Identification

Name
Amlodipine
Accession Number
DB00381  (APRD00520)
Type
Small Molecule
Groups
Approved
Description

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.

Structure
Thumb
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
Product Ingredients
IngredientUNIICASInChI Key
Amlodipine besylate864V2Q084H111470-99-6ZPBWCRDSRKPIDG-UHFFFAOYSA-N
Amlodipine maleateCQ27G2BZJM88150-47-4TZNOWAJJWCGILX-BTJKTKAUSA-N
Amlodipine mesylate291Y33EZHA246852-12-0MUVFCHUBATVFPP-UHFFFAOYSA-N
Product Images
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Act AmlodipineTablet5 mgOralActavis Pharma Company2009-07-10Not applicableCanada
Act AmlodipineTablet2.5 mgOralActavis Pharma Company2010-03-02Not applicableCanada
Act AmlodipineTablet10 mgOralActavis Pharma Company2009-07-10Not applicableCanada
AmlodipineTablet5 mgOralSivem Pharmaceuticals Ulc2012-06-12Not applicableCanada
AmlodipineTablet10 mgOralSanis Health Inc2009-10-22Not applicableCanada
AmlodipineTablet2.5 mgOralMeliapharm Inc2011-04-082014-06-25Canada
AmlodipineTablet10 mgOralJamp Pharma Corporation2014-09-04Not applicableCanada
AmlodipineTablet2.5 mgOralPro Doc Limitee2009-07-22Not applicableCanada
AmlodipineTablet2.5 mgOralActavis Pharma CompanyNot applicableNot applicableCanada
AmlodipineTablet10 mgOralMeliapharm Inc2011-04-082014-06-25Canada
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Accel-amlodipineTablet5 mgOralAccel Pharma Inc2010-03-052016-10-19Canada
Accel-amlodipineTablet10 mgOralAccel Pharma Inc2010-03-052016-10-19Canada
Accel-amlodipineTablet2.5 mgOralAccel Pharma IncNot applicableNot applicableCanada
Ag-amlodipineTablet5 mgOralAngita Pharma Inc.2014-09-25Not applicableCanada
Ag-amlodipineTablet2.5 mgOralAngita Pharma Inc.Not applicableNot applicableCanada
Ag-amlodipineTablet10 mgOralAngita Pharma Inc.2014-09-25Not applicableCanada
AmlodipineTablet5 mg/1OralMacleods Pharmaceuticals Limited2012-04-13Not applicableUs
AmlodipineTablet10 mg/1OralRemedy Repack2011-04-132011-04-14Us
AmlodipineTablet10 mg/1OralMacleods Pharmaceuticals Limited2012-04-13Not applicableUs
AmlodipineTablet10 mg/1OralState of Florida DOH Central Pharmacy2013-01-01Not applicableUs
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
AmlobenzAmlodipine besylate (10 mg/1) + Benazepril hydrochloride (20 mg/1)CapsuleOralRebel Distributors2010-04-19Not applicableUs55111 0341 01 nlmimage10 c238e107
AmlobenzAmlodipine besylate (5 mg/1) + Benazepril hydrochloride (10 mg/1)CapsuleOralRebel Distributors2010-04-19Not applicableUs55111 0339 01 nlmimage10 6d03b6bd
Amlodipine and Benazepril HydrochlorideAmlodipine besylate (5 mg/1) + Benazepril hydrochloride (40 mg/1)CapsuleOralbryant ranch prepack2012-09-05Not applicableUs
Amlodipine and Benazepril HydrochlorideAmlodipine besylate (5 mg/1) + Benazepril hydrochloride (10 mg/1)CapsuleOralAurobindo Pharma2012-09-05Not applicableUs65862 0583 01 nlmimage10 6039b03d
