Identification

Name
Enalapril
Accession Number
DB00584  (APRD00510)
Type
Small Molecule
Groups
Approved, Vet approved
Description

Enalapril is a prodrug that belongs to the angiotensin-converting enzyme (ACE) inhibitor class of medications. It is rapidly metabolized in the liver to enalaprilat following oral administration. Enalaprilat is a potent, competitive inhibitor of ACE, the enzyme responsible for the conversion of angiotensin I (ATI) to angiotensin II (ATII). ATII regulates blood pressure and is a key component of the renin-angiotensin-aldosterone system (RAAS). Enalapril may be used to treat essential or renovascular hypertension and symptomatic congestive heart failure.

Structure
Thumb
Synonyms
  • (S)-1-(N-(1-(Ethoxycarbonyl)-3-phenylpropyl)-L-alanyl)-L-proline
  • (S)-1-{(S)-2-[1-((S)-ethoxycarbonyl)-3-phenyl-propylamino]-propionyl}-pyrrolidine-2-carboxylic acid
  • 1-(N-((S)-1-Carboxy-3-phenylpropyl)-L-alanyl)-L-proline 1'-ethyl ester
  • Analapril
  • Enalapril
  • Enalaprila
  • Enalaprilum
External IDs
C09AA02 / L 154739-01 D / MK 421
Product Ingredients
IngredientUNIICASInChI Key
Enalapril maleate9O25354EPJ76095-16-4OYFJQPXVCSSHAI-QFPUQLAESA-N
Enalapril sodium94A7UFL2SI149404-21-7FTTHROYWFRGKST-BDURURIASA-M
Active Moieties
NameKindUNIICASInChI Key
EnalaprilatprodrugQ508Q118JM76420-72-9LZFZMUMEGBBDTC-QEJZJMRPSA-N
Product Images
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Act EnalaprilTablet4 mgOralTeva2007-10-17Not applicableCanada
Act EnalaprilTablet16 mgOralTeva2007-10-17Not applicableCanada
Act EnalaprilTablet8 mgOralTeva2007-10-17Not applicableCanada
Act EnalaprilTablet2 mgOralTeva2007-10-17Not applicableCanada
EnalaprilTablet8 mgOralSivem Pharmaceuticals Ulc2015-08-10Not applicableCanada
EnalaprilTablet2 mgOralSivem Pharmaceuticals Ulc2015-08-10Not applicableCanada
EnalaprilTablet4.0 mgOralCobalt LaboratoriesNot applicableNot applicableCanada
EnalaprilTablet4 mgOralSanis Health Inc2013-02-13Not applicableCanada
EnalaprilTablet8 mgOralFrosst A Division Of Merck Canada IncNot applicableNot applicableCanada
EnalaprilTablet16 mgOralCobalt LaboratoriesNot applicableNot applicableCanada
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Apo-enalapril Tab 10mgTablet10 mgOralApotex Corporation1993-12-31Not applicableCanada
Apo-enalapril Tab 2.5mgTablet2.5 mgOralApotex Corporation1993-12-31Not applicableCanada
Apo-enalapril Tab 20mgTablet20 mgOralApotex Corporation1993-12-31Not applicableCanada
Apo-enalapril Tab 5mgTablet5 mgOralApotex Corporation1993-12-31Not applicableCanada
Ava-enalaprilTablet10.0 mgOralAvanstra Inc2011-10-112014-08-21Canada
Ava-enalaprilTablet5.0 mgOralAvanstra Inc2011-10-112014-08-21Canada
Ava-enalaprilTablet20.0 mgOralAvanstra Inc2011-10-112014-08-21Canada
Ava-enalaprilTablet2.5 mgOralAvanstra Inc2011-10-112014-08-21Canada
Dom-enalaprilTablet16 mgOralDominion PharmacalNot applicableNot applicableCanada
Dom-enalaprilTablet2.0 mgOralDominion PharmacalNot applicableNot applicableCanada
Mixture Products
NameIngredientsDosageRouteLabellerMarketing StartMarketing End
Enalapril Maleate and HydrochlorothiazideEnalapril maleate (5 mg/1) + Hydrochlorothiazide (12.5 mg/1)TabletOralApotex Corporation2007-06-192011-01-31Us60505 020820180907 15195 1ctfzx6
Enalapril Maleate and HydrochlorothiazideEnalapril maleate (10 mg/1) + Hydrochlorothiazide (25 mg/1)TabletOralMed Health Pharma2011-04-282012-06-13Us
Enalapril Maleate and HydrochlorothiazideEnalapril maleate (10 mg/1) + Hydrochlorothiazide (25 mg/1)TabletOralOceanside Pharmaceuticals1986-10-312018-08-31Us
Enalapril maleate and hydrochlorothiazideEnalapril maleate (5 mg/1) + Hydrochlorothiazide (12.5 mg/1)TabletOralMed Pharma Co., Ltd.2011-04-132012-04-25Us
Enalapril Maleate and HydrochlorothiazideEnalapril maleate (5 mg/1) + Hydrochlorothiazide (12.5 mg/1)TabletOralMylan Pharmaceuticals Inc.2001-09-19Not applicableUs00378 0712 01 nlmimage10 af4057d2
Enalapril maleate and hydrochlorothiazideEnalapril maleate (10 mg/1) + Hydrochlorothiazide (25 mg/1)TabletOralDr Reddy's Laboratories2001-10-15Not applicableUs
Enalapril Maleate and HydrochlorothiazideEnalapril maleate (5 mg/1) + Hydrochlorothiazide (12.5 mg/1)TabletOralEon Labs, Inc.2001-09-192012-02-29Us
Enalapril Maleate and HydrochlorothiazideEnalapril maleate (10 mg/1) + Hydrochlorothiazide (25 mg/1)TabletOralLake Erie Medical Dba Quality Care Produts Llc2009-07-23Not applicableUs
Enalapril Maleate and HydrochlorothiazideEnalapril maleate (10 mg/1) + Hydrochlorothiazide (25 mg/1)TabletOralAv Kare, Inc.2013-07-222016-04-06Us00093 1052 01 nlmimage10 ae29d76e
Enalapril Maleate and HydrochlorothiazideEnalapril maleate (10 mg/1) + Hydrochlorothiazide (25 mg/1)TabletOralPhysicians Total Care, Inc.2009-07-23Not applicableUs54868 510020180826 1962 1mwphfw
International/Other Brands
Acetec (Alphapharm) / Acetensil (Grünenthal) / Alapren (Ranbaxy) / Amotac (Mass Pharma) / Amprace (Merck Sharp & Dohme) / Dilvas (Cipla) / Diotensil (Mintlab) / Drepatil (Fada) / Enace (Abbott) / EnaHexal (Sandoz) / Enal (East West) / Enalapoten (Del Bel) / Enpril (Wockhardt) / Feliberal (Silanes) / Gadopril (Gador (Argentina)) / Glioten (Bago) / Kinfil (Nova Argentia (Argentina)) / Vasotec IV (Sandoz (Canada))
Categories
UNII
69PN84IO1A
CAS number
75847-73-3
Weight
Average: 376.4467
Monoisotopic: 376.199822016
Chemical Formula
C20H28N2O5
InChI Key
GBXSMTUPTTWBMN-XIRDDKMYSA-N
InChI
InChI=1S/C20H28N2O5/c1-3-27-20(26)16(12-11-15-8-5-4-6-9-15)21-14(2)18(23)22-13-7-10-17(22)19(24)25/h4-6,8-9,14,16-17,21H,3,7,10-13H2,1-2H3,(H,24,25)/t14-,16-,17-/m0/s1
IUPAC Name
(2S)-1-[(2S)-2-{[(2S)-1-ethoxy-1-oxo-4-phenylbutan-2-yl]amino}propanoyl]pyrrolidine-2-carboxylic acid
SMILES
CCOC(=O)[C@H](CCC1=CC=CC=C1)N[C@@H](C)C(=O)N1CCC[C@H]1C(O)=O

