Tìm theo
Isradipine
Các tên gọi khác (3) :
  • Dynacirc
  • Isradipino
  • Isradipinum
antihypertensive agents, vasodilator agents, calcium channel blockers
Thuốc Gốc
Small Molecule
CAS: 75695-93-1
ATC: C08CA03
ĐG : Actavis Group , http://www.actavis.com
CTHH: C19H21N3O5
PTK: 371.3871
Isradipine belongs to the dihydropyridine (DHP) class of calcium channel blockers (CCBs), the most widely used class of CCBs. It is structurally related to felodipine, nifedipine, and nimodipine and is the most potent calcium-channel blocking agent of the DHP class. Isradipine binds to calcium channels with high affinity and specificity and inhibits calcium flux into cardiac and arterial smooth muscle cells. It exhibits greater selectivity towards arterial smooth muscle cells owing to alternative splicing of the alpha-1 subunit of the channel and increased prevalence of inactive channels in smooth muscle cells. Isradipine may be used to treat mild to moderate essential hypertension.
Nhận Dạng Quốc Tế & Đặc Tính Hóa Học
Công thức hóa học
C19H21N3O5
Phân tử khối
371.3871
Monoisotopic mass
371.148120797
InChI
InChI=1S/C19H21N3O5/c1-9(2)26-19(24)15-11(4)20-10(3)14(18(23)25-5)16(15)12-7-6-8-13-17(12)22-27-21-13/h6-9,16,20H,1-5H3
InChI Key
InChIKey=HMJIYCCIJYRONP-UHFFFAOYSA-N
IUPAC Name
3-methyl 5-propan-2-yl 4-(2,1,3-benzoxadiazol-4-yl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate
Traditional IUPAC Name
isradipine
SMILES
COC(=O)C1=C(C)NC(C)=C(C1C1=CC=CC2=NON=C12)C(=O)OC(C)C
Độ tan chảy
168-170 °C
Độ hòa tan
Practically insoluble (< 10 mg/L at 37 °C)
logP
4.28
logS
-3.2
pKa (Strongest Basic)
5.33
PSA
103.55 Å2
Refractivity
100.08 m3·mol-1
Polarizability
37.39 Å3
Rotatable Bond Count
6
H Bond Acceptor Count
5
H Bond Donor Count
1
Physiological Charge
0
Number of Rings
3
Bioavailability
1
Rule of Five
true
Ghose Filter
true
MDDR-Like Rule
true
Dược Lực Học : Isradipine decreases arterial smooth muscle contractility and subsequent vasoconstriction by inhibiting the influx of calcium ions through L-type calcium channels. Calcium ions entering the cell through these channels bind to calmodulin. Calcium-bound calmodulin then binds to and activates myosin light chain kinase (MLCK). Activated MLCK catalyzes the phosphorylation of the regulatory light chain subunit of myosin, a key step in muscle contraction. Signal amplification is achieved by calcium-induced calcium release from the sarcoplasmic reticulum through ryanodine receptors. Inhibition of the initial influx of calcium decreases the contractile activity of arterial smooth muscle cells and results in vasodilation. The vasodilatory effects of isradipine result in an overall decrease in blood pressure.
Cơ Chế Tác Dụng : Isradipine belongs to the dihydropyridine (DHP) class of calcium channel blockers (CCBs), the most widely used class of CCBs. It is structurally related to felodipine, nifedipine, and nimodipine and is the most potent calcium-channel blocking agent of the DHP class. Isradipine binds to calcium channels with high affinity and specificity and inhibits calcium flux into cardiac and arterial smooth muscle cells. It exhibits greater selectivity towards arterial smooth muscle cells owing to alternative splicing of the alpha-1 subunit of the channel and increased prevalence of inactive channels in smooth muscle cells. Isradipine may be used to treat mild to moderate essential hypertension. Isradipine belongs to the dihydropyridine (DHP) class of calcium channel blockers (CCBs), the most widely used class of CCBs. There are at least five different types of calcium channels in Homo sapiens: L-, N-, P/Q-, R- and T-type. CCBs target L-type calcium channels, the major channel in muscle cells that mediates contraction. Similar to other DHP CCBs, isradipine binds directly to inactive calcium channels stabilizing their inactive conformation. Since arterial smooth muscle depolarizations are longer in duration than cardiac muscle depolarizations, inactive channels are more prevalent in smooth muscle cells. Alternative splicing of the alpha-1 subunit of the channel gives isradipine additional arterial selectivity. At therapeutic sub-toxic concentrations, isradipine has little effect on cardiac myocytes and conduction cells.