Amlodipine and Benazepril HydrochlorideAmlodipine besylate (10 mg/1) + Benazepril hydrochloride (40 mg/1)CapsuleOralNucare Pharmaceuticals,inc.2012-09-05Not applicableUs
Amlodipine and Benazepril HydrochlorideAmlodipine besylate (2.5 mg/1) + Benazepril hydrochloride (10 mg/1)CapsuleOralTeva Pharmaceuticals USA, Inc.2007-05-18Not applicableUs00093 7370 01 nlmimage10 f026f807
Amlodipine and Benazepril HydrochlorideAmlodipine besylate (5 mg/1) + Benazepril hydrochloride (40 mg/1)CapsuleOralNucare Pharmaceuticals,inc.2012-09-05Not applicableUs
Amlodipine and Benazepril HydrochlorideAmlodipine besylate (10 mg/1) + Benazepril hydrochloride (40 mg/1)CapsuleOralMylan Pharmaceuticals2012-02-202019-01-31Us
Amlodipine and Benazepril HydrochlorideAmlodipine besylate (5 mg/1) + Benazepril hydrochloride (20 mg/1)CapsuleOralMylan Pharmaceuticals2012-02-202019-01-31Us0378 689720180913 8702 199ac6q
Amlodipine and Benazepril HydrochlorideAmlodipine besylate (5 mg/1) + Benazepril hydrochloride (20 mg/1)CapsuleOralA-S Medication Solutions2012-09-05Not applicableUs50090 104220180907 15195 1228t51
Unapproved/Other Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
AmlodipineAmlodipine besylate (10 mg/1)TabletOralCaraco Pharmaceutical Laboratories, Ltd.2008-12-15Not applicableUs
AmlodipineAmlodipine besylate (5 mg/1)TabletOralCaraco Pharmaceutical Laboratories, Ltd.2008-12-15Not applicableUs
AmlodipineAmlodipine besylate (2.5 mg/1)TabletOralCaraco Pharmaceutical Laboratories, Ltd.2008-12-15Not applicableUs
Amlodipine BesylateAmlodipine besylate (10 mg/1)TabletOralSynthon Pharmaceuticals, Inc.2008-01-23Not applicableUs
Amlodipine BesylateAmlodipine besylate (2.5 mg/1)TabletOralSynthon Pharmaceuticals, Inc.2008-01-23Not applicableUs
Amlodipine BesylateAmlodipine besylate (2.5 mg/1)TabletOralKali Laboratories, Inc., A Wholly Owned Subsidiary of Par Pharmaceutical Companies2007-08-03Not applicableUs
Amlodipine BesylateAmlodipine besylate (10 mg/1)TabletOralKali Laboratories, Inc., A Wholly Owned Subsidiary of Par Pharmaceutical Companies2007-08-03Not applicableUs
Amlodipine BesylateAmlodipine besylate (5 mg/1)TabletOralSynthon Pharmaceuticals, Inc.2008-01-23Not applicableUs
Amlodipine BesylateAmlodipine besylate (5 mg/1)TabletOralKali Laboratories, Inc., A Wholly Owned Subsidiary of Par Pharmaceutical Companies2007-08-03Not applicableUs
HypertenipineAmlodipine besylate (2.5 mg/1) + L-Arginine (90 mg/1)KitPhysician Therapeutics Llc2011-07-07Not applicableUs
International/Other Brands
Aforbes (Merck) / Agen (Zentiva) / Aken (Kendrick Farmaceutica) / Amcard (Apex Pharma Ltd) / Amdepin (Cadila Pharmaceuticals) / Amdipin (Laboratorios Lafrancol) / 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) / 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)
Categories
UNII
1J444QC288
CAS number
88150-42-9
Weight
Average: 408.876
Monoisotopic: 408.145199627
Chemical Formula
C20H25ClN2O5
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