Pharmacology

Indication

For the treatment of essential or renovascular hypertension and symptomatic congestive heart failure. It may be used alone or in combination with thiazide diuretics.

Associated Conditions
Pharmacodynamics

Enalapril is a prodrug that is rapidly metabolized by liver esterases to enalaprilat following oral administration. Enalapril itself has little pharmacologic activity. Enalaprilat lowers blood pressure by antagonizing the effect of the RAAS. The RAAS is a homeostatic mechanism for regulating hemodynamics, water and electrolyte balance. During sympathetic stimulation or when renal blood pressure or blood flow is reduced, renin is released from the granular cells of the juxtaglomerular apparatus in the kidneys. In the blood stream, renin cleaves circulating angiotensinogen to ATI, which is subsequently cleaved to ATII by ACE. ATII increases blood pressure using a number of mechanisms. First, it stimulates the secretion of aldosterone from the adrenal cortex. Aldosterone travels to the distal convoluted tubule (DCT) and collecting tubule of nephrons where it increases sodium and water reabsorption by increasing the number of sodium channels and sodium-potassium ATPases on cell membranes. Second, ATII stimulates the secretion of vasopressin (also known as antidiuretic hormone or ADH) from the posterior pituitary gland. ADH stimulates further water reabsorption from the kidneys via insertion of aquaporin-2 channels on the apical surface of cells of the DCT and collecting tubules. Third, ATII increases blood pressure through direct arterial vasoconstriction. Stimulation of the Type 1 ATII receptor on vascular smooth muscle cells leads to a cascade of events resulting in myocyte contraction and vasoconstriction. In addition to these major effects, ATII induces the thirst response via stimulation of hypothalamic neurons. ACE inhibitors inhibit the rapid conversion of ATI to ATII and antagonize RAAS-induced increases in blood pressure. ACE (also known as kininase II) is also involved in the enzymatic deactivation of bradykinin, a vasodilator. Inhibiting the deactivation of bradykinin increases bradykinin levels and may sustain the effects of enalaprilat by causing increased vasodilation and decreased blood pressure.

