QuickView for Amlodipine (compound)

Summary
General Info

PubChem

PubChem Compound 10231529

Name:	Amlodipine
PubChem Compound ID:	10231529
Description:	A long-acting dihydropyridine calcium channel blocker. It is effective in the treatment of ANGINA PECTORIS and HYPERTENSION.
Molecular formula:	C₂₆H₃₁ClN₂O₈S
Molecular weight:	567.052 g/mol

DrugBank

Identification

Name:	Amlodipine
Name (isomeric):	DB00381
Drug Type:	small molecule
Description:	A long-acting dihydropyridine calcium channel blocker. It is effective in the treatment of ANGINA PECTORIS and HYPERTENSION.
Synonyms:	Amlodipine Benzenesulfonate; Amlodipino [Spanish]; Amlodipinum [Latin]; Amlodipine Besylate; Amlodipine Besilate; Amlodipine Free Base
Brand:	Amlocard, Norvasc, Lipinox, Amlodis, Lotrel, Amvaz, Coroval
Brand name mixture:	Exforge(amlodipine + valsartan), Coroval B(amlodipine + benazepril), Lotrel(amlodipine + benazepril), Caduet(amlodipine + atorvastatin), Azor(amlodipine + olmesartan)
Category:	Vasodilator Agents, Calcium Channel Blockers, Antihypertensive Agents, Antianginals
CAS number:	88150-42-9

Pharmacology

Indication:	For the treatment of hypertension and chronic stable angina.
Pharmacology:	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 co... show more » 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. show less «
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 ... show more » 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. show less «
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%
Biotransformation:	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
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

Interactions

Food interaction:

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.

Avoid natural licorice.

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.
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.
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.
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.
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.