Pharmacology

Indication

For the treatment of hypertension and chronic stable angina.

Associated Conditions
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.

TargetActionsOrganism
AVoltage-dependent L-type calcium channel subunit alpha-1C
inhibitor
Human
AVoltage-dependent calcium channel subunit alpha-2/delta-1
inhibitor
Human
AVoltage-dependent L-type calcium channel subunit beta-2
inhibitor
Human
AVoltage-dependent L-type calcium channel subunit alpha-1D
inhibitor
Human
AVoltage-dependent L-type calcium channel subunit alpha-1S
inhibitor
Human
UVoltage-dependent N-type calcium channel subunit alpha-1B
inhibitor
Human
UVoltage-dependent calcium channel subunit alpha-2/delta-3
inhibitor
Human
UVoltage-gated calcium channel beta 1 subunit splice variant CavB1d
inhibitor
Human
UCarbonic anhydrase 1
inhibitor
Human
USphingomyelin phosphodiesterase
inhibitor
Human
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
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
DrugInteraction
AbacavirAmlodipine may decrease the excretion rate of Abacavir which could result in a higher serum level.
AbafunginThe therapeutic efficacy of Abafungin can be increased when used in combination with Amlodipine.
AbemaciclibThe serum concentration of Abemaciclib can be increased when it is combined with Amlodipine.
AcarboseAcarbose may decrease the excretion rate of Amlodipine which could result in a higher serum level.
AcebutololThe risk or severity of bradycardia can be increased when Amlodipine is combined with Acebutolol.
AceclofenacThe therapeutic efficacy of Amlodipine can be decreased when used in combination with Aceclofenac.
AcemetacinThe therapeutic efficacy of Amlodipine can be decreased when used in combination with Acemetacin.
AcepromazineThe risk or severity of hypotension can be increased when Acepromazine is combined with Amlodipine.
AcetaminophenAcetaminophen may decrease the excretion rate of Amlodipine which could result in a higher serum level.
AcetarsolAmlodipine may decrease the excretion rate of Acetarsol which could result in a higher serum level.
Food Interactions
  • 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.

