Identification

Name
Amlodipine
Accession Number
DB00381
Description

Amlodipine, initially approved by the FDA in 1987, is a popular antihypertensive drug belonging to the group of drugs called dihydropyridine calcium channel blockers. Due to their selectivity for the peripheral blood vessels, dihydropyridine calcium channel blockers are associated with a lower incidence of myocardial depression and cardiac conduction abnormalities than other calcium channel blockers 5.

Amlodipine is commonly used in the treatment of high blood pressure and angina. Amlodipine has antioxidant properties and an ability to enhance the production of nitric oxide (NO), an important vasodilator that decreases blood pressure 3. The option for single daily dosing of amlodipine is an attractive feature of this drug Label.

Type
Small Molecule
Groups
Approved
Structure
Thumb
Weight
Average: 408.876
Monoisotopic: 408.145199627
Chemical Formula
C20H25ClN2O5
Synonyms
  • (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
  • Amlodipine
  • Amlodipine free base
  • Amlodipino
  • Amlodipinum

Pharmacology

Indication

Amlodipine may be used alone or in combination with other antihypertensive and antianginal agents for the treatment of the following conditions Label:

• Hypertension

• Coronary artery disease

• Chronic stable angina

• Vasospastic angina (Prinzmetal’s or Variant angina)

• Angiographically documented coronary artery disease in patients without heart failure or an ejection fraction < 40%

Associated Conditions
Contraindications & Blackbox Warnings
Learn about our commercial Contraindications & Blackbox Warnings data.
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Pharmacodynamics

General pharmacodynamic effects

Amlodipine has a strong affinity for cell membranes, modulating calcium influx by inhibiting selected membrane calcium channels. This drug's unique binding properties allow for its long-acting action and less frequent dosing regimen 1, Label.

Hemodynamic effects

After the administration of therapeutic doses of amlodipine to patients diagnosed with hypertension, amlodipine causes vasodilation, which results in a reduction of supine and standing blood pressure. During these blood pressure reductions, there are no clinically significant changes in heart rate or plasma catecholamine levels with long-term use. Acute intravenous administration of amlodipine reduces arterial blood pressure and increases heart rate in patients with chronic stable angina, however, chronic oral administration of amlodipine in clinical studies did not cause clinically significant alterations in heart rate or blood pressures in patients diagnosed with angina and normal blood pressure. With long-term, once daily oral administration, antihypertensive effectiveness is maintained for at least 24 hours Label.

Electrophysiologic effects

Amlodipine does not change sinoatrial (SA) nodal function or atrioventricular (AV) conduction in animals or humans. In patients who were diagnosed with chronic stable angina, the intravenous administration of 10 mg of amlodipine did not cause clinically significant alterations A-H and H-V conduction and sinus node recovery time after cardiac pacing. Patients administered amlodipine with concomitant beta-blockers produced similar results. In clinical trials in which amlodipine was given in combination with beta-blockers to patients diagnosed with hypertension or angina, no adverse effects on electrocardiographic parameters were noted. In clinical studies comprised of angina patients alone, amlodipine did not change electrocardiographic intervals or produce high degrees of AV block Label.

Effects on angina

Amlodipine relieves the symptoms of chest pain associated with angina. In patients diagnosed with angina, daily administration of a single amlodipine dose increases total exercise time, the time to angina onset, and the time to 1 mm ST-segment depression on ECG studies, decreases anginal attack frequency, and decreases the requirement for nitroglycerin tablets 9.

Mechanism of action

Mechanism of action on blood pressure

Amlodipine is considered a peripheral arterial vasodilator that exerts its action directly on vascular smooth muscle to lead to a reduction in peripheral vascular resistance, causing a decrease in blood pressure. Amlodipine is a dihydropyridine calcium antagonist (calcium ion antagonist or slow-channel blocker) that inhibits the influx of calcium ions into both vascular smooth muscle and cardiac muscle. Experimental studies imply that amlodipine binds to both dihydropyridine and nondihydropyridine binding sites, located on cell membranes. The contraction of cardiac muscle and vascular smooth muscle are dependent on the movement of extracellular calcium ions into these cells by specific ion channels. Amlodipine blocks calcium ion influx across cell membranes with selectivity. A stronger effect of amlodipine is exerted on vascular smooth muscle cells than on cardiac muscle cells Label. Direct actions of amlodipine on vascular smooth muscle result in reduced blood pressure 9.

Mechanism of action in angina

The exact mechanism by which amlodipine relieves the symptoms of angina have not been fully elucidated to this date, however, the mechanism of action is likely twofold:

Amlodipine has a dilating effect on peripheral arterioles, reducing the total peripheral resistance (afterload) against which the cardiac muscle functions. Since the heart rate remains stable during amlodipine administration, the reduced work of the heart reduces both myocardial energy use and oxygen requirements 9.

Dilatation of the main coronary arteries and coronary arterioles, both in healthy and ischemic areas, is another possible mechanism of amlodipine reduction of blood pressure. The dilatation causes an increase in myocardial oxygen delivery in patients experiencing coronary artery spasm (Prinzmetal's or variant angina) and reduces coronary vasoconstriction caused by smoking 9.

TargetActionsOrganism
AVoltage-dependent L-type calcium channel subunit alpha-1C
inhibitor
Humans
UVoltage-dependent N-type calcium channel subunit alpha-1B
inhibitor
Humans
UVoltage-dependent L-type calcium channel subunit beta-1
inhibitor
Humans
UVoltage-dependent calcium channel subunit alpha-2/delta-3
inhibitor
Humans
UCarbonic anhydrase 1
inhibitor
Humans
USphingomyelin phosphodiesterase
inhibitor
Humans
AVoltage-dependent T-type calcium channel subunit alpha-1I
inhibitor
Humans
UVoltage-dependent N-type calcium channel
inhibitor
Humans
Absorption

Amlodipine absorbed slowly and almost completely from the gastrointestinal tract. Peak plasma concentrations are achieved 6-12 hours after oral administration. The estimated bioavailability of amlodipine is 64-90%. Steady-state plasma amlodipine levels are achieved after 7-8 days of consecutive daily dosing. Absorption is not affected by food Label.

Volume of distribution

21 L/kg 5, 6.

Protein binding

About 98% 5, 6.

Metabolism

Amlodipine is heavily (approximately 90%) converted to inactive metabolites via hepatic breakdown with 10% of the parent compound and 60% of the metabolites found excreted in the urine. Ex vivo studies have shown that about 93% of the circulating drug is bound to plasma proteins in hypertensive patients Label. Characteristics that add to amlodipine's unique pharmacologic profile include nearly complete absorption, late-peak plasma concentrations, high bioavailability, and slow hepatic breakdown 2.

Hover over products below to view reaction partners

Route of elimination

Elimination from the plasma occurs in a biphasic with a terminal elimination half-life of about 30–50 hours. Steady-state plasma levels of amlodipine are reached after 7-8 days of consecutive daily dosing Label. Amlodipine is 10% excreted as unchanged drug in the urine. Amlodipine can be initiated at normal doses in patients diagnosed with renal failure 9, Label.

Half-life

The terminal elimination half-life of about 30–50 hours Label.

Plasma elimination half-life is 56 hours in patients with impaired hepatic function, titrate slowly when administering this drug to patients with severe hepatic impairment Label.

Clearance

Total body clearance (CL) has been calculated as 7 ± 1.3 ml/min/kg (0.42 ± 0.078 L/ h/kg) in healthy volunteers 5, 6.

