Tìm theo
Epoprostenol
Các tên gọi khác (10 ) :
  • (5Z,13e)-(15S)-6,9alpha-Epoxy-11alpha,15-dihydroxyprosta-5,13-dienoate
  • (5Z,9alpha,11alpha,13e,15S)-6,9-Epoxy-11,15-dihydroxyprosta-5,13-dien-1-oic acid
  • Epoprostenol
  • Flolan
  • PGI2
  • PGX
  • Prostacyclin
  • Prostaglandin I2
  • Prostaglandin x
  • Vasocyclin
platelet aggregation inhibitors, antihypertensive agents
Thuốc Gốc
Small Molecule
CAS: 35121-78-9
ATC: B01AC09
ĐG : GlaxoSmithKline Inc. , http://www.gsk.com
CTHH: C20H32O5
PTK: 352.4651
A prostaglandin that is a powerful vasodilator and inhibits platelet aggregation. It is biosynthesized enzymatically from prostaglandin endoperoxides in human vascular tissue. The sodium salt has been also used to treat primary pulmonary hypertension.
Nhận Dạng Quốc Tế & Đặc Tính Hóa Học
Công thức hóa học
C20H32O5
Phân tử khối
352.4651
Monoisotopic mass
352.224974134
InChI
InChI=1S/C20H32O5/c1-2-3-4-7-14(21)10-11-16-17-12-15(8-5-6-9-20(23)24)25-19(17)13-18(16)22/h8,10-11,14,16-19,21-22H,2-7,9,12-13H2,1H3,(H,23,24)/b11-10+,15-8-/t14-,16+,17+,18+,19-/m0/s1
InChI Key
InChIKey=KAQKFAOMNZTLHT-OZUDYXHBSA-N
IUPAC Name
5-[(3aR,4R,5R,6aS)-5-hydroxy-4-[(1E,3S)-3-hydroxyoct-1-en-1-yl]-hexahydro-2H-cyclopenta[b]furan-2-ylidene]pentanoic acid
Traditional IUPAC Name
5-[(3aR,4R,5R,6aS)-5-hydroxy-4-[(1E,3S)-3-hydroxyoct-1-en-1-yl]-hexahydrocyclopenta[b]furan-2-ylidene]pentanoic acid
SMILES
[H][C@]12C[C@@H](O)[C@H](\C=C\[C@@H](O)CCCCC)[C@@]1([H])CC(O2)=CCCCC(O)=O
Độ hòa tan
1.36e-01 g/l
logP
3
logS
-3.4
pKa (strongest acidic)
4.43
pKa (Strongest Basic)
-1.6
PSA
86.99 Å2
Refractivity
99.01 m3·mol-1
Polarizability
41.62 Å3
Rotatable Bond Count
10
H Bond Acceptor Count
5
H Bond Donor Count
3
Physiological Charge
-1
Number of Rings
2
Bioavailability
1
Rule of Five
true
Ghose Filter
true
Dược Lực Học : Epoprostenol has two major pharmacological actions: (1) direct vasodilation of pulmonary and systemic arterial vascular beds, and (2) inhibition of platelet aggregation. In animals, the vasodilatory effects reduce right and left ventricular afterload and increase cardiac output and stroke volume. The effect of epoprostenol on heart rate in animals varies with dose. At low doses, there is vagally mediated brudycardia, but at higher doses, epoprostenol causes reflex tachycardia in response to direct vasodilation and hypotension. No major effects on cardiac conduction have been observed. Additional pharmacologic effects of epoprostenol in animals include bronchodilation, inhibition of gastric acid secretion, and decreased gastric emptying. No available chemical assay is sufficiently sensitive and specific to assess the in vivo human pharmacokinetics of epoprostenol.