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]
External Links
Human Metabolome Database
HMDB0005018
KEGG Drug
D07450
KEGG Compound
C06825
PubChem Compound
2162
PubChem Substance
46507214
ChemSpider
2077
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
ATC Codes
C09DX03 — Olmesartan medoxomil, amlodipine and hydrochlorothiazideC09DB01 — Valsartan and amlodipineC09DB04 — Telmisartan and amlodipineC09DB05 — Irbesartan and amlodipineC09DX01 — Valsartan, amlodipine and hydrochlorothiazideC10BX11 — Atorvastatin, amlodipine and perindoprilC09DB06 — Losartan and amlodipineC08GA02 — Amlodipine and diureticsC09DB07 — Candesartan and amlodipineC10BX03 — Atorvastatin and amlodipineC09DB02 — Olmesartan medoxomil and amlodipineC09BB07 — Ramipril and amlodipineC08CA01 — AmlodipineC09BB03 — Lisinopril and amlodipineC09BB04 — Perindopril and amlodipineC10BX09 — Rosuvastatin and amlodipineC09XA53 — Aliskiren and amlodipineC10BX07 — Rosuvastatin, amlodipine and lisinoprilC09BX01 — Perindopril, amlodipine and indapamideC09XA54 — Aliskiren, amlodipine and hydrochlorothiazide
AHFS Codes
  • 24:28.08 — Dihydropyridines
FDA label
Download (91.4 KB)
MSDS
Download (74.5 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
1CompletedNot AvailableHealhty1
1CompletedNot AvailableHealthy Volunteers14
1CompletedNot AvailableHealthy Volunteers / Pulmonary Disease, Chronic Obstructive1
1CompletedNot AvailableHigh Blood Pressure (Hypertension)3
1CompletedNot AvailableHypertension,Essential1
1CompletedBasic ScienceHigh Blood Pressure (Hypertension)1
1CompletedBasic ScienceHypertension(HTN)1
1CompletedDiagnosticHigh Blood Pressure (Hypertension)1
1CompletedOtherHigh Blood Pressure (Hypertension)1
1CompletedPreventionHealthy Volunteers / Pulmonary Disease, Chronic Obstructive1
1CompletedSupportive CareHealthy Male Volunteers1
1CompletedTreatmentBioequivalence1
1CompletedTreatmentCardiovascular Disease (CVD) / High Blood Pressure (Hypertension) / Human Immunodeficiency Virus (HIV) Infections1
1CompletedTreatmentErectile Dysfunction (ED)1
1CompletedTreatmentFasting2
1CompletedTreatmentFed1
1CompletedTreatmentHealthy Male Volunteers1
1CompletedTreatmentHealthy Volunteers19
1CompletedTreatmentHigh Blood Pressure (Hypertension)9
1CompletedTreatmentHigh Blood Pressure (Hypertension) / Hyperlipidemias3
1CompletedTreatmentHuman Immunodeficiency Virus (HIV)1
1CompletedTreatmentHypertension With Hyperlipidemia / Hypertention With Hyperlipidemia1
1CompletedTreatmentHypertension and Dyslipidemia1
1CompletedTreatmentType 2 Diabetes Mellitus1
1Not Yet RecruitingBasic ScienceHealthy Volunteers1
1Not Yet RecruitingTreatmentHealthy Volunteers1
1Not Yet RecruitingTreatmentHigh Blood Pressure (Hypertension)1
1RecruitingTreatmentHigh Blood Pressure (Hypertension)1
1RecruitingTreatmentHigh Blood Pressure (Hypertension) / Hyperlipidemias1
1TerminatedTreatmentHigh Blood Pressure (Hypertension) / Hyperlipidemias1
1Unknown StatusBasic ScienceHealthy Volunteers1
1WithdrawnTreatmentHepatitis C Viral Infection / High Blood Pressure (Hypertension)1
1, 2CompletedTreatmentPancreatitis1
1, 2RecruitingTreatmentMetastatic Triple Negative Breast Cancer1
2CompletedNot AvailableConcurrent Obesity / High Blood Pressure (Hypertension)1
2CompletedPreventionHigh Blood Pressure (Hypertension) / Hyperlipidemias1
2CompletedTreatmentAbdominal Aortic Aneurysms (AAA)1
2CompletedTreatmentAngina, Prinzmetal's1
2CompletedTreatmentCardiovascular Disease (CVD) / Heart Diseases / High Blood Pressure (Hypertension) / Vascular Diseases1
2CompletedTreatmentEndothelial Dysfunction / High Blood Pressure (Hypertension) / Insulin Resistance / Metabolic Syndromes1
2CompletedTreatmentHigh Blood Pressure (Hypertension)6
2CompletedTreatmentHypertension,Essential3
2RecruitingTreatmentHigh Blood Pressure (Hypertension)1
2RecruitingTreatmentHypertension,Essential1
2SuspendedTreatmentChronic Heart Failure (CHF)1
2TerminatedTreatmentAnkle Edema / High Blood Pressure (Hypertension)1
2TerminatedTreatmentHigh Blood Pressure (Hypertension) / Obesity, Abdominal1