Elderly patients show a reduced clearance of amlodipine with an AUC (area under the curve) increase of about 40–60%, and a lower initial dose may be required Label.

Adverse Effects
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Toxicity

Acute oral toxicity (LD50): 37 mg/kg (mouse) MSDS.

Overdose

An overdose of amlodipine could result in a high degree of peripheral vasodilatation with a possibility of reflex tachycardia. Significant and prolonged hypotension leading to shock and fatal outcomes have been reported Label.

Carcinogenesis, mutagenesis, impairment of fertility

Rats and mice treated with amlodipine maleate in the diet on a long-term basis for up to 2 years demonstrated no evidence of a carcinogenic effect of the drug. For the mouse, the highest dose was comparable to the maximum recommended human dose of 10 mg amlodipine per day. For the rat, the highest dose was measured to be about twice the maximum recommended human dose Label.

Mutagenicity studies using amlodipine maleate showed no drug-related gene or chromosomal effects Label.

There was no impact on the fertility of rats given oral amlodipine maleate (males for 64 days and females for 14 days before mating) at doses up to 10 mg amlodipine/kg/day (8 times the maximum recommended human dose) Label.

Use in pregnancy

The safety of amlodipine in human pregnancy or lactation has not been proven. Amlodipine is therefore considered a pregnancy category C drug 9. Use amlodipine only if the potential benefit justifies the potential risk Label.

Use in nursing

Discontinue when administering amlodipine Label.

Affected organisms
  • Humans and other mammals
Pathways
PathwayCategory
Amlodipine Action PathwayDrug action
Pharmacogenomic Effects/ADRs
Interacting Gene/EnzymeAllele nameGenotype(s)Defining Change(s)Type(s)DescriptionDetails
Natriuretic peptides A---(A;A)AA alleleEffect Directly StudiedPatients with this genotype have increased risk of adverse cardiovascular outcomes with diuretics.Details

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
AbametapirThe serum concentration of Amlodipine can be increased when it is combined with Abametapir.
AcarboseThe risk or severity of hypoglycemia can be increased when Amlodipine is combined with Acarbose.
AcebutololThe risk or severity of bradycardia can be increased when Amlodipine is combined with Acebutolol.
AceclofenacAceclofenac may decrease the antihypertensive activities of Amlodipine.
AcemetacinAcemetacin may decrease the antihypertensive activities of Amlodipine.
AcetaminophenThe metabolism of Amlodipine can be increased when combined with Acetaminophen.
AcetohexamideThe risk or severity of hypoglycemia can be increased when Amlodipine is combined with Acetohexamide.
AcetyldigitoxinAmlodipine may increase the arrhythmogenic activities of Acetyldigitoxin.
Acetylsalicylic acidAcetylsalicylic acid may decrease the antihypertensive activities of Amlodipine.
AdenosineAmlodipine may increase the arrhythmogenic activities of Adenosine.
Additional Data Available
  • Extended Description
    Extended Description

    Extended description of the mechanism of action and particular properties of each drug interaction.

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  • Severity
    Severity

    A severity rating for each drug interaction, from minor to major.

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  • Evidence Level
    Evidence Level

    A rating for the strength of the evidence supporting each drug interaction.

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  • Action
    Action

    An effect category for each drug interaction. Know how this interaction affects the subject drug.

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Food Interactions
  • Avoid grapefruit products.
  • Avoid natural licorice.
  • Take with or without food. The absorption is unaffected by food.

Products

Product Ingredients
IngredientUNIICASInChI Key
Amlodipine besylate864V2Q084H111470-99-6ZPBWCRDSRKPIDG-UHFFFAOYSA-N
Amlodipine camsylate0V8DBY3260652969-01-2UXKMFEPPKJZDAR-STOWLHSFSA-N
Amlodipine maleateCQ27G2BZJM88150-47-4TZNOWAJJWCGILX-BTJKTKAUSA-N
Amlodipine mesylate291Y33EZHA246852-12-0MUVFCHUBATVFPP-UHFFFAOYSA-N
Amlodipine mesylate monohydrateFAS0DJC51V440358-84-9LGWOIMCQWJLZIT-UHFFFAOYSA-N
Product Images
International/Other Brands
Aforbes (Merck) / Agen (Zentiva) / Aken (Kendrick Farmaceutica) / Amcard (Apex Pharma Ltd) / Amdepin (Cadila Pharmaceuticals) / Amdipin (Laboratorios Lafrancol) / Amilostad / Amlocard (AWD (Germany)) / Amlod / Amlodine (Sumitomo Pharmaceuticals) / Amlodipin / Amlodipin-Mepha 5/10 (Mepha Pharma AG) / Amlodipine 5 (PT KALBE FARMA Tbk) / Amlodis (Eczacibasi (Turkey)) / Amlong (Micro Labs) / Amlopin (Lek) / Amlopine (Berlin) / Amlostin (Discovery Pharmaceuticals) / Amlosun (Sun Pharmaceutical) / Amlovas (Macleods Pharmaceuticals Ltd) / Amlovasc (Dr. Reddy's Laboratories) / Amlozek (Adamed) / Amvaz (Reddy (Malaysia)) / Asomex (Emcure Pharmaceuticals) / Atecard-AM (Alembic Ltd) / Camlodin (Square) / Cardilopina / Coroval (Sandoz (Argentina)) / Dailyvasc (Xeno Pharmaceuticals) / Istin / Lama (Stadmed Private Limited) / Lodip (TIME Pharmaceuticals) / Lodopin (Merck Pakistan) / Lopin (Edruc Ltd) / Nelod (The Kemiko Pharmaceuticals Ltd) / Nopidin (Ad-din Pharmaceuticals Ltd) / Nordip / Perivasc / Pharex Amlodipine (PHAREX HealthCorp) / Tenox (Krka)
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
Act AmlodipineTabletOralTEVA Canada Limited2010-03-02Not applicableCanada flag
Act AmlodipineTabletOralTEVA Canada Limited2009-07-10Not applicableCanada flag
Act AmlodipineTabletOralTEVA Canada Limited2009-07-10Not applicableCanada flag
AmlodipineTablet10 mgOralJamp Pharma Corporation2014-09-04Not applicableCanada flag
AmlodipineTablet5 mgOralSivem Pharmaceuticals Ulc2012-06-12Not applicableCanada flag
AmlodipineTablet5 mgOralAltamed Pharma2019-12-30Not applicableCanada flag
AmlodipineTablet2.5 mgOralActavis Pharma CompanyNot applicableNot applicableCanada flag
AmlodipineTablet2.5 mgOralMeliapharm Inc2011-04-082014-06-25Canada flag
AmlodipineTablet2.5 mg/1OralCaraco Pharmaceutical Laboratories, Ltd.2008-12-15Not applicableUS flag
AmlodipineTablet10 mgOralPro Doc Limitee2009-07-22Not applicableCanada flag
Additional Data Available
  • Application Number
    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

