Tìm theo
Amlodipine
Các tên gọi khác (7 ) :
  • (RS)-3-ethyl 5-methyl 2-[(2-aminoethoxy)methyl]-4-(2-chlorophenyl)-6-methyl-1,4-dihydropyridine-3,5-dicarboxylate
  • 3-Ethyl 5-methylester, (±)-2-[(2-aminoethoxy)methyl]-4-(o-chlorophenyl)-1,4-dihydro-6-methyl-3,5-pyridinedicarboxylate
  • 3-Ethyl-5-methyl (+-)-2-(2-aminoethoxymethyl)-4-(O-chlorophenyl)-1,4-dihydro-6-methyl-3,5-pyridinedicarboxylate
  • Amlodipine
  • Amlodipine free base
  • Amlodipino
  • Amlodipinum
Thuốc tim mạch
Thuốc Gốc
Small Molecule
CAS: 88150-42-9
ATC: C08CA01
ĐG : Actavis Group , http://www.actavis.com
CTHH: C20H25ClN2O5
PTK: 408.876
Amlodipine is a long-acting 1,4-dihydropyridine calcium channel blocker. It acts primarily on vascular smooth muscle cells by stabilizing voltage-gated L-type calcium channels in their inactive conformation. By inhibiting the influx of calcium in smooth muscle cells, amlodipine prevents calcium-dependent myocyte contraction and vasoconstriction. A second proposed mechanism for the drug’s vasodilatory effects involves pH-dependent inhibition of calcium influx via inhibition of smooth muscle carbonic anhydrase. Some studies have shown that amlodipine also exerts inhibitory effects on voltage-gated N-type calcium channels. N-type calcium channels located in the central nervous system may be involved in nociceptive signaling and pain sensation. Amlodipine is used to treat hypertension and chronic stable angina.
Nhận Dạng Quốc Tế & Đặc Tính Hóa Học
Công thức hóa học
C20H25ClN2O5
Phân tử khối
408.876
Monoisotopic mass
408.145199627
InChI
InChI=1S/C20H25ClN2O5/c1-4-28-20(25)18-15(11-27-10-9-22)23-12(2)16(19(24)26-3)17(18)13-7-5-6-8-14(13)21/h5-8,17,23H,4,9-11,22H2,1-3H3
InChI Key
InChIKey=HTIQEAQVCYTUBX-UHFFFAOYSA-N
IUPAC Name
3-ethyl 5-methyl 2-[(2-aminoethoxy)methyl]-4-(2-chlorophenyl)-6-methyl-1,4-dihydropyridine-3,5-dicarboxylate
Traditional IUPAC Name
amlodipine
SMILES
CCOC(=O)C1=C(COCCN)NC(C)=C(C1C1=CC=CC=C1Cl)C(=O)OC
Độ tan chảy
178-179 °C
Độ hòa tan
75.3 mg/L
logP
3.00
logS
-4.7
pKa (Strongest Basic)
9.45
PSA
99.88 Å2
Refractivity
108.64 m3·mol-1
Polarizability
42.29 Å3
Rotatable Bond Count
10
H Bond Acceptor Count
5
H Bond Donor Count
2
Physiological Charge
1
Number of Rings
2
Bioavailability
1
Rule of Five
true
Ghose Filter
true
Dược Lực Học : Amlodipine 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. It was widely accepted that DHP CCBs target L-type calcium channels, the major channel in muscle cells that mediate contraction; however, some studies have indicated that amlodipine also binds to and inhibits N-type calcium channels (see references in Targets section). Similar to other DHP CCBs, amlodipine binds directly to inactive L-type 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 amlodipine additional arterial selectivity. At therapeutic sub-toxic concentrations, amlodipine has little effect on cardiac myocytes and conduction cells.
Cơ Chế Tác Dụng : Amlodipine is a long-acting 1,4-dihydropyridine calcium channel blocker. It acts primarily on vascular smooth muscle cells by stabilizing voltage-gated L-type calcium channels in their inactive conformation. By inhibiting the influx of calcium in smooth muscle cells, amlodipine prevents calcium-dependent myocyte contraction and vasoconstriction. A second proposed mechanism for the drug’s vasodilatory effects involves pH-dependent inhibition of calcium influx via inhibition of smooth muscle carbonic anhydrase. Some studies have shown that amlodipine also exerts inhibitory effects on voltage-gated N-type calcium channels. N-type calcium channels located in the central nervous system may be involved in nociceptive signaling and pain sensation. Amlodipine is used to treat hypertension and chronic stable angina. Amlodipine 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 amlodipine result in an overall decrease in blood pressure. Amlodipine is a long-acting CCB that may be used to treat mild to moderate essential hypertension and exertion-related angina (chronic stable angina). Another possible mechanism is that amlodipine inhibits vascular smooth muscle carbonic anhydrase I activity causing cellular pH increases which may be involved in regulating intracelluar calcium influx through calcium channels.