2Unknown StatusTreatmentHypertension,Essential1
2, 3CompletedPreventionThalassaemic disorders1
2, 3CompletedTreatmentCardiac Failure / Congestive Heart Failure (CHF) / Heart Failure, Unspecified1
2, 3CompletedTreatmentGrade I or II Essential Hypertension1
2, 3CompletedTreatmentHypertension,Essential1
2, 3CompletedTreatmentThalassemia Major (TM)1
2, 3RecruitingPreventionCognitively Normal Older Adults / Family History of Alzheimer's Disease / High Blood Pressure (Hypertension) / Subjective Cognitive Decline1
2, 3RecruitingTreatmentHigh Blood Pressure (Hypertension) / Sleep Apnea Syndrome1
2, 3Unknown StatusTreatmentHypertension,Essential2
3CompletedDiagnosticHigh Blood Pressure (Hypertension)1
3CompletedPreventionAtherosclerosis / Cardiovascular Disease (CVD) / Coronary Heart Disease (CHD) / Diabetes Mellitus (DM) / High Blood Cholesterol Level / High Blood Pressure (Hypertension) / Type 2 Diabetes Mellitus1
3CompletedPreventionCardiovascular Disease (CVD) / Coronary Heart Disease (CHD) / Diabetes Mellitus (DM) / Heart Diseases / Heart Failure, Unspecified / High Blood Cholesterol Level / High Blood Pressure (Hypertension) / Myocardial Infarction / Myocardial Ischemia1
3CompletedTreatmentChronic Kidney Disease (CKD) / High Blood Pressure (Hypertension)1
3CompletedTreatmentDyslipidemia With Hypertension1
3CompletedTreatmentDyslipidemias / High Blood Pressure (Hypertension)2
3CompletedTreatmentHigh Blood Pressure (Hypertension)59
3CompletedTreatmentHigh Blood Pressure (Hypertension) / Metabolic Syndromes1
3CompletedTreatmentHigh Blood Pressure (Hypertension) / Obstructive Sleep Apnea (OSA)1
3CompletedTreatmentHigh Blood Pressure (Hypertension) / Sleep Apnea Syndrome1
3CompletedTreatmentHigh Blood Pressure (Hypertension) / Transplantation, Kidney1
3CompletedTreatmentHypertension With Hyperlipidemia1
3CompletedTreatmentHypertension,Essential12
3CompletedTreatmentHypertension; Hypertrophy, Left Ventricular1
3CompletedTreatmentModerate to Severe Hypertension1
3CompletedTreatmentProteinuria1
3CompletedTreatmentAcute iron intoxication / Thalassaemic disorders1
3RecruitingTreatmentCerebral Small Vessels Disease1
3RecruitingTreatmentDyslipidemias / Hypertension,Essential1
3RecruitingTreatmentHigh Blood Pressure (Hypertension)1
3RecruitingTreatmentHigh Blood Pressure (Hypertension) / Hyperlipidemias2
3TerminatedTreatmentCardiovascular Events1
3Unknown StatusTreatmentDepression1
3Unknown StatusTreatmentDiabetes Mellitus (DM) / Hypertension,Essential1
3Unknown StatusTreatmentHypertension,Essential1
3WithdrawnTreatmentHigh Blood Pressure (Hypertension)2
4Active Not RecruitingBasic ScienceArterial hypoxia / Obstructive Sleep Apnea (OSA) / Sleep Apnea Syndrome1
4Active Not RecruitingTreatmentChronic Hypertension in Pregnancy1
4CompletedNot AvailableHigh Blood Pressure (Hypertension)1
4CompletedHealth Services ResearchAsthma Bronchial1
4CompletedOtherCoronary Artery Disease / Type 2 Diabetes Mellitus1
4CompletedPreventionCardiovascular Disease (CVD) / High Blood Pressure (Hypertension)1
4CompletedPreventionCoronary Artery Atherosclerosis / High Blood Pressure (Hypertension)1
4CompletedPreventionHigh Blood Pressure (Hypertension)2
4CompletedPreventionHigh Blood Pressure (Hypertension) / Type 2 Diabetes Mellitus1
4CompletedPreventionNonvalvular Atrial Fibrillation2
4CompletedPreventionWe Searched for the Effects of Calcium Channel Blocker Amlodipine on the Clinical and Laboratory Parameters of Diabetic Patients With Proteinuria1
4CompletedTreatmentAlbuminuria1
4CompletedTreatmentAlbuminuria / High Blood Pressure (Hypertension) / Type 2 Diabetes Mellitus1
4CompletedTreatmentAngina Pectoris / High Blood Cholesterol Level / High Blood Pressure (Hypertension)1
4CompletedTreatmentAnginal Pain1
4CompletedTreatmentBMI >30 kg/m2 / Diabetes Mellitus (DM) / High Blood Pressure (Hypertension)1
4CompletedTreatmentBMI >30 kg/m2 / High Blood Pressure (Hypertension)1
4CompletedTreatmentBlood Pressures1
4CompletedTreatmentCardiovascular Disease (CVD) / Chronic Kidney Disease (CKD) / Hypertension,Essential / Strokes1