    Learn more
  • Product Code
    Product Code

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

    Learn more
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
Accel-amlodipineTabletOralAccel Pharma Inc2010-03-052016-10-19Canada flag
Accel-amlodipineTabletOralAccel Pharma IncNot applicableNot applicableCanada flag
Accel-amlodipineTabletOralAccel Pharma Inc2010-03-052016-10-19Canada flag
Ag-amlodipineTabletOralAngita Pharma Inc.2018-06-06Not applicableCanada flag
Ag-amlodipineTabletOralAngita Pharma Inc.2014-09-25Not applicableCanada flag
Ag-amlodipineTabletOralAngita Pharma Inc.2014-09-25Not applicableCanada flag
AmlodipineTablet10 mg/1OralRemedy Repack2011-04-132011-04-14US flag
AmlodipineTablet10 mg/1OralMacleods Pharmaceuticals Limited2012-04-13Not applicableUS flag
AmlodipineTablet10 mg/1OralState of Florida DOH Central Pharmacy2013-01-01Not applicableUS flag
AmlodipineTablet5 mg/1OralMacleods Pharmaceuticals Limited2012-04-13Not applicableUS flag
Additional Data Available
  • Application Number
    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

    Learn more
  • Product Code
    Product Code

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

    Learn more
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing EndRegionImage
Aa-telmisartan-amlodipineAmlodipine (5 mg) + Telmisartan (80 mg)TabletOralAa Pharma IncNot applicableNot applicableCanada flag
Aa-telmisartan-amlodipineAmlodipine (10 mg) + Telmisartan (40 mg)TabletOralAa Pharma IncNot applicableNot applicableCanada flag
Aa-telmisartan-amlodipineAmlodipine (10 mg) + Telmisartan (80 mg)TabletOralAa Pharma IncNot applicableNot applicableCanada flag
Aa-telmisartan-amlodipineAmlodipine (5 mg) + Telmisartan (40 mg)TabletOralAa Pharma IncNot applicableNot applicableCanada flag
AmlobenzAmlodipine besylate (10 mg/1) + Benazepril hydrochloride (20 mg/1)CapsuleOralRebel Distributors2010-04-19Not applicableUS flag55111 0341 01 nlmimage10 c238e107
AmlobenzAmlodipine besylate (5 mg/1) + Benazepril hydrochloride (10 mg/1)CapsuleOralRebel Distributors2010-04-19Not applicableUS flag55111 0339 01 nlmimage10 6d03b6bd
Amlodipine and atorvastatinAmlodipine besylate (10 mg/1) + Atorvastatin calcium trihydrate (80 mg/1)Tablet, film coatedOralCadila Healthcare Limited2019-05-30Not applicableUS flag
Amlodipine and atorvastatinAmlodipine besylate (5 mg/1) + Atorvastatin calcium trihydrate (20 mg/1)Tablet, film coatedOralCadila Healthcare Limited2019-05-30Not applicableUS flag
Amlodipine and atorvastatinAmlodipine besylate (5 mg/1) + Atorvastatin calcium trihydrate (20 mg/1)Tablet, film coatedOralMylan Pharmaceuticals Inc.2014-05-21Not applicableUS flag
Amlodipine and atorvastatinAmlodipine besylate (10 mg/1) + Atorvastatin calcium trihydrate (40 mg/1)Tablet, film coatedOralCadila Healthcare Limited2019-05-30Not applicableUS flag
Unapproved/Other Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing EndRegionImage
HypertenipineAmlodipine besylate (2.5 mg/1) + Arginine (90 mg/1)KitOralPhysician Therapeutics Llc2011-07-07Not applicableUS flag

Categories

ATC Codes
C09XA54 — Aliskiren, amlodipine and hydrochlorothiazideC10BX07 — Rosuvastatin, amlodipine and lisinoprilC09BB03 — Lisinopril and amlodipineC09BB04 — Perindopril and amlodipineC07FB07 — Bisoprolol and amlodipineC09DB06 — Losartan and amlodipineC07FB12 — Nebivolol and amlodipineC09DB05 — Irbesartan and amlodipineC09XA53 — Aliskiren and amlodipineC10BX03 — Atorvastatin and amlodipineC07FB13 — Metoprolol and amlodipineC08CA01 — AmlodipineC09BX04 — Perindopril, bisoprolol and amlodipineC09BX03 — Ramipril, amlodipine and hydrochlorothiazideC09DB04 — Telmisartan and amlodipineC09DX03 — Olmesartan medoxomil, amlodipine and hydrochlorothiazideC08GA02 — Amlodipine and diureticsC09DB07 — Candesartan and amlodipineC09DX06 — Candesartan, amlodipine and hydrochlorothiazideC09BX01 — Perindopril, amlodipine and indapamideC10BX11 — Atorvastatin, amlodipine and perindoprilC09DB02 — Olmesartan medoxomil and amlodipineC10BX09 — Rosuvastatin and amlodipineC08CA51 — Amlodipine and celecoxibC09DX01 — Valsartan, amlodipine and hydrochlorothiazideC09DB09 — Fimasartan and amlodipineC09DB01 — Valsartan and amlodipineC10BX14 — Rosuvastatin, amlodipine and perindoprilC09BB07 — Ramipril and amlodipineC09DX07 — Irbesartan, amlodipine and hydrochlorothiazide
Drug Categories
Chemical TaxonomyProvided by Classyfire
Description
This compound belongs to the class of organic compounds known as dihydropyridinecarboxylic acids and derivatives. These are compounds containing a dihydropyridine moiety bearing a carboxylic acid group.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Pyridines and derivatives
Sub Class
Hydropyridines
Direct Parent
Dihydropyridinecarboxylic acids and derivatives
Alternative Parents
Chlorobenzenes / Aryl chlorides / Dicarboxylic acids and derivatives / Vinylogous amides / Methyl esters / Enoate esters / Amino acids and derivatives / Azacyclic compounds / Dialkyl ethers / Dialkylamines
show 7 more
Substituents
Alpha,beta-unsaturated carboxylic ester / Amine / Amino acid or derivatives / Aromatic heteromonocyclic compound / Aryl chloride / Aryl halide / Azacycle / Benzenoid / Carbonyl group / Carboxylic acid derivative
show 25 more
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
ethyl ester, primary amino compound, methyl ester, monochlorobenzenes, dihydropyridine (CHEBI:2668)

Chemical Identifiers

UNII
1J444QC288
CAS number
88150-42-9
InChI Key
HTIQEAQVCYTUBX-UHFFFAOYSA-N
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
IUPAC Name
3-ethyl 5-methyl 2-[(2-aminoethoxy)methyl]-4-(2-chlorophenyl)-6-methyl-1,4-dihydropyridine-3,5-dicarboxylate
SMILES
CCOC(=O)C1=C(COCCN)NC(C)=C(C1C1=CC=CC=C1Cl)C(=O)OC