Dược Động Học :
▧ Absorption :
Isradipine is 90%-95% absorbed and is subject to extensive first-pass metabolism, resulting in a bioavailability of about 15%-24%.
▧ Protein binding :
95%
▧ Metabolism :
Hepatic. Completely metabolized prior to excretion and no unchanged drug is detected in the urine.
▧ Route of Elimination :
Approximately 60% to 65% of an administered dose is excreted in the urine and 25% to 30% in the feces.
▧ Half Life :
8 hours
Độc Tính : Symptoms of overdose include lethargy, sinus tachycardia, and transient hypotension. Significant lethality was observed in mice given oral doses of over 200 mg/kg and rabbits given about 50 mg/kg of isradipine. Rats tolerated doses of over 2000 mg/kg without effects on survival.
Chỉ Định : For the management of mild to moderate essential hypertension. It may be used alone or concurrently with thiazide-type diuretics.
Tương Tác Thuốc :
  • Artemether Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
  • Lumefantrine Additive QTc-prolongation may occur. Concomitant therapy should be avoided.
  • Quinupristin This combination presents an increased risk of toxicity
  • Tacrolimus Additive QTc-prolongation may occur increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.
  • Telithromycin Telithromycin may reduce clearance of Isradipine. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Isradipine if Telithromycin is initiated, discontinued or dose changed.
  • Thiopental The CYP3A4 inducer, Thiopental, may increase the metabolism and clearance of Isradipine, a CYP3A4 substrate. Monitor for changes in the therapeutic/adverse effects of Isradipine if Thiopental is initiated, discontinued or dose changed.
  • Thiothixene May cause additive QTc-prolonging effects. Increased risk of ventricular arrhythmias. Consider alternate therapy. Thorough risk:benefit assessment is required prior to co-administration.
  • Tipranavir Tipranavir may decrease the metabolism and clearance of the calcium channel blocker, Isradipine. Monitor for changes in Isradipine therapeutic and adverse effects if Tipranavir is initiated, discontinued or dose changed.
  • Toremifene Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Consider alternate therapy. A thorough risk:benefit assessment is required prior to co-administration.
  • Treprostinil Additive hypotensive effect. Monitor antihypertensive therapy during concomitant use.
  • Trimipramine Additive QTc-prolongation may occur, increasing the risk of serious ventricular arrhythmias. Concomitant therapy should be used with caution.
  • Voriconazole Voriconazole, a strong CYP3A4 inhibitor, may increase the serum concentration of isradipine by decreasing its metabolism. Additive QTc prolongation may also occur. Consider alternate therapy or monitor for changes in the therapeutic and adverse effects of isradipine if voriconazole is initiated, discontinued or dose changed.
  • Vorinostat Additive QTc prolongation may occur. Consider alternate therapy or monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).
  • Ziprasidone Additive QTc-prolonging effects may increase the risk of severe arrhythmias. Concomitant therapy is contraindicated.
  • Zuclopenthixol Additive QTc prolongation may occur. Consider alternate therapy or use caution and monitor for QTc prolongation as this can lead to Torsade de Pointes (TdP).
Liều Lượng & Cách Dùng : Capsule - Oral - 2.5 mg
Capsule - Oral - 5 mg
Tablet, extended release - Oral - 10 mg
Tablet, extended release - Oral - 5 mg
Dữ Kiện Thương Mại
Giá thị trường
Nhà Sản Xuất
Đóng gói
Tài Liệu Tham Khảo Thêm
drugbank
http://www.drugbank.ca/drugs/DB00270
PubChem Compound
http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=3784
PubChem Substance
http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=46505034
KEGG Drug
http://www.genome.jp/dbget-bin/www_bget?drug:D00349
ChemSpider
http://www.chemspider.com/Chemical-Structure.3652.html
National Drug Code Directory
http://www.hipaaspace.com/Medical_Billing/Coding/National.Drug.Codes/PDF/0173-0784-01
PharmGKB
http://www.pharmgkb.org/drug/PA450131
Wikipedia
http://en.wikipedia.org/wiki/Isradipine
RxList
http://www.rxlist.com/cgi/generic2/israd.htm
PDRhealth
http://www.pdrhealth.com/drug_info/rxdrugprofiles/drugs/dyn1152.shtml
Drugs.com
http://www.drugs.com/cdi/isradipine.html
... loading
... loading