Mechanism of action

There are two isoforms of ACE: the somatic isoform, which exists as a glycoprotein comprised of a single polypeptide chain of 1277; and the testicular isoform, which has a lower molecular mass and is thought to play a role in sperm maturation and binding of sperm to the oviduct epithelium. Somatic ACE has two functionally active domains, N and C, which arise from tandem gene duplication. Although the two domains have high sequence similarity, they play distinct physiological roles. The C-domain is predominantly involved in blood pressure regulation while the N-domain plays a role in hematopoietic stem cell differentiation and proliferation. ACE inhibitors bind to and inhibit the activity of both domains, but have much greater affinity for and inhibitory activity against the C-domain. Enalaprilat, the principle active metabolite of enalapril, competes with ATI for binding to ACE and inhibits and enzymatic proteolysis of ATI to ATII. Decreasing ATII levels in the body decreases blood pressure by inhibiting the pressor effects of ATII as described in the Pharmacology section above. Enalapril also causes an increase in plasma renin activity likely due to a loss of feedback inhibition mediated by ATII on the release of renin and/or stimulation of reflex mechanisms via baroreceptors. Enalaprilat's affinity for ACE is approximately 200,000 times greater than that of ATI and 300-1000 times greater than that enalapril.

TargetActionsOrganism
AAngiotensin-converting enzyme
inhibitor
Human
Absorption

55-75%, absorption is unaffected by food; enalaprilat (clinically administered IV) is poorly absorbed, 3-12%, due to its high polarity.

Volume of distribution
Not Available
Protein binding

50-60% of enalaprilat is bound to plasma proteins

Metabolism

~ 60% of absorbed dose is extensively hydrolyzed to enalaprilat, primarily by liver esterases

Route of elimination

Excretion of enalapril is primarily renal.

Half life

< 2 hours for unchanged enalapril in health individuals, may be increased in those with congestive heart failure (3.4 and 5.8 hours for single 5- and 10-mg doses, respectively). The average terminal half life of enalaprilat is 35-38 hours. The effective half life following multiple doses is 11-14 hours.

Clearance
Not Available
Toxicity

Overdosage may result in marked hypotension and stupor. Most common adverse effects include hypotension, headache, dizziness and fatigue.

Affected organisms
  • Humans and other mammals
Pathways
PathwayCategory
Enalapril Action PathwayDrug action
Enalapril Metabolism PathwayDrug metabolism
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
(R)-warfarinThe metabolism of (R)-warfarin can be decreased when combined with Enalapril.
(S)-WarfarinThe metabolism of (S)-Warfarin can be decreased when combined with Enalapril.
3,5-diiodothyropropionic acidThe metabolism of 3,5-diiodothyropropionic acid can be decreased when combined with Enalapril.
4-hydroxycoumarinThe metabolism of 4-hydroxycoumarin can be decreased when combined with Enalapril.
5-androstenedioneThe metabolism of 5-androstenedione can be decreased when combined with Enalapril.
6-Deoxyerythronolide BThe metabolism of Enalapril can be decreased when combined with 6-Deoxyerythronolide B.
6-O-benzylguanineThe metabolism of 6-O-benzylguanine can be decreased when combined with Enalapril.
AbemaciclibThe metabolism of Abemaciclib can be decreased when combined with Enalapril.
AbirateroneThe metabolism of Abiraterone can be decreased when combined with Enalapril.
AcalabrutinibThe metabolism of Enalapril can be decreased when combined with Acalabrutinib.
Food Interactions
  • Enalapril decreases the excretion of potassium. Salt substitutes containing potassium increase the risk of hyperkalemia.
  • Herbs that may attenuate the antihypertensive effect of enalapril include: bayberry, blue cohash, cayenne, ephedra, ginger, ginseng (American), kola and licorice.
  • High salt intake may attenuate the antihypertensive effect of enalapril.
  • Take without regard to meals.

References

Synthesis Reference

K. S. Keshava Murthy, Andrew Burchat, Gamini Weeratunga, "Sodium enalapril complex and the use thereof to make sodium enalapril." U.S. Patent US5637730, issued February, 1983.