Dược Động Học :
▧ Absorption :
Amlodipine is slowly and almost completely absorbed from the gastrointestinal tract. Peak plasma concentrations are reached 6-12 hour following oral administration. Its estimated bioavailability is 64-90%. Absorption is not affected by food.
▧ Protein binding :
97.5%
▧ Metabolism :
Hepatic. Metabolized extensively (90%) to inactive metabolites via the cytochrome P450 3A4 isozyme.
▧ Route of Elimination :
Amlodipine is extensively (about 90%) converted to inactive metabolites via hepatic metabolism with 10% of the parent compound and 60% of the metabolites excreted in the urine.
▧ Half Life :
30-50 hours
Độc Tính : Gross overdosage could result in excessive peripheral vasodilatation and possibly reflex tachycardia. Marked and probably prolonged systemic hypotension up to an including shock with fatal outcome have been reported.
Chỉ Định : For the treatment of hypertension and chronic stable angina.
Tương Tác Thuốc :
  • Diltiazem Diltiazem may increase the serum concentration of amlodipine. Concomitant therapy will result in additive hypotensive effects. Monitor for changes in the hypotensive effect of amlodipine if diltiazem is initiated, discontinued or dose changed.
  • Quinupristin This combination presents an increased risk of toxicity
  • Tacrine The metabolism of Tacrine, a CYP1A2 substrate, may be reduced by Amlopidine, a CYP1A2 inhibitors. Monitor the efficacy and toxicity of Tacrine if Amlopidine is initiated, discontinued or if the dose is changed.
  • Telaprevir Telaprevir inhibits the metabolism of amlodipine and concomitant therapy is contraindicated.
  • Telithromycin Telithromycin may reduce clearance of Amlopidine. Consider alternate therapy or monitor for changes in the therapeutic/adverse effects of Amlopidine if Telithromycin is initiated, discontinued or dose changed.
  • Thiopental The CYP3A4 inducer, Thiopental, may increase the metabolism and clearance of Amlodipine, a CYP3A4 substrate. Monitor for changes in the therapeutic/adverse effects of Amlodipine if Thiopental is initiated, discontinued or dose changed.
  • Tipranavir Tipranavir may decrease the metabolism and clearance of the calcium channel blocker, Amlopidine. Monitor for changes in Amlopidine therapeutic and toxic effects if Tipranavir is initiated, discontinued or dose changed.
  • Tizanidine Amlopidine may decrease the metabolism and clearance of Tizanidine. Consider alternate therapy or use caution during co-administration.
  • Treprostinil Additive hypotensive effect. Monitor antihypertensive therapy during concomitant use.
  • Voriconazole Voriconazole may increase the serum concentration of amlodipine by decreasing its metabolism. Monitor for changes in the therapeutic and adverse effects of amlodipine if voriconazole is initiated, discontinued or dose changed.
Liều Lượng & Cách Dùng : Tablet - Oral - 10 mg
Tablet - Oral - 2.5 mg
Tablet - Oral - 5 mg
Dữ Kiện Thương Mại
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Đóng gói
Tài Liệu Tham Khảo Thêm
drugbank
http://www.drugbank.ca/drugs/DB00381
PubChem Compound
http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=2162
PubChem Substance
http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?sid=46507214
KEGG Compound
http://www.genome.jp/dbget-bin/www_bget?cpd:C06825
ChemSpider
http://www.chemspider.com/Chemical-Structure.2077.html
National Drug Code Directory
http://www.hipaaspace.com/Medical_Billing/Coding/National.Drug.Codes/PDF/53808-0200-1
PharmGKB
http://www.pharmgkb.org/drug/PA448388
Wikipedia
http://en.wikipedia.org/wiki/Amlodipine
RxList
http://www.rxlist.com/cgi/generic/amlod2.htm
PDRhealth
http://www.pdrhealth.com/drugs/rx/rx-mono.aspx?contentFileName=nor1306.html&contentName=Norvasc&contentId=538
Drugs.com
http://www.drugs.com/amlodipine.html
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