Tìm theo
Milnacipran
Các tên gọi khác (4 ) :
  • (-)-milnacipran
  • Midalcipran
  • Milnacipran
  • Milnacipranum
serotonin uptake inhibitors, adrenergic uptake inhibitors, antidepressive agents
Thuốc Gốc
Small Molecule
CAS: 92623-85-3
ATC: N06AX17
ĐG : Forest Laboratories Inc. , http://www.frx.com
CTHH: C15H22N2O
PTK: 246.348
Milnacipran is an antidepressant of the serotonin-norepinephrine reuptake inhibitor class. It more potently inhibits norepinephrine uptake than serotonin. It is provided as a racemic mixture. FDA approved in January 2009.
Nhận Dạng Quốc Tế & Đặc Tính Hóa Học
Công thức hóa học
C15H22N2O
Phân tử khối
246.348
Monoisotopic mass
246.173213336
InChI
InChI=1S/C15H22N2O/c1-3-17(4-2)14(18)15(10-13(15)11-16)12-8-6-5-7-9-12/h5-9,13H,3-4,10-11,16H2,1-2H3/t13-,15+/m1/s1
InChI Key
InChIKey=GJJFMKBJSRMPLA-HIFRSBDPSA-N
IUPAC Name
(1R,2S)-2-(aminomethyl)-N,N-diethyl-1-phenylcyclopropane-1-carboxamide
Traditional IUPAC Name
milnacipran
SMILES
CCN(CC)C(=O)[C@@]1(C[C@@H]1CN)C1=CC=CC=C1
Độ tan chảy
179°C
Độ hòa tan
19 mg/mL
logP
1.42
logS
-2.3
pKa (Strongest Basic)
9.83
PSA
46.33 Å2
Refractivity
73.81 m3·mol-1
Polarizability
28.03 Å3
Rotatable Bond Count
5
H Bond Acceptor Count
2
H Bond Donor Count
1
Physiological Charge
1
Number of Rings
2
Bioavailability
1
Rule of Five
true
Ghose Filter
true
Dược Lực Học : Although milnacipran prolongs the QTc interval, the increase is not considered clinically significant.
Cơ Chế Tác Dụng : Milnacipran is an antidepressant of the serotonin-norepinephrine reuptake inhibitor class. It more potently inhibits norepinephrine uptake than serotonin. It is provided as a racemic mixture. FDA approved in January 2009. Milnacipran inhibits norepinephrine and serotonin reuptake in a 3:1 ratio, in practical use this means a balanced (equal) action upon both transmitters. The serotonin reuptake inhibition is likely to improve depression, while the norepinephrine reuptake inihibition probably improves chronic pain. Milnacipran exerts no significant actions on postynaptic H1, alpha-1, D1, D2, and muscarinic receptors, as well as on benzodiazepine/opiate binding sites. [Wikipedia]
Dược Động Học :
▧ Absorption :
Milnacipran is well absorbed following oral administration with an absolute bioavailability of 85-90%. Meals have no effect on absorption. Peak concentrations occur 2 -4 hours post-administration and is delayed in elderly patients. Time to steady state = 36 - 48 hours;
▧ Volume of Distribution :
400 L, following a single IV dose to a healthy subject.
▧ Protein binding :
Plasma protein binding is 13%.
▧ Metabolism :
Hepatic metabolism of milnacipran occurs via glucuronidation. No involvement of CYP450 isozymes or active metabolites found.
▧ Route of Elimination :
It is excreted predominantly unchanged in urine (50%- 60%, 24% as l-milnacipran and 31% as d-milnacipran). The l-milnacipran carbamoyl-O-glucuronide was the major metabolite excreted in urine and accounted for approximately 17% of the dose; approximately 2% of the dose was excreted in urine as d-milnacipran carbamoyl-O-glucuronide. Approximately 8% of the dose was excreted in urine as the N-desethyl milnacipran metabolite.
