Tìm theo
Levomilnacipran
Các tên gọi khác (2) :
  • F-2695
  • Levomilnacipran
serotonin uptake inhibitors
Thuốc Gốc
Small Molecule
CAS: 96847-55-1
CTHH: C15H22N2O
PTK: 246.348
Levomilnacipran is a selective serotonin and norepinephrine reuptake inhibitor. Chemically, levomilnacipran is the 1S,2R-enantiomer of milnacipran. FDA approved on July 25, 2013.
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+/m0/s1
InChI Key
InChIKey=GJJFMKBJSRMPLA-DZGCQCFKSA-N
IUPAC Name
(1S,2R)-2-(aminomethyl)-N,N-diethyl-1-phenylcyclopropane-1-carboxamide
Traditional IUPAC Name
levomilnacipran
SMILES
CCN(CC)C(=O)[C@]1(C[C@H]1CN)C1=CC=CC=C1
logP
1.42
pKa (Strongest Basic)
9.83
PSA
46.33 Å2
Refractivity
73.81 m3·mol-1
Polarizability
28.33 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 : Levomilnacipran binds with high affinity to human serotonin (5-HT) and norepinephrine (NE) transporters (Ki = 11 and 91 nM, respectively). It potently inhibits 5-HT and NE reuptake (IC50 = 16 - 19 and 11 nM, respectively). Levomilnacipran does not bind to any other receptors, ion channels, or transporters, including serotonergic (5HT1-7), α- and β adrenergic, muscarinic, or histaminergic receptors and Ca2+, Na+, K+ or Cl- channels to a significant degree. Levomilnacipran did not inhibit monoamine oxidase (MAO). Furthermore, levomilnacipran does not prolong the QTc interval to a clinically relevant extent.
Cơ Chế Tác Dụng : Levomilnacipran is a selective serotonin and norepinephrine reuptake inhibitor. Chemically, levomilnacipran is the 1S,2R-enantiomer of milnacipran. FDA approved on July 25, 2013. The exact mechanism of the antidepressant action of levomilnacipran is unknown but is thought to be related to the potentiation of serotonin and norephinephrine in the central nervous system through inhibition of reuptake at serotonin and norepinephrine transporters.
Dược Động Học :
▧ Absorption :
The relative bioavailability after administration of the extended-release capsule was 92% when compared to oral solution. Food does not affect the concentration of levomilnacipran. After daily dosing of levomilnacipran (extended-release capsule) the mean Cmax is 341 ng/mL, and the mean steady-state AUC value is 5196 ng·h/mL. The Tmax is 6 - 8 hours after oral administration. Interconversion of stereoisomers does not occur in humans.
▧ Volume of Distribution :
* 387 - 473 L [apparent volume of distribution]
▧ Protein binding :
22% bound to human plasma protein over concentration range of 10 to 1000 ng/mL.
▧ Metabolism :
Hepatic. Levomilnacipran undergoes desethylation to form desethyl levomilnacipran and hydroxylation to form p-hydroxy-levomilnacipran. Desethylation is facilitated primarily by CYP3A4 and by CYP2C8, 2C19, 2D6, and 2J2 to a lesser extent. Both metabolites undergo further conjugation with glucuronide to form conjugates.
▧ Route of Elimination :
Levomilnacipran and its metabolites are eliminated primarily by renal excretion. 58% of the dose is excreted in urine as unchanged levomilnacipran. N-desethyl levomilnacipran is the major metabolite excreted in the urine and accounted for approximately 18% of the dose. Other identifiable metabolites excreted in the urine are levomilnacipran glucuronide (4%), desethyl-levomilnacipran glucuronide (3%), p-hydroxy levomilnacipran glucuronide (1%), and p-hydroxylevomilnacipran (1%). The metabolites are inactive.
▧ Half Life :
12 hours
▧ Clearance :
* 21 - 29 L/h [mean apparent total clearance]
Độc Tính : The most common adverse reactions are nausea, constipation, hyperhidrosis, heart rate increase, erectile dysfunction, tachycardia, vomiting, and palpitations.
Chỉ Định : Levomilnacipran is a serotonin and norepinephrine reuptake inhibitor and is indicated for the treatment of major depressive disorder (MDD).
Tương Tác Thuốc :
  • Ketoconazole Strong CYP3A4 inhibitors may increase exposure levomilnacipran.
Liều Lượng & Cách Dùng : Capsule, extended release - Oral - 20 mg, 40 mg, 80 mg, 120 mg
Dữ Kiện Thương Mại
Nhà Sản Xuất
  • Công ty : Forest Labs
    Sản phẩm biệt dược : Fetzima
Tài Liệu Tham Khảo Thêm
drugbank
http://www.drugbank.ca/drugs/DB08918
KEGG Drug
http://www.genome.jp/dbget-bin/www_bget?drug:D10072
Wikipedia
http://en.wikipedia.org/wiki/Levomilnacipran
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