4CompletedTreatmentChronic Obstructive Pulmonary Disease (COPD)1
4CompletedTreatmentChronic Renal Failure (CRF)1
4CompletedTreatmentDiabetes Mellitus (DM) / High Blood Pressure (Hypertension)1
4CompletedTreatmentDiabetes Mellitus (DM) / High Blood Pressure (Hypertension) / Proteinuria2
4CompletedTreatmentDiastolic Dysfunction / High Blood Pressure (Hypertension)1
4CompletedTreatmentDyslipidemias / High Blood Pressure (Hypertension)3
4CompletedTreatmentEssential Hypertension ( Mild to Moderate)1
4CompletedTreatmentHigh Blood Cholesterol Level / High Blood Pressure (Hypertension)1
4CompletedTreatmentHigh Blood Pressure (Hypertension)32
4CompletedTreatmentHigh Blood Pressure (Hypertension) / Hyperlipidemias1
4CompletedTreatmentHigh Blood Pressure (Hypertension) / Hypertension,Essential1
4CompletedTreatmentHigh Blood Pressure (Hypertension) / Left Ventricle Hypertrophy1
4CompletedTreatmentHigh Blood Pressure (Hypertension) / Left Ventricular Hypertrophy1
4CompletedTreatmentHigh Blood Pressure (Hypertension) / Metabolic Syndromes1
4CompletedTreatmentHigh Blood Pressure (Hypertension) / Pharmacogenetics1
4CompletedTreatmentHigh Blood Pressure (Hypertension) / Strokes1
4CompletedTreatmentHigh Blood Pressure (Hypertension) / Type 2 Diabetes Mellitus1
4CompletedTreatmentHypertension,Essential5
4CompletedTreatmentIschaemic Heart Diseases1
4CompletedTreatmentMyocardial Ischemia1
4CompletedTreatmentStage 2 Systolic Hypertension1
4CompletedTreatmentStroke, Ischemic1
4Not Yet RecruitingTreatmentASCVD / High Blood Pressure (Hypertension) / Impaired Fasting Glucose (IFG)1
4Not Yet RecruitingTreatmentArterial Hypertension2
4Not Yet RecruitingTreatmentBlood Pressures / Cardiovascular Risk Factors / Prehypertension / Strokes / Type 2 Diabetes Mellitus1
4Not Yet RecruitingTreatmentFeeling Anxious / High Blood Pressure (Hypertension)1
4Not Yet RecruitingTreatmentHigh Blood Pressure (Hypertension)1
4Not Yet RecruitingTreatmentBone destruction / Postmenopausal Osteoporosis (PMO)1
4Not Yet RecruitingTreatmentQuality of Life1
4RecruitingDiagnosticAsthma Bronchial / Chronic Obstructive Pulmonary Disease (COPD) / Overlap Syndrome1
4RecruitingDiagnosticHigh Blood Pressure (Hypertension) / Type 2 Diabetes Mellitus1
4RecruitingPreventionBlood Pressures / High Blood Pressure (Hypertension) / Strokes1
4RecruitingTreatmentAcute Exacerbation of Chronic Obstructive Pulmonary Disease / Chronic Obstructive Pulmonary Disease (COPD)1
4RecruitingTreatmentAortic Valve Insufficiency / Aortic Valve Stenosis / High Blood Pressure (Hypertension) / Left Ventricular Hypertrophy / LVM1
4RecruitingTreatmentArterial Hypertension / Blood Pressures / Dyslipidemias / Lipid Metabolism Disorders1
4RecruitingTreatmentArterial Hypertension / High Blood Pressure (Hypertension)1
4RecruitingTreatmentEfficacy of Olmesartan on Cerebral Glucose Metabolism in Essential Hypertension1
4RecruitingTreatmentHigh Blood Pressure (Hypertension)5
4RecruitingTreatmentNonalcoholic Fatty Liver Disease (NAFLD)1
4RecruitingTreatmentPediatric Hypertension1
4RecruitingTreatmentProteinuria / Renal Insufficiency,Chronic1
4RecruitingTreatmentPulmonary Disease, Chronic Obstructive1
4TerminatedNot AvailableHypertension and Cardiovascular Risk Factors1
4TerminatedPreventionAtherosclerosis / Carotid Artery Stenosis / Strokes1
4TerminatedTreatmentDiabetes Mellitus (DM) / High Blood Pressure (Hypertension) / Stage 2 Hypertension1
4TerminatedTreatmentHigh Blood Pressure (Hypertension)1
4TerminatedTreatmentHypertension With Metabolic Syndrome1
4Unknown StatusDiagnosticCoronary Artery Disease1
4Unknown StatusPreventionDiabetic Nephropathies1
4Unknown StatusTreatmentAlbuminuria / Diabetes Mellitus (DM) / High Blood Pressure (Hypertension)1
4Unknown StatusTreatmentArterial and Arteriolar Disorders1
4Unknown StatusTreatmentBlood Pressures1
4Unknown StatusTreatmentCoronary Artery Disease2
4Unknown StatusTreatmentDialysis therapy / High Blood Pressure (Hypertension)1
4Unknown StatusTreatmentHigh Blood Pressure (Hypertension)5