▧ Half Life :
The terminal elimination half-life, when given to healthy subjects is 6-8 hours. When given to severe renal impairment patients is 7 - 10 hours. The active enantiomer, d-milnacipran, has a longer elimination half-life (8-10 hours) than the l-enantiomer (4-6 hours).
Độc Tính : LD50, oral, rat: 213 mg/kg. The most frequently occurring adverse reactions (≥ 5% and greater than placebo) were nausea, headache, constipation, dizziness, insomnia, hot flush, hyperhidrosis, vomiting, palpitations, heart rate increased, dry mouth, and hypertension.
Chỉ Định : Milnacipran is used to treat moderate to severe clinical depression but this indication is not yet FDA-approved in the USA. Milnacipran is labelled for the treatment of fibromyalgia pain.
Tương Tác Thuốc :
  • Clonidine Because Savella inhibits norepinephrine reuptake, co-administration with clonidine may inhibit clonidine's anti-hypertensive effect.
  • Desvenlafaxine Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
  • Digoxin Use of Savella concomitantly with digoxin may be associated with potentiation of adverse hemodynamic effects. Co-administration of Savella and intravenous digoxin should be avoided.
  • Furazolidone Increase serotonin levels. Combination therapy is contraindicated.
  • Iobenguane Milnacipran decreases the effects of Iobenguane thus increases the risk of producing a false-negative result. May discontinue milnacipran for at least 5 half-live.
  • Isocarboxazid Increase serotonin levels. Combination therapy is contraindicated.
  • Moclobemide Increase serotonin levels. Combination therapy is contraindicated.
  • Pargyline Increase serotonin levels. Combination therapy is contraindicated.
  • Phenelzine Increase serotonin levels. Combination therapy is contraindicated.
  • Procarbazine Increase serotonin levels. Combination therapy is contraindicated.
  • Rasagiline Increase serotonin levels. Combination therapy is contraindicated.
  • 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.
  • Venlafaxine Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
  • Zolmitriptan Use of two serotonin modulators, such as zolmitriptan and milnacipran, increases the risk of serotonin syndrome. Consider alternate therapy or monitor for serotonin syndrome during concomitant therapy.
Liều Lượng & Cách Dùng : Tablet - Oral - 12.5 mg, 25 mg, 50 mg, 100 mg
Dữ Kiện Thương Mại
Giá thị trường
  • Biệt dược thương mại : Savella 100 mg tablet
    Giá bán buôn : USD >2.13
    Đơn vị tính : tablet
  • Biệt dược thương mại : Savella 12.5 mg tablet
    Giá bán buôn : USD >2.13
    Đơn vị tính : tablet
  • Biệt dược thương mại : Savella 25 mg tablet
    Giá bán buôn : USD >2.13
    Đơn vị tính : tablet
  • Biệt dược thương mại : Savella 50 mg tablet
    Giá bán buôn : USD >2.13
    Đơn vị tính : tablet
Nhà Sản Xuất
  • Công ty :
    Sản phẩm biệt dược : Dalcipran
  • Công ty :
    Sản phẩm biệt dược : Ixel
  • Sản phẩm biệt dược : Savella
  • Công ty :
    Sản phẩm biệt dược : Toledomin
Đóng gói
Tài Liệu Tham Khảo Thêm
drugbank
http://www.drugbank.ca/drugs/DB04896
PubChem Compound
http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=65833
PubChem Substance
http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=46506141
KEGG Drug
http://www.genome.jp/dbget-bin/www_bget?drug:D08222
ChemSpider
http://www.chemspider.com/Chemical-Structure.59245.html
BindingDB
http://www.bindingdb.org/bind/chemsearch/marvin/MolStructure.jsp?monomerid=50239538
National Drug Code Directory
http://www.hipaaspace.com/Medical_Billing/Coding/National.Drug.Codes/PDF/0456-1512-60
PharmGKB
http://www.pharmgkb.org/drug/PA164752812
Wikipedia
http://en.wikipedia.org/wiki/Milnacipran
RxList
http://www.rxlist.com/savella-drug.htm
Drugs.com
http://www.drugs.com/cdi/milnacipran.html
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