US5637730
General References
  1. Florey, Klaus;Al-Badr, Abdullah A.;Brenner, Gerald S. (1987). Analytical Profiles of Drug Substances (16th ed.). Elsevier Science & Technology Books. [ISBN:978-0-12-260816-2]
External Links
Human Metabolome Database
HMDB0014722
KEGG Compound
C06977
PubChem Compound
5388962
PubChem Substance
46507920
ChemSpider
4534998
BindingDB
50017129
ChEBI
4784
ChEMBL
CHEMBL578
Therapeutic Targets Database
DAP001374
PharmGKB
PA449456
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
PDRhealth
PDRhealth Drug Page
Wikipedia
Enalapril
ATC Codes
C09BB06 — Enalapril and nitrendipineC09BB02 — Enalapril and lercanidipineC09AA02 — EnalaprilC09BA02 — Enalapril and diuretics
AHFS Codes
  • 24:32.04 — Angiotensin-converting Enzyme Inhibitors
  • 24:32.20 — Mineralocorticoid (Aldosterone) Receptor Antagonists
FDA label
Download (939 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
0CompletedBasic ScienceEsophagus, Barrett1
1CompletedNot AvailableHealthy Volunteers / Pharmacokinetics of Enalapril1
1CompletedTreatmentErectile Dysfunction (ED)1
1CompletedTreatmentHigh Blood Pressure (Hypertension)1
1RecruitingTreatmentHypertension, Resistant to Conventional Therapy1
1Unknown StatusNot AvailableDiabetic Macular Ischemia1
1Unknown StatusTreatmentHeart Failure, Unspecified1
1, 2Unknown StatusTreatmentRenal Insufficiency,Chronic1
2CompletedNot AvailableDiabetes, Diabetes Mellitus Type 11
2CompletedPreventionLung Cancers / Radiation Pneumonitis1
2CompletedPreventionRheumatoid Arthritis1
2CompletedTreatmentCardiovascular Disease (CVD) / Heart Diseases / High Blood Pressure (Hypertension) / Vascular Diseases1
2CompletedTreatmentHigh Blood Pressure (Hypertension)1
2CompletedTreatmentHypertension,Essential1
2CompletedTreatmentIntracerebral Hemorrhage1
2CompletedTreatmentPseudohypoaldosteronism1
2Not Yet RecruitingTreatmentCardiovascular Disease (CVD) / Pre-Eclampsia Onset Less Than 37 Weeks (Diagnosis)1
2RecruitingTreatmentIntracerebral Hemorrhage1
2TerminatedTreatmentMetastatic Malignant Melanoma / Unresectable Malignant Melanoma1
2, 3CompletedPreventionHypertension Secondary to Kidney Transplant1
2, 3RecruitingTreatmentAngioplasty, Balloon, Coronary / Contrast Media / Coronary Heart Disease (CHD) / High Blood Pressure (Hypertension) / Homocysteine / Renal Dysfunction1
2, 3RecruitingTreatmentPediatric Heart Failure1
3Active Not RecruitingTreatmentHeart Failure With Reduced Ejection Fraction (HFrEF)1
3Active Not RecruitingTreatmentMalignancies1
3CompletedPreventionAutologous Hematopoietic Stem Cell Transplantation / Leukemia Acute Myeloid Leukemia (AML) / Lymphoid Neoplasms / Malignant Lymphomas / Multiple Myeloma (MM) / Precursor-cell Lymphoblastic Leukemia-Lymphoma1
3CompletedPreventionCardiovascular Disease (CVD) / Coronary Heart Disease (CHD) / Heart Diseases / Heart Failure, Unspecified / High Blood Pressure (Hypertension) / Myocardial Ischemia1
3CompletedPreventionHigh Blood Pressure (Hypertension) / Type 2 Diabetes Mellitus1
3CompletedSupportive CareCardiac Toxicity / Unspecified Childhood Solid Tumor, Protocol Specific1
3CompletedTreatmentCardiovascular Disease (CVD) / Heart Diseases / Heart Failure, Unspecified / Myocardial Diseases1
3CompletedTreatmentChronic Heart Failure (CHF)1
3CompletedTreatmentChronic Heart Failure With Reduced Ejection Fraction (HFrEF)1
3CompletedTreatmentCongestive Cardiomyopathy / High Blood Pressure (Hypertension)1
3CompletedTreatmentCongestive Heart Failure (CHF) / Heart Defects,Congenital1