Cơ Chế Tác Dụng : A prostaglandin that is a powerful vasodilator and inhibits platelet aggregation. It is biosynthesized enzymatically from prostaglandin endoperoxides in human vascular tissue. The sodium salt has been also used to treat primary pulmonary hypertension. Prostaglandins are present in most body tissues and fluids and mediate many biological functions. Epoprostenol (PGI2) is a member of the family of prostaglandins that is derived from arachidonic acid. The major pharmacological actions of epoprostenol is ultimately inhibition of platelet aggregation. Prostacyclin (PGI2) is released by healthy endothelial cells and performs its function through a paracrine signaling cascade that involves G protein-coupled receptors on nearby platelets and endothelial cells. The platelet Gs protein-coupled receptor (prostacyclin receptor) is activated when it binds to PGI2. This activation, in turn, signals adenylyl cyclase to produce cAMP. cAMP goes on to inhibit any undue platelet activation (in order to promote circulation) and also counteracts any increase in cytosolic calcium levels which would result from thromboxane A2 (TXA2) binding (leading to platelet activation and subsequent coagulation). PGI2 also binds to endothelial prostacyclin receptors and in the same manner raise cAMP levels in the cytosol. This cAMP then goes on to activate protein kinase A (PKA). PKA then continues the cascade by phosphorylating and inhibiting myosin light-chain kinase which leads to smooth muscle relaxation and vasodilation. Notably, PGI2 and TXA2 work as physiological antagonists.
Dược Động Học :

▧ Volume of Distribution :
* 357 mL/kg
▧ Metabolism :
Epoprostenol is metabolized to 2 primary metabolites: 6-keto-PGF1α (formed by spontaneous degradation) and 6,15-diketo-13,14-dihydro-PGF1α (enzymatically formed), both of which have pharmacological activity orders of magnitude less than epoprostenol in animal test systems. Fourteen additional minor metabolites have been isolated from urine, indicating that epoprostenol is extensively metabolized in humans.
▧ Route of Elimination :
Epoprostenol is metabolized to 2 primary metabolites: 6-keto-PGF1α (formed by spontaneous degradation) and 6,15-diketo-13,14-dihydro-PGF1α (enzymatically formed), both of which have pharmacological activity orders of magnitude less than epoprostenol in animal test systems. Fourteen additional minor metabolites have been isolated from urine, indicating that epoprostenol is extensively metabolized in humans.
▧ Half Life :
The in vitro half-life of epoprostenol in human blood at 37°C and pH 7.4 is approximately 6 minutes; the in vivo half-life of epoprostenol in humans is therefore expected to be no greater than 6 minutes.
Độc Tính : Symptoms of overdose are extensions of its dose-limiting pharmacologic effects and include flushing, headache, hypotension, nausea, vomiting, and diarrhea. Most events were self-limiting and resolved with reduction or withholding of epoprostenol. Single intravenous doses at 10 and 50 mg/kg (2703 and 27,027 times the recommended acute phase human dose based on body surface area) were lethal to mice and rats, respectively. Symptoms of acute toxicity were hypoactivity, ataxia, loss of righting reflex, deep slow breathing, and hypothermia.
Chỉ Định : For the long-term intravenous treatment of primary pulmonary hypertension and pulmonary hypertension associated with the scleroderma spectrum of disease in NYHA Class III and Class IV patients who do not respond adequately to conventional therapy.
Tương Tác Thuốc :
  • Trandolapril The prostacyclin analogue, Epoprostenol, may increase the hypotensive effect of Trandolapril.
Liều Lượng & Cách Dùng : Injection, powder, for solution - Intravenous
Dữ Kiện Thương Mại
Giá thị trường
Nhà Sản Xuất
  • Công ty :
    Sản phẩm biệt dược : Flolan
Đóng gói
Tài Liệu Tham Khảo Thêm
drugbank
http://www.drugbank.ca/drugs/DB01240
PubChem Compound
http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=5282411
PubChem Substance
http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=46507362
KEGG Compound
http://www.genome.jp/dbget-bin/www_bget?cpd:C01312
KEGG Drug
http://www.genome.jp/dbget-bin/www_bget?drug:D00106
ChemSpider
http://www.chemspider.com/Chemical-Structure.4444093.html
National Drug Code Directory
http://www.hipaaspace.com/Medical_Billing/Coding/National.Drug.Codes/PDF/0173-0517-00
PharmGKB
http://www.pharmgkb.org/drug/PA449479
Wikipedia
http://en.wikipedia.org/wiki/Epoprostenol
RxList
http://www.rxlist.com/cgi/generic/flolan.htm
Drugs.com
http://www.drugs.com/cdi/epoprostenol.html
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