4Unknown StatusTreatmentHypertension,Essential1
4WithdrawnDiagnosticBMI >30 kg/m2 / High Blood Pressure (Hypertension)1
4WithdrawnTreatmentDiabetes Mellitus (DM) / High Blood Pressure (Hypertension)1
4WithdrawnTreatmentHigh Blood Pressure (Hypertension)2
Not AvailableActive Not RecruitingTreatmentBeta Thalassemia Major1
Not AvailableCompletedNot AvailableAngina Pectoris / Dyslipidemia (Fredrickson Type Ⅱa) / High Blood Cholesterol Level / High Blood Pressure (Hypertension)1
Not AvailableCompletedNot AvailableCardiovascular Disease (CVD) / Coronary Heart Disease (CHD) / Heart Diseases / High Blood Pressure (Hypertension) / Myocardial Infarction1
Not AvailableCompletedNot AvailableDiabetes Complications / Diabetes, Diabetes Mellitus Type 1 / Eye Diseases / Retinopathy, Diabetic1
Not AvailableCompletedNot AvailableHealthy Volunteers2
Not AvailableCompletedNot AvailableHigh Blood Pressure (Hypertension)5
Not AvailableCompletedDiagnosticArterial Hypertension1
Not AvailableCompletedDiagnosticHigh Blood Pressure (Hypertension)1
Not AvailableCompletedTreatmentBMI >30 kg/m2 / High Blood Pressure (Hypertension)1
Not AvailableCompletedTreatmentChronic Stable Angina Pectoris / High Blood Pressure (Hypertension) / Vasospastic Angina2
Not AvailableCompletedTreatmentDiabetes Mellitus (DM) / High Blood Pressure (Hypertension)1
Not AvailableCompletedTreatmentFemale Infertility Associated With Anovulation1
Not AvailableCompletedTreatmentHeart Failure With Preserved Ejection Fraction (HFpEF) / Left Ventricular Hypertrophy/Hypertension / Pulmonary Diseases1
Not AvailableCompletedTreatmentHigh Blood Pressure (Hypertension)2
Not AvailableCompletedTreatmentHigh Blood Pressure (Hypertension) / Lower Urinary Tract Symptoms (LUTS)1
Not AvailableCompletedTreatmentHigh Blood Pressure (Hypertension) / Plasma Renin Activity1
Not AvailableCompletedTreatmentHypertension,Essential1
Not AvailableCompletedTreatmentMyocardial Ischemia1
Not AvailableNot Yet RecruitingTreatmentHigh Blood Pressure (Hypertension)1
Not AvailableRecruitingNot AvailableChronic Obstructive Pulmonary Disease (COPD)1
Not AvailableRecruitingNot AvailableHypertension,Essential1
Not AvailableRecruitingNot AvailableLower Leg Edema / Orthostatic Hypertension1
Not AvailableRecruitingNot AvailableMetabolic Syndromes1
Not AvailableRecruitingNot AvailableObesity, Morbid1
Not AvailableRecruitingDiagnosticHigh Blood Pressure (Hypertension)1
Not AvailableRecruitingTreatmentAcute iron intoxication / Beta-Thalassemia1
Not AvailableRecruitingTreatmentChronic Obstructive Pulmonary Disease (COPD)1
Not AvailableTerminatedTreatmentAbdominal Aortic Aneurysms (AAA) / High Blood Pressure (Hypertension)1
Not AvailableTerminatedTreatmentAortic Compliance / Diastolic Function / Insulin Sensitivity1
Not AvailableTerminatedTreatmentHigh Blood Pressure (Hypertension)1
Not AvailableUnknown StatusNot AvailableArterial Hypertension / Diabetes Mellitus (DM)1
Not AvailableUnknown StatusTreatmentBlood Pressure Variability / Intracranial Artery Stenosis1
Not AvailableUnknown StatusTreatmentChronic Obstructive Pulmonary Disease (COPD)1
Not AvailableUnknown StatusTreatmentHigh 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
TabletOral10 mg/1
TabletOral2.5 mg/1
TabletOral5 mg/1
CapsuleOral
TabletOral10.00 mg
TabletOral5.00 mg
TabletOral
Kit
Tablet, film coatedOral
TabletOral10.0 mg
TabletOral5.0 mg
TabletOral10 mg
TabletOral5 mg
TabletOral2.5 mg
Tablet, multilayerOral
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)
CA2170278No1999-08-032014-08-10Canada
US6162802No1997-12-192017-12-19Us
US5969156Yes1997-01-082017-01-08Us
US6294197Yes1997-12-182017-12-18Us
US5559111Yes1999-01-212019-01-21Us
US6395728No1999-07-082019-07-08Us
US6828339No2002-11-202022-11-20Us
US5616599Yes1996-10-252016-10-25Us
US6455574No1998-08-112018-08-11Us
US8101599No2003-05-162023-05-16Us
US8475839Yes2003-11-162023-11-16Us
US8613949No2009-12-212029-12-21Us
US8618174No2001-11-152021-11-15Us
US8183295No2003-05-162023-05-16Us
US7846961No2009-10-052029-10-05Us
US6696481No2003-04-152023-04-15Us