References

Synthesis Reference
US4572909
General References
  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:1834847]
  2. van Zwieten PA: Amlodipine: an overview of its pharmacodynamic and pharmacokinetic properties. Clin Cardiol. 1994 Sep;17(9 Suppl 3):III3-6. [PubMed:9156957]
  3. Fares H, DiNicolantonio JJ, O'Keefe JH, Lavie CJ: Amlodipine in hypertension: a first-line agent with efficacy for improving blood pressure and patient outcomes. Open Heart. 2016 Sep 28;3(2):e000473. doi: 10.1136/openhrt-2016-000473. eCollection 2016. [PubMed:27752334]
  4. Flynn JT, Nahata MC, Mahan JD Jr, Portman RJ: Population pharmacokinetics of amlodipine in hypertensive children and adolescents. J Clin Pharmacol. 2006 Aug;46(8):905-16. doi: 10.1177/0091270006289844. [PubMed:16855075]
  5. Meredith PA, Elliott HL: Clinical pharmacokinetics of amlodipine. Clin Pharmacokinet. 1992 Jan;22(1):22-31. doi: 10.2165/00003088-199222010-00003. [PubMed:1532771]
  6. Faulkner JK, McGibney D, Chasseaud LF, Perry JL, Taylor IW: The pharmacokinetics of amlodipine in healthy volunteers after single intravenous and oral doses and after 14 repeated oral doses given once daily. Br J Clin Pharmacol. 1986 Jul;22(1):21-5. [PubMed:2943308]
  7. FDA Approved Drug Products: Amlodipine Oral Tablets [Link]
  8. FDA Approved Drug Products: Amlodipine Oral Suspension [Link]
  9. Apo amlodipine tablets, MedSafe NZ [File]
Human Metabolome Database
HMDB0005018
KEGG Drug
D07450
KEGG Compound
C06825
PubChem Compound
2162
PubChem Substance
46507214
ChemSpider
2077
BindingDB
50088383
RxNav
17767
ChEBI
2668
ChEMBL
CHEMBL1491
Therapeutic Targets Database
DAP000139
PharmGKB
PA448388
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
PDRhealth
PDRhealth Drug Page
Wikipedia
Amlodipine
AHFS Codes
  • 24:28.08 — Dihydropyridines
FDA label
Download (270 KB)
MSDS
Download (74.5 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4Active Not RecruitingTreatmentHeart Failure With Preserved Ejection Fraction (HFpEF) / High Blood Pressure (Hypertension)1
4Active Not RecruitingTreatmentHigh Blood Pressure (Hypertension)1
4Active Not RecruitingTreatmentHypertension, Renal1
4CompletedNot AvailableHigh Blood Pressure (Hypertension)1
4CompletedDiagnosticHigh Blood Pressure (Hypertension) / Type 2 Diabetes Mellitus1
4CompletedOtherCoronary Artery Disease (CAD) / Type 2 Diabetes Mellitus1
4CompletedPreventionAtrial Fibrillation (AF)2
4CompletedPreventionCardiovascular Heart Disease / Diabetes / High Blood Pressure (Hypertension)1
4CompletedPreventionCardiovascular Heart Disease / High Blood Pressure (Hypertension)1
4CompletedPreventionCoronary Artery Atherosclerosis / High Blood Pressure (Hypertension)1

