Tìm theo
Mibefradil
Thuốc Gốc
Small Molecule
CAS: 116644-53-2
ATC: C08CX01
CTHH: C29H38FN3O3
PTK: 495.6287
Mibefradil was withdrawn from the market in 1998 because of potentially harmful interactions with other drugs.
Nhận Dạng Quốc Tế & Đặc Tính Hóa Học
Công thức hóa học
C29H38FN3O3
Phân tử khối
495.6287
Monoisotopic mass
495.289720302
InChI
InChI=1S/C29H38FN3O3/c1-20(2)28-23-12-11-22(30)18-21(23)13-14-29(28,36-27(34)19-35-4)15-17-33(3)16-7-10-26-31-24-8-5-6-9-25(24)32-26/h5-6,8-9,11-12,18,20,28H,7,10,13-17,19H2,1-4H3,(H,31,32)/t28-,29-/m0/s1
InChI Key
InChIKey=HBNPJJILLOYFJU-VMPREFPWSA-N
IUPAC Name
(1S,2S)-2-(2-{[3-(1H-1,3-benzodiazol-2-yl)propyl](methyl)amino}ethyl)-6-fluoro-1-(propan-2-yl)-1,2,3,4-tetrahydronaphthalen-2-yl 2-methoxyacetate
Traditional IUPAC Name
mibefradil
SMILES
COCC(=O)O[C@]1(CCN(C)CCCC2=NC3=CC=CC=C3N2)CCC2=C(C=CC(F)=C2)[C@@H]1C(C)C
Độ hòa tan
1.04e-03 g/l
logP
5.16
logS
-5.7
pKa (strongest acidic)
12.54
pKa (Strongest Basic)
9.82
PSA
67.45 Å2
Refractivity
139.73 m3·mol-1
Rotatable Bond Count
12
H Bond Acceptor Count
4
H Bond Donor Count
1
Physiological Charge
1
Number of Rings
4
Bioavailability
0
MDDR-Like Rule
true
caco2 Permeability
-4.87
Dược Lực Học : Mibefradil belongs to a group of medicines called calcium channel blocking agents, or, more commonly, calcium channel blockers. Calcium channel blocking agents affect the movement of calcium into the cells of the heart and blood vessels. As a result, they relax blood vessels and increase the supply of blood and oxygen to the heart while reducing its workload. Mibefradil is a benzimidazoyl-substituted tetraline that selectively binds and inhibits T-type calcium channels.
Cơ Chế Tác Dụng : Mibefradil was withdrawn from the market in 1998 because of potentially harmful interactions with other drugs. Mibefradil is a tetralol calcium channel blocking agent that inhibits the influx of calcium ions across both the T (low-voltage) and L (high-voltage) calcium channels of cardiac and vascular smooth muscle, with a greater selectivity for T channels. Vasodilation occurs in vascular smooth muscle, causing a decrease in peripheral vascular resistance and a resulting decrease in blood pressure. Mibefradil causes a slight increase in cardiac output during chronic dosing. Mibefradil slows sinus and atrioventricular (AV) node conduction, producing a slight reduction in heart rate and a slight increase in the PR interval. It has also been shown to slightly lengthen the corrected sinus node recovery time and AH interval and to raise the Wenckebach point. The mechanism by which mibefradil reduces angina is not known, but is thought to be attributed to a reduction in heart rate, total peripheral resistance (afterload), and the heart rate–systolic blood pressure product at any given level of exercise. The result of these effects is a decrease in cardiac workload and myocardial oxygen demand.
Dược Động Học :
▧ Absorption :
Bioavailability after a single dose is 70%. After multiple dosing, the proportion of mibefradil undergoing first-pass metabolism is reduced, resulting in a steady state bioavailability of approximately 90%. Food does not affect the rate or extent of absorption of mibefradil.
▧ Protein binding :
≥ 99%, primarily to alpha 1-acid glycoprotein.
▧ Metabolism :
The two metabolic pathways that mibefradil undergoes are esterase-catalyzed hydrolysis of the ester side chain (producing an alcohol metabolite) and cytochrome P450 3A4-catalyzed oxidation (that becomes less important during chronic dosing). The pharmacologic effect of the metabolite is approximately 10% of that of the parent mibefradil.
▧ Half Life :
17 to 25 hours at steady state.
Chỉ Định : For the treatment of angina and high blood pressure.
Tương Tác Thuốc :
  • Astemizole Increased risk of cardiotoxicity and arrhythmias
  • Atomoxetine The CYP2D6 inhibitor could increase the effect and toxicity of atomoxetine
  • Cisapride Mibefradil increases levels of cisapride
  • Tacrolimus The calcium channel blocker, Mibefradil, may increase the blood concentration of Tacrolimus. Monitor for changes in the therapeutic/toxic effects of Tacrolimus if Mibefradil therapy is initiated, discontinued or altered.
  • Terfenadine Increased risk of cardiotoxicity and arrhythmias
Dữ Kiện Thương Mại
Nhà Sản Xuất
  • Công ty :
    Sản phẩm biệt dược : Posicor
Tài Liệu Tham Khảo Thêm
drugbank
http://www.drugbank.ca/drugs/DB01388
PubChem Compound
http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=60663
PubChem Substance
http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=46504498
KEGG Compound
http://www.genome.jp/dbget-bin/www_bget?cpd:C07222
ChemSpider
http://www.chemspider.com/Chemical-Structure.54673.html
BindingDB
http://www.bindingdb.org/bind/chemsearch/marvin/MolStructure.jsp?monomerid=50117922
PharmGKB
http://www.pharmgkb.org/drug/PA450492
Wikipedia
http://en.wikipedia.org/wiki/Mibefradil
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