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)178-179 °CNot Available
water solubility75.3 mg/LNot Available
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

Taxonomy

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
Dihydropyridinecarboxylic acid derivative / Chlorobenzene / Halobenzene / Aryl chloride / Aryl halide / Monocyclic benzene moiety / Dicarboxylic acid or derivatives / Benzenoid / Vinylogous amide / Alpha,beta-unsaturated carboxylic ester
show 25 more
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
ethyl ester, primary amino compound, methyl ester, monochlorobenzenes, dihydropyridine (CHEBI:2668)

Targets

Kind
Protein
Organism
Human
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. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
  2. Striessnig, J. (2004). Ca 2+ channel blockers. In Encyclopedic reference of molecular pharmacology (pp. 201-207). Berlin: Springer. [ISBN:9783540298328]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Inhibitor
General Function
Voltage-gated calcium 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. Plays an important role in excitation-...
Gene Name
CACNA2D1
Uniprot ID
P54289
Uniprot Name
Voltage-dependent calcium channel subunit alpha-2/delta-1
Molecular Weight
124566.93 Da
References
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
  2. Striessnig, J. (2004). Ca 2+ channel blockers. In Encyclopedic reference of molecular pharmacology (pp. 201-207). Berlin: Springer. [ISBN:9783540298328]
Kind
Protein
Organism
Human
Pharmacological action
Yes
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
CACNB2
Uniprot ID
Q08289
Uniprot Name
Voltage-dependent L-type calcium channel subunit beta-2
Molecular Weight
73579.925 Da
References
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
  2. Striessnig, J. (2004). Ca 2+ channel blockers. In Encyclopedic reference of molecular pharmacology (pp. 201-207). Berlin: Springer. [ISBN:9783540298328]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Inhibitor
General Function
Voltage-gated calcium channel activity involved sa node cell action potential
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
CACNA1D
Uniprot ID
Q01668
Uniprot Name
Voltage-dependent L-type calcium channel subunit alpha-1D
Molecular Weight
245138.75 Da
References
  1. Sinnegger-Brauns MJ, Huber IG, Koschak A, Wild C, Obermair GJ, Einzinger U, Hoda JC, Sartori SB, Striessnig J: Expression and 1,4-dihydropyridine-binding properties of brain L-type calcium channel isoforms. Mol Pharmacol. 2009 Feb;75(2):407-14. doi: 10.1124/mol.108.049981. Epub 2008 Nov 24. [PubMed:19029287]
Kind
Protein
Organism
Human
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
CACNA1S
Uniprot ID
Q13698
Uniprot Name
Voltage-dependent L-type calcium channel subunit alpha-1S
Molecular Weight
212348.1 Da
References
  1. Peterson BZ, Catterall WA: Allosteric interactions required for high-affinity binding of dihydropyridine antagonists to Ca(V)1.1 Channels are modulated by calcium in the pore. Mol Pharmacol. 2006 Aug;70(2):667-75. Epub 2006 May 4. [PubMed:16675661]
Kind
Protein
Organism
Human
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
Human
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
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
High voltage-gated calcium channel activity
Specific Function
Not Available
Gene Name
CACNB1
Uniprot ID
Q6TME4
Uniprot Name
Voltage-dependent L-type calcium channel subunit beta-1
Molecular Weight
23836.425 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
Human
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
Human
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]

Enzymes

Kind
Protein
Organism
Human
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. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
  3. Drug Interactions: Cytochrome P450 Drug Interaction Table [Link]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
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. Drug Interactions: Cytochrome P450 Drug Interaction Table [Link]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
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
CYP3A7
Uniprot ID
P24462
Uniprot Name
Cytochrome P450 3A7
Molecular Weight
57525.03 Da
References
  1. Drug Interactions: Cytochrome P450 Drug Interaction Table [Link]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen
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
CYP1A2
Uniprot ID
P05177
Uniprot Name
Cytochrome P450 1A2
Molecular Weight
58293.76 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. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
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]
  2. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
Kind
Protein
Organism
Human
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
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. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
Exhibits a high coumarin 7-hydroxylase activity. Can act in the hydroxylation of the anti-cancer drugs cyclophosphamide and ifosphamide. Competent in the metabolic activation of aflatoxin B1. Const...
Gene Name
CYP2A6
Uniprot ID
P11509
Uniprot Name
Cytochrome P450 2A6
Molecular Weight
56501.005 Da
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
Kind
Protein
Organism
Human
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. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
  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
Human
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
CYP2C9
Uniprot ID
P11712
Uniprot Name
Cytochrome P450 2C9
Molecular Weight
55627.365 Da
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
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. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256]

Transporters

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
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]

Drug created on June 13, 2005 07:24 / Updated on September 18, 2018 23:02