Pharmacoeconomics

Manufacturers
  • Synthon pharmaceuticals inc
  • Actavis totowa llc
  • Alkem laboratories ltd
  • Amneal pharmaceuticals ny llc
  • Apotex inc
  • Aurobindo pharma ltd
  • Caraco pharmaceutical laboratories ltd
  • 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
  • Ranbaxy laboratories ltd
  • Roxane laboratories 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
  • Pfizer inc
  • Dr reddys laboratories inc
Packagers
  • Actavis Group
  • Advanced Pharmaceutical Services Inc.
  • Amerisource Health Services Corp.
  • Amneal Pharmaceuticals
  • Apotex Inc.
  • AQ Pharmaceuticals Inc.
  • Arrow Pharm Malta Ltd.
  • A-S Medication Solutions LLC
  • Aurobindo Pharma Ltd.
  • Beijing Second Pharmaceutical Co. Ltd.
  • Blu Pharmaceuticals LLC
  • Breckenridge Pharmaceuticals
  • Bryant Ranch Prepack
  • Cadila Healthcare Ltd.
  • Camber Pharmaceuticals Inc.
  • Caraco Pharmaceutical Labs
  • Cardinal Health
  • Chemical Works Of Gedeon Richter Ltd.
  • Cobalt Pharmaceuticals Inc.
  • Comprehensive Consultant Services Inc.
  • Corepharma LLC
  • Coupler Enterprises Inc.
  • Dept Health Central Pharmacy
  • Direct Dispensing Inc.
  • Direct Pharmaceuticals Inc.
  • Dispensing Solutions
  • Diversified Healthcare Services Inc.
  • Doctor Reddys Laboratories Ltd.
  • Glenmark Generics Ltd.
  • Greenstone LLC
  • H.E. Butt Grocery Co.
  • Heartland Repack Services LLC
  • InvaGen Pharmaceuticals Inc.
  • Kaiser Foundation Hospital
  • Lake Erie Medical and Surgical Supply
  • Letco Medical Inc.
  • Lupin Pharmaceuticals Inc.
  • Major Pharmaceuticals
  • Medisca Inc.
  • Medvantx Inc.
  • Murfreesboro Pharmaceutical Nursing Supply
  • Mylan
  • Neuman Distributors Inc.
  • Norwich Pharmaceuticals Inc.
  • Novartis AG
  • Nucare Pharmaceuticals Inc.
  • Palmetto Pharmaceuticals Inc.
  • PD-Rx Pharmaceuticals Inc.
  • Pfizer Inc.
  • Pharmaceutical Utilization Management Program VA Inc.
  • Physicians Total Care Inc.
  • Preferred Pharmaceuticals Inc.
  • Prepackage Specialists
  • Prepak Systems Inc.
  • Promius Pharma
  • Qualitest
  • Rebel Distributors Corp.
  • Redpharm Drug
  • Remedy Repack
  • Roxane Labs
  • Sandhills Packaging Inc.
  • Secan Pharmaceuticals Inc.
  • Solco Healthcare US LLC
  • Southwood Pharmaceuticals
  • Stat Rx Usa
  • Stat Scripts LLC
  • Synthon Pharmaceuticals Inc.
  • Teva Pharmaceutical Industries Ltd.
  • Torrent Pharmaceuticals
  • Tya Pharmaceuticals
  • UDL Laboratories
  • US Pharmaceutical Group
  • USL Pharma Inc.
  • Va Cmop Dallas
  • Vangard Labs Inc.
  • Warner Lambert Company LLC
  • Wockhardt Ltd.
  • Zydus Pharmaceuticals
Dosage Forms
FormRouteStrength
Tablet, coatedOral10 mg
Tablet10 MG
Tablet5 MG
Tablet, film coatedOral160 mg
Tablet, film coatedOral80 mg
CapsuleOral
Tablet7.5 MG
TabletOral10 mg/1
TabletOral2.5 mg/1
TabletOral5 mg/1
TabletOral5 mg
TabletOral13.88 mg
Tablet, effervescent1.25 mg
Tablet, effervescent2.5 mg
Tablet, effervescent5 mg
TabletOral2.5 mg
TabletOral10 mg
Capsule, coatedOral10 mg
TabletOral150 mg
Capsule, coatedOral5 mg
Capsule, coatedOral2.5 mg
TabletOral80 mg
Tablet, coatedOral20 mg
Tablet, coatedOral40 mg
Tablet, coatedOral2.5 mg
Tablet10 mg/1
Tablet5 mg/1
Capsule, coatedOral6.934 mg
TabletOral4 MG
CapsuleOral16 mg/1
CapsuleOral8 mg/1
Tablet, film coatedOral13.87 mg
Tablet, film coatedOral6.93 mg
Tablet16 mg/1
Tablet8 mg/1
CapsuleOral16 MG
CapsuleOral8 MG
TabletOral16 mg
TabletOral32 mg
TabletOral8 mg
Tablet, coated5 mg
TabletOral160 mg
Tablet, coatedOral160 mg
Tablet, coatedOral320 mg
Tablet, film coatedOral
Tablet, film coatedOral160 mg/1
Tablet, film coatedOral5 MG/160MG
Tablet, film coatedOral80 mg/1
TabletOral14 mg
TabletOral3.5 mg
TabletOral7 mg
Tablet, film coatedOral320 mg
Tablet, film coatedOral10 mg
Tablet, film coatedOral5 mg
Tablet, effervescent10 mg
KitOral
Tablet, film coatedOral
Tablet, film coatedOral150 mg
Tablet, film coatedOral300 mg
Tablet, coatedOral150 mg
Tablet, coatedOral300 mg
SuspensionOral1 mg/1mL
Tablet, effervescentOral10 mg
Tablet, effervescentOral5 mg
Tablet, film coatedOral100 mg
Tablet, film coatedOral50 mg
TabletOral
Tablet, delayed releaseOral5 mg
Tablet, delayed releaseOral1.5 mg
Tablet, coated2.5 mg
Tablet, coated10 mg
Tablet, orally disintegratingOral10 mg
Tablet, orally disintegratingOral5 mg
Tablet, film coatedOral20 mg
Tablet, film coatedOral40 mg
Tablet, coatedOral5 mg
Tablet, film coatedOral13.88 mg
SolutionOral
CapsuleOral10 mg
CapsuleOral2.5 mg
CapsuleOral5 mg
Tablet, coated20 mg
CapsuleOral20 MG
Tablet2.5 mg
Tablet, film coated20 mg
Tablet, film coated40 mg
Tablet
Tablet16 mg
Tablet32 mg
CapsuleOral30 mg
TabletOral
Tablet, multilayerOral
Tablet40 mg
Tablet80 mg