3CompletedTreatmentCongestive Heart Failure (CHF) / Heart Failure With Preserved Ejection Fraction (HFpEF)1
3CompletedTreatmentHigh Blood Pressure (Hypertension)5
3CompletedTreatmentMuscular Dystrophy / Myocardial Fibrosis1
3CompletedTreatmentProteinuria1
3RecruitingPreventionCancer, Breast1
3RecruitingTreatmentHeart Failure With Preserved Ejection Fraction (HFpEF)1
3TerminatedTreatmentCongestive Heart Failure (CHF) / Heart Defects,Congenital / Heart Septal Defects, Ventricular1
3TerminatedTreatmentHeart Failure With Reduced Ejection Fraction (HFrEF)1
4CompletedBasic ScienceCarboxylesterase 1 (CES1) Genotype / CES1 Activity1
4CompletedBasic ScienceHigh Blood Pressure (Hypertension) / Metabolic Syndromes1
4CompletedOtherHeart Failure With Reduced Ejection Fraction (HFrEF)1
4CompletedPreventionCardiotoxicity / Chemotherapeutic Toxicity / Chemotherapy-Induced Cardiotoxicity Revealed by TnI Increase1
4CompletedPreventionHypertension,Essential1
4CompletedTreatmentCardiovascular Disease (CVD) / Chronic Kidney Disease (CKD) / Hypertension,Essential / Strokes1
4CompletedTreatmentHeart Failure, Unspecified / Ventricular Dysfunction, Left1
4CompletedTreatmentHigh Blood Pressure (Hypertension)3
4CompletedTreatmentHigh Blood Pressure (Hypertension) / Induction of intra-operative hypotension1
4CompletedTreatmentMacroalbuminuric Diabetic Nephropathy1
4Not Yet RecruitingOtherACL Injury1
4Not Yet RecruitingTreatmentHypertension,Essential1
4RecruitingPreventionCognitive Impairments / Delirium / Depression / Dexmedetomidine / Postoperative Cognitive Dysfunction1
4RecruitingScreeningHealthy Volunteers1
4RecruitingSupportive CareAcute Heart Failure (AHF)1
4RecruitingTreatmentBody Composition / Exercise Tolerance / Heart Failure, Unspecified / Strength, Muscle / Vasodilation1
4RecruitingTreatmentChronic Heart Failure With Reduced Ejection Fraction (HFrEF)1
4RecruitingTreatmentHeart Failure With Reduced Ejection Fraction (HFrEF)1
4RecruitingTreatmentHigh Blood Pressure (Hypertension)1
4RecruitingTreatmentRecurrent IgA Nephropathy1
4TerminatedPreventionDiabetes Mellitus (DM) / High Blood Pressure (Hypertension)1
4Unknown StatusPreventionAtherosclerosis / Cardiovascular Disease (CVD)1
4Unknown StatusPreventionContinuous ambulatory peritoneal dialysis therapy1
4Unknown StatusTreatmentCardiovascular Disease (CVD) / Chronic Renal Failure (CRF)1
4Unknown StatusTreatmentHeart Failure, Unspecified1
4WithdrawnPreventionHigh Blood Pressure (Hypertension) / Hyperhomocysteinaemia1
4WithdrawnTreatmentHeart Failure With Reduced Ejection Fraction (HFrEF)1
Not AvailableCompletedNot AvailableFabry's Disease / Proteinuria1
Not AvailableCompletedSupportive CareOrthognathic Surgery1
Not AvailableCompletedTreatmentDiabetic Nephropathies / Microalbuminuria1
Not AvailableCompletedTreatmentDiabetic Nephropathies / Proteinuria1
Not AvailableCompletedTreatmentHigh Blood Pressure (Hypertension) / Type 2 Diabetes Mellitus1
Not AvailableCompletedTreatmentIgA Glomerulonephritis1
Not AvailableCompletedTreatmentRenal Transplant Patients1
Not AvailableRecruitingNot AvailableObesity, Morbid1
Not AvailableRecruitingPreventionAtherosclerosis / Nephritis, Lupus1
Not AvailableTerminatedTreatmentSickle Cell Disorders1
Not AvailableUnknown StatusPreventionMicroalbuminuria / Sickle Cell Nephropathy1
Not AvailableUnknown StatusPreventionPre-Diabetic / Pre-Hypertension1
Not AvailableUnknown StatusTreatmentCancer, Breast1

