| Systematic (IUPAC) name | |
|---|---|
| (RS)-3-ethyl 5-methyl 2-[(2-aminoethoxy)methyl]-4-(2-chlorophenyl)-6-methyl-1,4-dihydropyridine-3,5-dicarboxylate | |
| Clinical data | |
| Trade names | Norvasc |
| AHFS/Drugs.com | monograph |
| MedlinePlus | a692044 |
| Licence data | US FDA:link |
| Pregnancy cat. | C(AU) C(US) |
| Legal status | POM (UK) ℞-only (US) |
| Routes | Oral (tablets) |
| Pharmacokinetic data | |
| Bioavailability | 64 to 90% |
| Metabolism | Hepatic |
| Half-life | 30 to 50 hours |
| Excretion | Renal |
| Identifiers | |
| CAS number | 88150-42-9 |
| ATC code | C08CA01 |
| PubChem | CID 2162 |
| DrugBank | APRD00520 |
| ChemSpider | 2077 |
| UNII | 1J444QC288 |
| KEGG | D07450 |
| ChEBI | CHEBI:2668 |
| ChEMBL | CHEMBL1491 |
| Chemical data | |
| Formula | C20H25ClN2O5 |
| Mol. mass | 408.879 g/mol |
| SMILES | eMolecules & PubChem |
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Amlodipine (Norvasc, Pfizer, and generics) (as besylate, mesylate or maleate) is a long-acting calcium channel blocker (dihydropyridine (DHP) class) used as an anti-hypertensive and in the treatment of angina. Like other calcium channel blockers, amlodipine acts by relaxing the smooth muscle in the arterial wall, decreasing total peripheral resistance and hence reducing blood pressure; in angina it increases blood flow to the heart muscle (although DHP-class calcium channel blockers are more selective for arteries than myocardium, as the cardiac calcium channels are not of the dihydropyridine-type).
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Amlodipine is used in the management of hypertension, and coronary artery disease.[1]
Adverse side effects of the use of amlodipine may be:[2]
The acute oral toxicity (LD50) of amlodipine in mice is 37 mg/kg.[4]
Amlodipine is a dihydropyridine calcium antagonist (calcium ion antagonist or slow-channel blocker) that inhibits the transmembrane influx of calcium ions into vascular smooth muscle and cardiac muscle. Experimental data suggest that amlodipine binds to both dihydropyridine and nondihydropyridine binding sites. The contractile processes of cardiac muscle and vascular smooth muscle are dependent upon the movement of extracellular calcium ions into these cells through specific ion channels. Amlodipine inhibits calcium ion influx across cell membranes selectively, with a greater effect on vascular smooth muscle cells than on cardiac muscle cells. Negative inotropic effects can be detected in vitro but such effects have not been seen in intact animals at therapeutic doses. Serum calcium concentration is not affected by amlodipine. Within the physiologic pH range, amlodipine is an ionized compound (pKa=8.6), and its kinetic interaction with the calcium channel receptor is characterized by a gradual rate of association and dissociation with the receptor binding site, resulting in a gradual onset of effect.
Amlodipine is a peripheral arterial vasodilator that acts directly on vascular smooth muscle to cause a reduction in peripheral vascular resistance and reduction in blood pressure.
The precise mechanisms by which amlodipine relieves angina have not been fully delineated, but are thought to include the following:
Amlodipine is almost entirely metabolised to inactive metabolites. 10% of the parent substance and 60% of the metabolites are excreted in urine.
Amlodipine is a chiral calcium antagonist, currently on the market and in therapeutic use as a racemate [1:1 mixture of (R)-(+)- and (S)-(–)-amlodipine][5] A method for the semi-preparative chromatographic purification of the enantiomers (S)-(–)-amlodipine and (R)-(+)-amlodipine has been reported.[6]
Pfizer patent protection on Norvasc lasted until 2007. Total patent expiration occurred later in 2007.[7] A number of generic versions are available.
In the United Kingdom tablets of amlodipine from different suppliers may contain different salts. The strength of the tablets is expressed in terms of amlodipine base, i.e., without the salt. Tablets containing different salts are therefore considered interchangeable.
The efficacy and tolerability of a fixed-dose combination of amlodipine 5 mg and perindopril 4 mg, an angiotensin converting enzyme (ACE) inhibitor, have recently been confirmed in a prospective, observational multicentre trial of 1250 hypertensive patients.[8]
Amlodipine is marketed as:
India