Tablet, coatedOral13.86857 mg
Tablet, coatedOral6.93429 mg
Capsule, liquid filledOral10 mg
Capsule, liquid filledOral5 mg
Tablet3.5 mg
Tablet7 mg
Prices
Unit descriptionCostUnit
Amlodipine besylate powder9.99USD g
Lotrel 10-40 mg capsule5.21USD capsule
Lotrel 10-20 mg capsule4.8USD capsule
Lotrel 5-40 mg capsule4.37USD capsule
Lotrel 5-20 mg capsule4.13USD capsule
Lotrel 5-10 mg capsule3.91USD capsule
Lotrel 2.5-10 mg capsule3.83USD capsule
Norvasc 10 mg tablet3.16USD tablet
Amlodipine besylate 10 mg tablet2.42USD tablet
Norvasc 2.5 mg tablet2.36USD tablet
Norvasc 5 mg tablet2.36USD tablet
Norvasc 10 mg Tablet2.14USD tablet
Amlodipine besylate 2.5 mg tablet1.76USD tablet
Amlodipine besylate 5 mg tablet1.76USD tablet
Norvasc 5 mg Tablet1.44USD tablet
Amlodipine 10 mg Tablet1.03USD tablet
Apo-Amlodipine 10 mg Tablet1.03USD tablet
Co Amlodipine 10 mg Tablet1.03USD tablet
Gd-Amlodipine 10 mg Tablet1.03USD tablet
Jamp-Amlodipine 10 mg Tablet1.03USD tablet
Mylan-Amlodipine 10 mg Tablet1.03USD tablet
Novo-Amlodipine 10 mg Tablet1.03USD tablet
Phl-Amlodipine 10 mg Tablet1.03USD tablet
Pms-Amlodipine 10 mg Tablet1.03USD tablet
Ran-Amlodipine 10 mg Tablet1.03USD tablet
Ratio-Amlodipine 10 mg Tablet1.03USD tablet
Sandoz Amlodipine 10 mg Tablet1.03USD tablet
Amlodipine 5 mg Tablet0.7USD tablet
Apo-Amlodipine 5 mg Tablet0.7USD tablet
Co Amlodipine 5 mg Tablet0.7USD tablet
Gd-Amlodipine 5 mg Tablet0.7USD tablet
Jamp-Amlodipine 5 mg Tablet0.7USD tablet
Mylan-Amlodipine 5 mg Tablet0.7USD tablet
Novo-Amlodipine 5 mg Tablet0.7USD tablet
Phl-Amlodipine 5 mg Tablet0.7USD tablet
Pms-Amlodipine 5 mg Tablet0.7USD tablet
Ran-Amlodipine 5 mg Tablet0.7USD tablet
Ratio-Amlodipine 5 mg Tablet0.7USD tablet
Sandoz Amlodipine 5 mg Tablet0.7USD tablet
Phl-Amlodipine 2.5 mg Tablet0.35USD tablet
Pms-Amlodipine 2.5 mg Tablet0.35USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)Region
CA2170278No1999-08-032014-08-10Canada flag
US6162802No2000-12-192017-12-19US flag
US5969156Yes1999-10-192017-01-08US flag
US6294197Yes2001-09-252017-12-18US flag
US5559111Yes1996-09-242019-01-21US flag
US6395728No2002-05-282019-07-08US flag
US6828339No2004-12-072022-11-20US flag
US5616599Yes1997-04-012016-10-25US flag
US6455574No2002-09-242018-08-11US flag
US8101599No2012-01-242023-05-16US flag
US8475839Yes2013-07-022023-11-16US flag
US8613949No2013-12-242029-12-21US flag
US8618174No2013-12-312021-11-15US flag
US8183295No2012-05-222023-05-16US flag
US7846961No2010-12-072029-10-05US flag
US6696481No2004-02-242023-04-15US flag
US9662315No2017-05-302030-02-28US flag
US10350171No2019-07-162038-06-14US flag
US10695329No2017-10-162037-10-16US flag
Additional Data Available
  • Filed On
    Filed On

    The date on which a patent was filed with the relevant government.

    Learn more

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)199-201https://www.chemicalbook.com/ChemicalProductProperty_US_CB4127875.aspx
boiling point (°C)527.2https://www.lookchem.com/Amlodipine-besylate/
water solubilityslightly soluble in waterFDA label
logP3.00AUSTIN,RP ET AL. (1995)
Predicted Properties
PropertyValueSource
Water Solubility0.0074 mg/mLALOGPS
logP2.22ALOGPS
logP1.64ChemAxon
logS-4.7ALOGPS
pKa (Strongest Acidic)19.12ChemAxon
pKa (Strongest Basic)9.45ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area99.88 Å2ChemAxon
Rotatable Bond Count10ChemAxon
Refractivity108.64 m3·mol-1ChemAxon
Polarizability42.31 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET Features
PropertyValueProbability
Human Intestinal Absorption+0.9479
Blood Brain Barrier-0.7744
Caco-2 permeable-0.5468
P-glycoprotein substrateSubstrate0.9102
P-glycoprotein inhibitor IInhibitor0.8564
P-glycoprotein inhibitor IINon-inhibitor0.8473
Renal organic cation transporterNon-inhibitor0.803
CYP450 2C9 substrateNon-substrate0.8627
CYP450 2D6 substrateNon-substrate0.9116
CYP450 3A4 substrateSubstrate0.6967
CYP450 1A2 substrateInhibitor0.538
CYP450 2C9 inhibitorInhibitor0.514
CYP450 2D6 inhibitorNon-inhibitor0.7626
CYP450 2C19 inhibitorInhibitor0.5871
CYP450 3A4 inhibitorInhibitor0.8608
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.6642
Ames testNon AMES toxic0.7605
CarcinogenicityNon-carcinogens0.8568
BiodegradationNot ready biodegradable0.9791
Rat acute toxicity2.5396 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.8302
hERG inhibition (predictor II)Inhibitor0.8411
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available
LC-MS/MS Spectrum - LC-ESI-QTOF , positiveLC-MS/MSsplash10-0a4u-0192000000-988fbef9dd83defbfbe0
MS/MS Spectrum - , positiveLC-MS/MSsplash10-002o-1392000000-3e9bc5dcf61b0f4cae6a
1H NMR Spectrum1D NMRNot Applicable
[1H,13C] 2D NMR Spectrum2D NMRNot Applicable