Pharmacoeconomics

Manufacturers
  • Apotex inc
  • Apothecon inc div bristol myers squibb
  • Ivax pharmaceuticals inc sub teva pharmaceuticals usa
  • Krka dd novo mesto
  • Lek pharmaceuticals d d
  • Mylan pharmaceuticals inc
  • Ranbaxy laboratories ltd
  • Sandoz inc
  • Taro pharmaceutical industries ltd
  • Teva pharmaceuticals usa inc
  • Watson laboratories inc
  • Wockhardt americas inc
  • Biovail laboratories international srl
  • Bedford laboratories div ben venue laboratories inc
  • Hikma farmaceutica (portugal) sa
  • Hospira inc
  • Teva parenteral medicines inc
Packagers
  • Advanced Pharmaceutical Services Inc.
  • Amerisource Health Services Corp.
  • Apace Packaging
  • Apotex Inc.
  • Apotheca Inc.
  • A-S Medication Solutions LLC
  • Baxter International Inc.
  • Bedford Labs
  • Ben Venue Laboratories Inc.
  • Bryant Ranch Prepack
  • BTA Pharmaceuticals
  • California Clinical Pharmacy Inc.
  • Cardinal Health
  • Comprehensive Consultant Services Inc.
  • Corepharma LLC
  • Coupler Enterprises Inc.
  • Direct Dispensing Inc.
  • Dispensing Solutions
  • Diversified Healthcare Services Inc.
  • Emcure Pharmaceuticals Ltd.
  • Eon Labs
  • Heartland Repack Services LLC
  • Hikma Pharmaceuticals
  • Hospira Inc.
  • Ivax Pharmaceuticals
  • Krka d.d. Novo Mesto
  • Lake Erie Medical and Surgical Supply
  • Lek Pharmaceuticals Inc.
  • Major Pharmaceuticals
  • Medisca Inc.
  • Merck & Co.
  • Merrell Pharmaceuticals Inc.
  • Murfreesboro Pharmaceutical Nursing Supply
  • Mylan
  • Neuman Distributors Inc.
  • Nucare Pharmaceuticals Inc.
  • Ohm Laboratories Inc.
  • Palmetto Pharmaceuticals Inc.
  • Par Pharmaceuticals
  • Patheon Inc.
  • PCA LLC
  • PD-Rx Pharmaceuticals Inc.
  • Pharmaceutical Utilization Management Program VA Inc.
  • Pharmedix
  • Pharmpak Inc.
  • Physicians Total Care Inc.
  • Preferred Pharmaceuticals Inc.
  • Prepackage Specialists
  • Prepak Systems Inc.
  • Ranbaxy Laboratories
  • Rebel Distributors Corp.
  • Remedy Repack
  • Sandhills Packaging Inc.
  • Sandoz
  • Southwood Pharmaceuticals
  • Taro Pharmaceuticals USA
  • Teva Pharmaceutical Industries Ltd.
  • Tya Pharmaceuticals
  • UDL Laboratories
  • Vangard Labs Inc.
  • Watson Pharmaceuticals
  • West-Ward Pharmaceuticals
  • Wockhardt Ltd.
Dosage forms
FormRouteStrength
TabletOral10 mg
TabletOral2.5 mg
TabletOral20 mg
TabletOral5 mg
TabletOral10.0 mg
TabletOral20.0 mg
TabletOral5.0 mg
TabletOral10 mg/1
TabletOral2.5 mg/1
TabletOral20 mg/1
TabletOral5 mg/1
Tablet, solubleOral10 mg/1
Tablet, solubleOral2.5 mg/1
Tablet, solubleOral20 mg/1
Tablet, solubleOral5 mg/1
Kit1 mg/1mL
SolutionOral1 mg/1mL
Tablet, extended releaseOral
TabletOral32 mg
TabletOral2 mg
TabletOral4.0 mg
TabletOral8.0 mg
TabletOral16 mg
TabletOral2.0 mg
TabletOral4 mg
TabletOral8 mg
TabletOral
Prices
Unit descriptionCostUnit
Enalapril maleate powder9.18USD g
Enalaprilat 1.25 mg/ml vial3.6USD ml
Vasotec 20 mg tablet3.36USD tablet
Vaseretic 10-25 mg tablet3.15USD tablet
Vasotec 10 mg tablet2.63USD tablet
Vasotec 5 mg tablet2.08USD tablet
Vasotec 2.5 mg tablet1.65USD tablet
Enalapril maleate 20 mg tablet1.56USD tablet
Vaseretic 5-12.5 mg tablet1.49USD tablet
Vasotec 20 mg Tablet1.34USD tablet
Vasotec 10 mg Tablet1.11USD tablet
Enalapril maleate 10 mg tablet1.09USD tablet
Enalapril maleate 5 mg tablet1.03USD tablet
Vasotec 5 mg Tablet0.92USD tablet
Enalapril maleate 2.5 mg tablet0.82USD tablet
Vasotec 2.5 mg Tablet0.78USD tablet
Apo-Enalapril 20 mg Tablet0.75USD tablet
Co Enalapril 20 mg Tablet0.75USD tablet
Mylan-Enalapril 20 mg Tablet0.75USD tablet
Novo-Enalapril 20 mg Tablet0.75USD tablet
Pms-Enalapril 20 mg Tablet0.75USD tablet
Ratio-Enalapril 20 mg Tablet0.75USD tablet
Sandoz Enalapril 20 mg Tablet0.75USD tablet
Taro-Enalapril 20 mg Tablet0.75USD tablet
Apo-Enalapril 10 mg Tablet0.62USD tablet
Co Enalapril 10 mg Tablet0.62USD tablet
Mylan-Enalapril 10 mg Tablet0.62USD tablet
Novo-Enalapril 10 mg Tablet0.62USD tablet
Pms-Enalapril 10 mg Tablet0.62USD tablet
Ratio-Enalapril 10 mg Tablet0.62USD tablet
Sandoz Enalapril 10 mg Tablet0.62USD tablet
Taro-Enalapril 10 mg Tablet0.62USD tablet
Apo-Enalapril 5 mg Tablet0.52USD tablet
Co Enalapril 5 mg Tablet0.52USD tablet
Mylan-Enalapril 5 mg Tablet0.52USD tablet
Novo-Enalapril 5 mg Tablet0.52USD tablet
Pms-Enalapril 5 mg Tablet0.52USD tablet
Ratio-Enalapril 5 mg Tablet0.52USD tablet
Sandoz Enalapril 5 mg Tablet0.52USD tablet
Taro-Enalapril 5 mg Tablet0.52USD tablet
Apo-Enalapril 2.5 mg Tablet0.44USD tablet
Co Enalapril 2.5 mg Tablet0.44USD tablet
Mylan-Enalapril 2.5 mg Tablet0.44USD tablet
Novo-Enalapril 2.5 mg Tablet0.44USD tablet
Pms-Enalapril 2.5 mg Tablet0.44USD tablet
Ratio-Enalapril 2.5 mg Tablet0.44USD tablet
Sandoz Enalapril 2.5 mg Tablet0.44USD tablet
Taro-Enalapril 2.5 mg Tablet0.44USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US8778366No2014-07-152032-11-06Us
US8568747No2013-10-292032-11-06Us
US9669008No2017-06-062036-03-25Us
US9808442No2017-11-072036-03-25Us
US9855214No2018-01-022032-11-06Us
US9968553No2018-05-152032-11-06Us
US10039745No2016-03-252036-03-25Us

