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药品详细

Amlodipine(氨氯地平)

化学结构式图
中文名
氨氯地平
英文名
Amlodipine
分子式
C20H25ClN2O5
化学名
3-ethyl 5-methyl 2-[(2-aminoethoxy)methyl]-4-(2-chlorophenyl)-6-methyl-1,4-dihydropyridine-3,5-dicarboxylate
分子量
Average: 408.876
Monoisotopic: 408.145199627
CAS号
88150-42-9
ATC分类
C08C 未知
药物类型
small molecule
阶段
approved
商品名
Amlocard (AWD (Germany));Amlodis (Eczacibasi (Turkey));Amvaz (Reddy (Malaysia));Coroval (Sandoz (Argentina));Lipinox;Lotrel;Norvasc (Pfizer);
同义名
Amlodipine Benzenesulfonate;Amlodipine Besilate;Amlodipine Besylate;Amlodipine Free Base;Amlodipino [Spanish];Amlodipinum [Latin];
基本介绍

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.

生产厂家
  • Actavis totowa llc
  • Alkem laboratories ltd
  • Amneal pharmaceuticals ny llc
  • Apotex inc
  • Aurobindo pharma ltd
  • Caraco pharmaceutical laboratories ltd
  • Dr reddys laboratories inc
  • Dr reddys laboratories ltd
  • Gedeon richter usa inc
  • Genpharm inc
  • Glenmark generics ltd
  • Invagen pharmaceuticals inc
  • Lek pharmaceuticals dd
  • Lupin ltd
  • Matrix laboratories ltd
  • Mutual pharmacal co
  • Mylan laboratories inc
  • Orchid healthcare
  • Pfizer inc
  • Ranbaxy laboratories ltd
  • Roxane laboratories inc
  • Synthon pharmaceuticals inc
  • Teva pharmaceuticals usa inc
  • Torrent pharmaceuticals ltd
  • Upsher smith laboratories inc
  • Vintage pharmaceuticals llc
  • Watson laboratories inc
  • Wockhardt ltd
  • World gen llc
  • Zydus pharmaceuticals usa inc
封装厂家
参考
Synthesis Reference Not Available
General Reference
  1. Nayler WG, Gu XH: The unique binding properties of amlodipine: a long-acting calcium antagonist. J Hum Hypertens. 1991 Aug;5 Suppl 1:55-9. Pubmed
  2. van Zwieten PA: Amlodipine: an overview of its pharmacodynamic and pharmacokinetic properties. Clin Cardiol. 1994 Sep;17(9 Suppl 3):III3-6. Pubmed
剂型
规格
化合物类型
Type small molecule
Classes
  • Dihydropyridines
  • Carboxylic Acids and Derivatives
  • Benzene and Derivatives
  • Halobenzenes
Substructures
  • Dihydropyridines
  • Carboxylic Acids and Derivatives
  • Acetates
  • Aliphatic and Aryl Amines
  • Ethers
  • Benzene and Derivatives
  • Aryl Halides
  • Halobenzenes
  • Enamines
  • Heterocyclic compounds
  • Aromatic compounds
适应症
ANTIHYPERTENSIVES 降血压;
药理
Indication For the treatment of hypertension and chronic stable angina.
Pharmacodynamics 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.
Mechanism of action 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.
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.
Volume of distribution Not Available
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
Clearance Not Available
Toxicity 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.
Affected organisms
  • Humans and other mammals
Pathways
Pathway Name SMPDB ID
Smp00376 Amlodipine Pathway SMP00376
理化性质
Properties
State solid
Experimental Properties
Property Value Source
melting point 178-179 °C Not Available
water solubility 75.3 mg/L Not Available
logP 3.00 AUSTIN,RP ET AL. (1995)
Predicted Properties
Property Value Source
water solubility 7.40e-03 g/l ALOGPS
logP 2.22 ALOGPS
logP 1.64 ChemAxon
logS -4.7 ALOGPS
pKa (strongest basic) 9.45 ChemAxon
physiological charge 1 ChemAxon
hydrogen acceptor count 5 ChemAxon
hydrogen donor count 2 ChemAxon
polar surface area 99.88 ChemAxon
rotatable bond count 10 ChemAxon
refractivity 108.64 ChemAxon
polarizability 42.29 ChemAxon
药物相互作用
Drug Interaction
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.
食物相互作用
  • Avoid natural licorice.
  • Grapefruit down regulates post-translational expression of CYP3A4, the major metabolizing enzyme of amlodipine. Grapefruit, in all forms (e.g. whole fruit, juice and rind), can significantly increase serum levels of amlodipine and may cause toxicity. Avoid grapefruit products while on this medication.
  • Take without regard to meals.

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