Targets

Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
General Function
Voltage-gated calcium channel activity
Specific Function
Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hor...
Gene Name
CACNA1C
Uniprot ID
Q13936
Uniprot Name
Voltage-dependent L-type calcium channel subunit alpha-1C
Molecular Weight
248974.1 Da
References
  1. Bodi I, Mikala G, Koch SE, Akhter SA, Schwartz A: The L-type calcium channel in the heart: the beat goes on. J Clin Invest. 2005 Dec;115(12):3306-17. doi: 10.1172/JCI27167. [PubMed:16322774]
  2. Tang L, Gamal El-Din TM, Swanson TM, Pryde DC, Scheuer T, Zheng N, Catterall WA: Structural basis for inhibition of a voltage-gated Ca(2+) channel by Ca(2+) antagonist drugs. Nature. 2016 Sep 1;537(7618):117-121. doi: 10.1038/nature19102. Epub 2016 Aug 24. [PubMed:27556947]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Voltage-gated calcium channel activity
Specific Function
Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hor...
Gene Name
CACNA1B
Uniprot ID
Q00975
Uniprot Name
Voltage-dependent N-type calcium channel subunit alpha-1B
Molecular Weight
262493.84 Da
References
  1. Furukawa T, Nukada T, Suzuki K, Fujita Y, Mori Y, Nishimura M, Yamanaka M: Voltage and pH dependent block of cloned N-type Ca2+ channels by amlodipine. Br J Pharmacol. 1997 Jul;121(6):1136-40. [PubMed:9249249]
  2. Furukawa T, Yamakawa T, Midera T, Sagawa T, Mori Y, Nukada T: Selectivities of dihydropyridine derivatives in blocking Ca(2+) channel subtypes expressed in Xenopus oocytes. J Pharmacol Exp Ther. 1999 Nov;291(2):464-73. [PubMed:10525060]
  3. Miyashita Y, Furukawa T, Kamegaya E, Yoshii M, Nukada T: A region of N-type Ca(2+) channel critical for blockade by the dihydropyridine amlodipine. Eur J Pharmacol. 2010 Apr 25;632(1-3):14-22. doi: 10.1016/j.ejphar.2010.01.006. Epub 2010 Jan 22. [PubMed:20097194]
  4. Murakami M, Nakagawasai O, Fujii S, Kameyama K, Murakami S, Hozumi S, Esashi A, Taniguchi R, Yanagisawa T, Tan-no K, Tadano T, Kitamura K, Kisara K: Antinociceptive action of amlodipine blocking N-type Ca2+ channels at the primary afferent neurons in mice. Eur J Pharmacol. 2001 May 11;419(2-3):175-81. [PubMed:11426839]
  5. Ogihara T, Kano T, Kakinuma C: Evaluation of the inhibitory effect of dihydropyridines on N-type calcium channel by virtual three-dimensional pharmacophore modeling. Arzneimittelforschung. 2009;59(6):283-8. doi: 10.1055/s-0031-1296398. [PubMed:19634509]
  6. Qu YL, Sugiyama K, Ohnuki T, Hattori K, Watanabe K, Nagatomo T: Comparison of binding affinities of omega-conotoxin and amlodipine to N-type Ca2+ channels in rat brain. Zhongguo Yao Li Xue Bao. 1998 Mar;19(2):97-100. [PubMed:10374627]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Voltage-gated calcium channel activity
Specific Function
The beta subunit of voltage-dependent calcium channels contributes to the function of the calcium channel by increasing peak calcium current, shifting the voltage dependencies of activation and ina...
Gene Name
CACNB1
Uniprot ID
Q02641
Uniprot Name
Voltage-dependent L-type calcium channel subunit beta-1
Molecular Weight
65712.995 Da
References
  1. Furukawa T, Nukada T, Suzuki K, Fujita Y, Mori Y, Nishimura M, Yamanaka M: Voltage and pH dependent block of cloned N-type Ca2+ channels by amlodipine. Br J Pharmacol. 1997 Jul;121(6):1136-40. [PubMed:9249249]
  2. Furukawa T, Yamakawa T, Midera T, Sagawa T, Mori Y, Nukada T: Selectivities of dihydropyridine derivatives in blocking Ca(2+) channel subtypes expressed in Xenopus oocytes. J Pharmacol Exp Ther. 1999 Nov;291(2):464-73. [PubMed:10525060]
  3. Miyashita Y, Furukawa T, Kamegaya E, Yoshii M, Nukada T: A region of N-type Ca(2+) channel critical for blockade by the dihydropyridine amlodipine. Eur J Pharmacol. 2010 Apr 25;632(1-3):14-22. doi: 10.1016/j.ejphar.2010.01.006. Epub 2010 Jan 22. [PubMed:20097194]
  4. Murakami M, Nakagawasai O, Fujii S, Kameyama K, Murakami S, Hozumi S, Esashi A, Taniguchi R, Yanagisawa T, Tan-no K, Tadano T, Kitamura K, Kisara K: Antinociceptive action of amlodipine blocking N-type Ca2+ channels at the primary afferent neurons in mice. Eur J Pharmacol. 2001 May 11;419(2-3):175-81. [PubMed:11426839]
  5. Ogihara T, Kano T, Kakinuma C: Evaluation of the inhibitory effect of dihydropyridines on N-type calcium channel by virtual three-dimensional pharmacophore modeling. Arzneimittelforschung. 2009;59(6):283-8. doi: 10.1055/s-0031-1296398. [PubMed:19634509]
  6. Qu YL, Sugiyama K, Ohnuki T, Hattori K, Watanabe K, Nagatomo T: Comparison of binding affinities of omega-conotoxin and amlodipine to N-type Ca2+ channels in rat brain. Zhongguo Yao Li Xue Bao. 1998 Mar;19(2):97-100. [PubMed:10374627]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Voltage-gated ion channel activity
Specific Function
The alpha-2/delta subunit of voltage-dependent calcium channels regulates calcium current density and activation/inactivation kinetics of the calcium channel. Acts as a regulatory subunit for P/Q-t...
Gene Name
CACNA2D3
Uniprot ID
Q8IZS8
Uniprot Name
Voltage-dependent calcium channel subunit alpha-2/delta-3
Molecular Weight
123010.22 Da
References
  1. Furukawa T, Nukada T, Suzuki K, Fujita Y, Mori Y, Nishimura M, Yamanaka M: Voltage and pH dependent block of cloned N-type Ca2+ channels by amlodipine. Br J Pharmacol. 1997 Jul;121(6):1136-40. [PubMed:9249249]
  2. Furukawa T, Yamakawa T, Midera T, Sagawa T, Mori Y, Nukada T: Selectivities of dihydropyridine derivatives in blocking Ca(2+) channel subtypes expressed in Xenopus oocytes. J Pharmacol Exp Ther. 1999 Nov;291(2):464-73. [PubMed:10525060]
  3. Miyashita Y, Furukawa T, Kamegaya E, Yoshii M, Nukada T: A region of N-type Ca(2+) channel critical for blockade by the dihydropyridine amlodipine. Eur J Pharmacol. 2010 Apr 25;632(1-3):14-22. doi: 10.1016/j.ejphar.2010.01.006. Epub 2010 Jan 22. [PubMed:20097194]
  4. Murakami M, Nakagawasai O, Fujii S, Kameyama K, Murakami S, Hozumi S, Esashi A, Taniguchi R, Yanagisawa T, Tan-no K, Tadano T, Kitamura K, Kisara K: Antinociceptive action of amlodipine blocking N-type Ca2+ channels at the primary afferent neurons in mice. Eur J Pharmacol. 2001 May 11;419(2-3):175-81. [PubMed:11426839]
  5. Ogihara T, Kano T, Kakinuma C: Evaluation of the inhibitory effect of dihydropyridines on N-type calcium channel by virtual three-dimensional pharmacophore modeling. Arzneimittelforschung. 2009;59(6):283-8. doi: 10.1055/s-0031-1296398. [PubMed:19634509]
  6. Qu YL, Sugiyama K, Ohnuki T, Hattori K, Watanabe K, Nagatomo T: Comparison of binding affinities of omega-conotoxin and amlodipine to N-type Ca2+ channels in rat brain. Zhongguo Yao Li Xue Bao. 1998 Mar;19(2):97-100. [PubMed:10374627]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Zinc ion binding
Specific Function
Reversible hydration of carbon dioxide. Can hydrates cyanamide to urea.
Gene Name
CA1
Uniprot ID
P00915
Uniprot Name
Carbonic anhydrase 1
Molecular Weight
28870.0 Da
References
  1. Puscas I, Gilau L, Coltau M, Pasca R, Domuta G, Baican M, Hecht A: Hypotensive effect of calcium channel blockers is parallel with carbonic anhydrase I inhibition. Clin Pharmacol Ther. 2000 Oct;68(4):443-9. [PubMed:11061585]
  2. Puscas L, Gilau L, Coltau M, Pasca R, Domuta G, Baican M, Hecht A: Calcium channel blockers reduce blood pressure in part by inhibiting vascular smooth muscle carbonic anhydrase I. Cardiovasc Drugs Ther. 2000 Oct;14(5):523-8. [PubMed:11101200]
  3. Puscas I, Coltau M, Baican M, Pasca R, Domuta G, Hecht A: Vasoconstrictive drugs increase carbonic anhydrase I in vascular smooth muscle while vasodilating drugs reduce the activity of this isozyme by a direct mechanism of action. Drugs Exp Clin Res. 2001;27(2):53-60. [PubMed:11392054]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Sphingomyelin phosphodiesterase activity
Specific Function
Converts sphingomyelin to ceramide. Also has phospholipase C activities toward 1,2-diacylglycerolphosphocholine and 1,2-diacylglycerolphosphoglycerol. Isoform 2 and isoform 3 have lost catalytic ac...
Gene Name
SMPD1
Uniprot ID
P17405
Uniprot Name
Sphingomyelin phosphodiesterase
Molecular Weight
69751.3 Da
References
  1. Kornhuber J, Muehlbacher M, Trapp S, Pechmann S, Friedl A, Reichel M, Muhle C, Terfloth L, Groemer TW, Spitzer GM, Liedl KR, Gulbins E, Tripal P: Identification of novel functional inhibitors of acid sphingomyelinase. PLoS One. 2011;6(8):e23852. doi: 10.1371/journal.pone.0023852. Epub 2011 Aug 31. [PubMed:21909365]
  2. Identification of New Functional Inhibitors of Acid Sphingomyelinase Using a Structure-Property-Activity Relation Model [File]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Inhibitor
General Function
Voltage-gated calcium channel activity
Specific Function
Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hor...
Gene Name
CACNA1I
Uniprot ID
Q9P0X4
Uniprot Name
Voltage-dependent T-type calcium channel subunit alpha-1I
Molecular Weight
245100.8 Da
References
  1. Lin M, Aladejebi O, Hockerman GH: Distinct properties of amlodipine and nicardipine block of the voltage-dependent Ca2+ channels Cav1.2 and Cav2.1 and the mutant channels Cav1.2/dihydropyridine insensitive and Cav2.1/dihydropyridine sensitive. Eur J Pharmacol. 2011 Nov 16;670(1):105-13. doi: 10.1016/j.ejphar.2011.08.005. Epub 2011 Sep 2. [PubMed:21910984]
  2. Striessnig J, Ortner NJ, Pinggera A: Pharmacology of L-type Calcium Channels: Novel Drugs for Old Targets? Curr Mol Pharmacol. 2015;8(2):110-22. [PubMed:25966690]
  3. Inoue Y, Hisatome I, Tsuboi M, Ahmmed GU, Yatsuhashi T, Uchida K, Yamanouchi Y, Santo Y, Miake J, Tanaka Y, Hamada T, Watanabe M, Igawa O, Yoshida A, Shigemasa C, Makita N, Sato R: Effects of amlodipine on native cardiac Na+ channels and cloned alpha-subunits of cardiac Na+ channels. Arzneimittelforschung. 1999 May;49(5):394-7. doi: 10.1055/s-0031-1300433. [PubMed:10367100]
  4. Ozawa Y, Hayashi K, Kobori H: New Generation Calcium Channel Blockers in Hypertensive Treatment. Curr Hypertens Rev. 2006 May 1;2(2):103-111. doi: 10.2174/157340206776877370. [PubMed:19823601]
Kind
Protein group
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Voltage-sensitive calcium channels (VSCC) mediate the entry of calcium ions into excitable cells and are also involved in a variety of calcium-dependent processes, including muscle contraction, hormone or neurotransmitter release, gene expression, cell motility, cell division and cell death. The isoform alpha-1B gives rise to N-type calcium currents.
Specific Function
Voltage-gated calcium channel activity