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)143-144.5 °CNot Available
water solubility1.64E+004 mg/L (at 25 °C)MCFARLAND,JW ET AL. (2001)
logP0.07HANSCH,C ET AL. (1995)
Caco2 permeability-5.64ADME Research, USCD
pKa2.97 (the carboxyl group) and 5.35 (the amine group) at 25°CNot Available
Predicted Properties
PropertyValueSource
Water Solubility0.213 mg/mLALOGPS
logP0.19ALOGPS
logP0.59ChemAxon
logS-3.2ALOGPS
pKa (Strongest Acidic)3.67ChemAxon
pKa (Strongest Basic)5.2ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area95.94 Å2ChemAxon
Rotatable Bond Count10ChemAxon
Refractivity99.57 m3·mol-1ChemAxon
Polarizability40.41 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.7428
Blood Brain Barrier-0.9659
Caco-2 permeable-0.8956
P-glycoprotein substrateSubstrate0.7691
P-glycoprotein inhibitor INon-inhibitor0.6681
P-glycoprotein inhibitor IINon-inhibitor0.5136
Renal organic cation transporterNon-inhibitor0.8442
CYP450 2C9 substrateNon-substrate0.8632
CYP450 2D6 substrateNon-substrate0.9116
CYP450 3A4 substrateNon-substrate0.5696
CYP450 1A2 substrateNon-inhibitor0.9125
CYP450 2C9 inhibitorNon-inhibitor0.9154
CYP450 2D6 inhibitorNon-inhibitor0.9231
CYP450 2C19 inhibitorNon-inhibitor0.9025
CYP450 3A4 inhibitorNon-inhibitor0.8309
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.6825
Ames testNon AMES toxic0.9383
CarcinogenicityNon-carcinogens0.9216
BiodegradationNot ready biodegradable0.8686
Rat acute toxicity1.8269 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9719
hERG inhibition (predictor II)Non-inhibitor0.7456
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-QFT , negativeLC-MS/MSsplash10-004i-0809000000-0e192d1573028e60641c
LC-MS/MS Spectrum - LC-ESI-QFT , positiveLC-MS/MSsplash10-003r-1859000000-8b202071e8860792a59f

Taxonomy

Description
This compound belongs to the class of organic compounds known as dipeptides. These are organic compounds containing a sequence of exactly two alpha-amino acids joined by a peptide bond.
Kingdom
Organic compounds
Super Class
Organic acids and derivatives
Class
Carboxylic acids and derivatives
Sub Class
Amino acids, peptides, and analogues
Direct Parent
Dipeptides
Alternative Parents
Proline and derivatives / Alpha amino acid esters / N-acyl-L-alpha-amino acids / Alpha amino acid amides / Pyrrolidine carboxylic acids / N-acylpyrrolidines / Aralkylamines / Fatty acid esters / Benzene and substituted derivatives / Dicarboxylic acids and derivatives
show 10 more
Substituents
Alpha-dipeptide / N-acyl-alpha amino acid or derivatives / N-acyl-alpha-amino acid / N-acyl-l-alpha-amino acid / Proline or derivatives / Alpha-amino acid ester / Alpha-amino acid amide / Alpha-amino acid or derivatives / Pyrrolidine carboxylic acid or derivatives / Pyrrolidine carboxylic acid
show 28 more
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
dicarboxylic acid monoester, dipeptide (CHEBI:4784)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Inhibitor
General Function
Zinc ion binding
Specific Function
Converts angiotensin I to angiotensin II by release of the terminal His-Leu, this results in an increase of the vasoconstrictor activity of angiotensin. Also able to inactivate bradykinin, a potent...
Gene Name
ACE
Uniprot ID
P12821
Uniprot Name
Angiotensin-converting enzyme
Molecular Weight
149713.675 Da
References
  1. Andujar-Sanchez M, Jara-Perez V, Camara-Artigas A: Thermodynamic determination of the binding constants of angiotensin-converting enzyme inhibitors by a displacement method. FEBS Lett. 2007 Jul 24;581(18):3449-54. Epub 2007 Jun 27. [PubMed:17618628]
  2. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
  3. Liu YH, Liu LY, Wu JX, Chen SX, Sun YX: Comparison of captopril and enalapril to study the role of the sulfhydryl-group in improvement of endothelial dysfunction with ACE inhibitors in high dieted methionine mice. J Cardiovasc Pharmacol. 2006 Jan;47(1):82-8. [PubMed:16424790]
  4. Natesh R, Schwager SL, Evans HR, Sturrock ED, Acharya KR: Structural details on the binding of antihypertensive drugs captopril and enalaprilat to human testicular angiotensin I-converting enzyme. Biochemistry. 2004 Jul 13;43(27):8718-24. [PubMed:15236580]

