued or dose changed.
  • Thiabendazole The strong CYP1A2 inhibitor, Thiabendazole, may increase the effects and toxicity of Duloxetine by decreasing Duloxetine metabolism and clearance. Monitor for changes in the therapeutic and adverse effects of Duloxetine if Thiabendazole is initiated, discontinued or dose changed.
  • Thioridazine Increased risk of cardiotoxicity and arrhythmias
  • Tramadol Duloxetine may decrease the effect of Tramadol by decreasing active metabolite production. Increased risk of serotonin syndrome. Monitor for Tramadol efficacy and symptoms of serotonin syndrome.
  • Tranylcypromine Increased risk of serotonin syndrome. Concomitant therapy should be avoided. A significant washout period, dependent on the half-lives of the agents, should be employed between therapies.
  • Trazodone Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
  • Trimipramine Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
  • Triprolidine The CNS depressants, Triprolidine and Duloxetine, may increase adverse/toxic effects due to additivity. Monitor for increased CNS depressant effects during concomitant therapy.
  • Venlafaxine Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
  • Zolmitriptan Use of two serotonin modulators, such as zolmitriptan and duloxetine, increases the risk of serotonin syndrome. Consider alternate therapy or monitor for serotonin syndrome during concomitant therapy.
Liều Lượng & Cách Dùng : Capsule, coated pellets - Oral
Dữ Kiện Thương Mại
Giá thị trường
Nhà Sản Xuất
  • Công ty :
    Sản phẩm biệt dược : Ariclaim
  • Công ty :
    Sản phẩm biệt dược : Cymbalta
  • Công ty :
    Sản phẩm biệt dược : Dulane
  • Công ty :
    Sản phẩm biệt dược : Duzela
  • Công ty :
    Sản phẩm biệt dược : Xeristar
  • Công ty :
    Sản phẩm biệt dược : Yentreve
Đóng gói
Tài Liệu Tham Khảo Thêm
drugbank
http://www.drugbank.ca/drugs/DB00476
PubChem Compound
http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=60835
PubChem Substance
http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=46507937
KEGG Drug
http://www.genome.jp/dbget-bin/www_bget?drug:D01179
ChemSpider
http://www.chemspider.com/Chemical-Structure.54822.html
National Drug Code Directory
http://www.hipaaspace.com/Medical_Billing/Coding/National.Drug.Codes/PDF/54868-5215-2
PharmGKB
http://www.pharmgkb.org/drug/PA10066
Wikipedia
http://en.wikipedia.org/wiki/Duloxetine
RxList
http://www.rxlist.com/cgi/generic/cymbalta.htm
Drugs.com
http://www.drugs.com/cdi/duloxetine-delayed-release-capsules.html
... loading
... loading