Components:
References
  1. Miyashita Y, Furukawa T, Kamegaya E, Yoshii M, Nukada T: A region of N-type Ca(2+) channel critical for blockade by the dihydropyridine amlodipine. Eur J Pharmacol. 2010 Apr 25;632(1-3):14-22. doi: 10.1016/j.ejphar.2010.01.006. Epub 2010 Jan 22. [PubMed:20097194]
  2. Godfraind T: Discovery and Development of Calcium Channel Blockers. Front Pharmacol. 2017 May 29;8:286. doi: 10.3389/fphar.2017.00286. eCollection 2017. [PubMed:28611661]
  3. Furukawa T, Nukada T, Suzuki K, Fujita Y, Mori Y, Nishimura M, Yamanaka M: Voltage and pH dependent block of cloned N-type Ca2+ channels by amlodipine. Br J Pharmacol. 1997 Jul;121(6):1136-40. [PubMed:9249249]

Enzymes

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. Katoh M, Nakajima M, Shimada N, Yamazaki H, Yokoi T: Inhibition of human cytochrome P450 enzymes by 1,4-dihydropyridine calcium antagonists: prediction of in vivo drug-drug interactions. Eur J Clin Pharmacol. 2000 Feb-Mar;55(11-12):843-52. [PubMed:10805063]
  2. Zhu Y, Wang F, Li Q, Zhu M, Du A, Tang W, Chen W: Amlodipine metabolism in human liver microsomes and roles of CYP3A4/5 in the dihydropyridine dehydrogenation. Drug Metab Dispos. 2014 Feb;42(2):245-9. doi: 10.1124/dmd.113.055400. Epub 2013 Dec 3. [PubMed:24301608]
  3. Flockhart Table of Drug Interactions [Link]
  4. Amlodipine FDA label [File]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
Curator comments
Limited in vitro data support this enzyme action.
General Function
Vitamin d 24-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP1A1
Uniprot ID
P04798
Uniprot Name
Cytochrome P450 1A1
Molecular Weight
58164.815 Da
References
  1. Katoh M, Nakajima M, Shimada N, Yamazaki H, Yokoi T: Inhibition of human cytochrome P450 enzymes by 1,4-dihydropyridine calcium antagonists: prediction of in vivo drug-drug interactions. Eur J Clin Pharmacol. 2000 Feb-Mar;55(11-12):843-52. [PubMed:10805063]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
Curator comments
Data supporting this enzyme action are limited to in vitro studies in addition studies performed with rabbits.
General Function
Steroid hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP2B6
Uniprot ID
P20813
Uniprot Name
Cytochrome P450 2B6
Molecular Weight
56277.81 Da
References
  1. Katoh M, Nakajima M, Shimada N, Yamazaki H, Yokoi T: Inhibition of human cytochrome P450 enzymes by 1,4-dihydropyridine calcium antagonists: prediction of in vivo drug-drug interactions. Eur J Clin Pharmacol. 2000 Feb-Mar;55(11-12):843-52. [PubMed:10805063]
  2. Shah MB, Wilderman PR, Pascual J, Zhang Q, Stout CD, Halpert JR: Conformational adaptation of human cytochrome P450 2B6 and rabbit cytochrome P450 2B4 revealed upon binding multiple amlodipine molecules. Biochemistry. 2012 Sep 18;51(37):7225-38. doi: 10.1021/bi300894z. Epub 2012 Sep 4. [PubMed:22909231]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
Curator comments
There are contradictory data available on this enzyme action. Some studies suggest this drug is a CYP3A5 substrate, while others suggest it does not have a role in amlodipine metabolism.
General Function
Oxygen binding
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP3A5
Uniprot ID
P20815
Uniprot Name
Cytochrome P450 3A5
Molecular Weight
57108.065 Da
References
  1. Zhu Y, Wang F, Li Q, Zhu M, Du A, Tang W, Chen W: Amlodipine metabolism in human liver microsomes and roles of CYP3A4/5 in the dihydropyridine dehydrogenation. Drug Metab Dispos. 2014 Feb;42(2):245-9. doi: 10.1124/dmd.113.055400. Epub 2013 Dec 3. [PubMed:24301608]
  2. Bhatnagar V, Garcia EP, O'Connor DT, Brophy VH, Alcaraz J, Richard E, Bakris GL, Middleton JP, Norris KC, Wright J, Hiremath L, Contreras G, Appel LJ, Lipkowitz MS: CYP3A4 and CYP3A5 polymorphisms and blood pressure response to amlodipine among African-American men and women with early hypertensive renal disease. Am J Nephrol. 2010;31(2):95-103. doi: 10.1159/000258688. Epub 2009 Nov 12. [PubMed:19907160]
  3. Lu Y, Zhong H, Tang Q, Huang Z, Jing N, Smith J, Miao R, Li Y, Yuan H: Construction and verification of CYP3A5 gene polymorphisms using a Saccharomyces cerevisiae expression system to predict drug metabolism. Mol Med Rep. 2017 Apr;15(4):1593-1600. doi: 10.3892/mmr.2017.6214. Epub 2017 Feb 17. [PubMed:28259948]
  4. Zhang YP, Zuo XC, Huang ZJ, Cai JJ, Wen J, Duan DD, Yuan H: CYP3A5 polymorphism, amlodipine and hypertension. J Hum Hypertens. 2014 Mar;28(3):145-9. doi: 10.1038/jhh.2013.67. Epub 2013 Jul 18. [PubMed:23863802]
  5. Flockhart Table of Drug Interactions [Link]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP2C8
Uniprot ID
P10632
Uniprot Name
Cytochrome P450 2C8
Molecular Weight
55824.275 Da
References
  1. Floyd JS, Kaspera R, Marciante KD, Weiss NS, Heckbert SR, Lumley T, Wiggins KL, Tamraz B, Kwok PY, Totah RA, Psaty BM: A screening study of drug-drug interactions in cerivastatin users: an adverse effect of clopidogrel. Clin Pharmacol Ther. 2012 May;91(5):896-904. doi: 10.1038/clpt.2011.295. Epub 2012 Mar 14. [PubMed:22419147]
  2. Backman JT, Filppula AM, Niemi M, Neuvonen PJ: Role of Cytochrome P450 2C8 in Drug Metabolism and Interactions. Pharmacol Rev. 2016 Jan;68(1):168-241. doi: 10.1124/pr.115.011411. [PubMed:26721703]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
Curator comments
Data of this enzyme action are limited and are based on results of in vitro studies.
General Function
Steroid hydroxylase activity
Specific Function
Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic...
Gene Name
CYP2D6
Uniprot ID
P10635
Uniprot Name
Cytochrome P450 2D6
Molecular Weight
55768.94 Da
References
  1. Augustin M, Schoretsanitis G, Grunder G, Haen E, Paulzen M: How to Treat Hypertension in Venlafaxine-Medicated Patients-Pharmacokinetic Considerations in Prescribing Amlodipine and Ramipril. J Clin Psychopharmacol. 2018 Oct;38(5):498-501. doi: 10.1097/JCP.0000000000000929. [PubMed:30102628]
  2. Ma B, Prueksaritanont T, Lin JH: Drug interactions with calcium channel blockers: possible involvement of metabolite-intermediate complexation with CYP3A. Drug Metab Dispos. 2000 Feb;28(2):125-30. [PubMed:10640508]

Transporters

Details
1. P-glycoprotein 1
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Xenobiotic-transporting atpase activity
Specific Function
Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells.
Gene Name
ABCB1
Uniprot ID
P08183
Uniprot Name
Multidrug resistance protein 1
Molecular Weight
141477.255 Da
References
  1. Katoh M, Nakajima M, Yamazaki H, Yokoi T: Inhibitory potencies of 1,4-dihydropyridine calcium antagonists to P-glycoprotein-mediated transport: comparison with the effects on CYP3A4. Pharm Res. 2000 Oct;17(10):1189-97. [PubMed:11145223]
  2. Darvari R, Boroujerdi M: Concentration dependency of modulatory effect of amlodipine on P-glycoprotein efflux activity of doxorubicin--a comparison with tamoxifen. J Pharm Pharmacol. 2004 Aug;56(8):985-91. doi: 10.1211/0022357043941. [PubMed:15285842]
  3. Kuzuya T, Kobayashi T, Moriyama N, Nagasaka T, Yokoyama I, Uchida K, Nakao A, Nabeshima T: Amlodipine, but not MDR1 polymorphisms, alters the pharmacokinetics of cyclosporine A in Japanese kidney transplant recipients. Transplantation. 2003 Sep 15;76(5):865-8. doi: 10.1097/01.TP.0000084873.20157.67. [PubMed:14501869]
  4. Kim KA, Park PW, Park JY: Effect of ABCB1 (MDR1) haplotypes derived from G2677T/C3435T on the pharmacokinetics of amlodipine in healthy subjects. Br J Clin Pharmacol. 2007 Jan;63(1):53-8. doi: 10.1111/j.1365-2125.2006.02733.x. Epub 2006 Jul 21. [PubMed:16869811]

Drug created on June 13, 2005 07:24 / Updated on October 25, 2020 09:16

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