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. 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. Takara K, Kakumoto M, Tanigawara Y, Funakoshi J, Sakaeda T, Okumura K: Interaction of digoxin with antihypertensive drugs via MDR1. Life Sci. 2002 Feb 15;70(13):1491-500. [PubMed:11895100]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
Inhibitor
General Function
Proton-dependent oligopeptide secondary active transmembrane transporter activity
Specific Function
Proton-coupled intake of oligopeptides of 2 to 4 amino acids with a preference for dipeptides. May constitute a major route for the absorption of protein digestion end-products.
Gene Name
SLC15A1
Uniprot ID
P46059
Uniprot Name
Solute carrier family 15 member 1
Molecular Weight
78805.265 Da
References
  1. Han H, de Vrueh RL, Rhie JK, Covitz KM, Smith PL, Lee CP, Oh DM, Sadee W, Amidon GL: 5'-Amino acid esters of antiviral nucleosides, acyclovir, and AZT are absorbed by the intestinal PEPT1 peptide transporter. Pharm Res. 1998 Aug;15(8):1154-9. [PubMed:9706043]
  2. Han HK, Rhie JK, Oh DM, Saito G, Hsu CP, Stewart BH, Amidon GL: CHO/hPEPT1 cells overexpressing the human peptide transporter (hPEPT1) as an alternative in vitro model for peptidomimetic drugs. J Pharm Sci. 1999 Mar;88(3):347-50. [PubMed:10052994]
  3. Temple CS, Boyd CA: Proton-coupled oligopeptide transport by rat renal cortical brush border membrane vesicles: a functional analysis using ACE inhibitors to determine the isoform of the transporter. Biochim Biophys Acta. 1998 Aug 14;1373(1):277-81. [PubMed:9733984]
  4. Tsuji A: Transporter-mediated Drug Interactions. Drug Metab Pharmacokinet. 2002;17(4):253-74. [PubMed:15618677]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Involved in the renal elimination of endogenous and exogenous organic anions. Functions as organic anion exchanger when the uptake of one molecule of organic anion is coupled with an efflux of one ...
Gene Name
SLC22A6
Uniprot ID
Q4U2R8
Uniprot Name
Solute carrier family 22 member 6
Molecular Weight
61815.78 Da
References
  1. Kuze K, Graves P, Leahy A, Wilson P, Stuhlmann H, You G: Heterologous expression and functional characterization of a mouse renal organic anion transporter in mammalian cells. J Biol Chem. 1999 Jan 15;274(3):1519-24. [PubMed:9880528]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Plays an important role in the excretion/detoxification of endogenous and exogenous organic anions, especially from the brain and kidney. Involved in the transport basolateral of steviol, fexofenad...
Gene Name
SLC22A8
Uniprot ID
Q8TCC7
Uniprot Name
Solute carrier family 22 member 8
Molecular Weight
59855.585 Da
References
  1. Kobayashi Y, Ohshiro N, Tsuchiya A, Kohyama N, Ohbayashi M, Yamamoto T: Renal transport of organic compounds mediated by mouse organic anion transporter 3 (mOat3): further substrate specificity of mOat3. Drug Metab Dispos. 2004 May;32(5):479-83. [PubMed:15100168]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Mediates sodium-independent multispecific organic anion transport. Transport of prostaglandin E2, prostaglandin F2, tetracycline, bumetanide, estrone sulfate, glutarate, dehydroepiandrosterone sulf...
Gene Name
SLC22A7
Uniprot ID
Q9Y694
Uniprot Name
Solute carrier family 22 member 7
Molecular Weight
60025.025 Da
References
  1. Kobayashi Y, Ohshiro N, Shibusawa A, Sasaki T, Tokuyama S, Sekine T, Endou H, Yamamoto T: Isolation, characterization and differential gene expression of multispecific organic anion transporter 2 in mice. Mol Pharmacol. 2002 Jul;62(1):7-14. [PubMed:12065749]
  2. Sekine T, Cha SH, Tsuda M, Apiwattanakul N, Nakajima N, Kanai Y, Endou H: Identification of multispecific organic anion transporter 2 expressed predominantly in the liver. FEBS Lett. 1998 Jun 12;429(2):179-82. [PubMed:9650585]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Substrate
General Function
Sodium-independent organic anion transmembrane transporter activity
Specific Function
Mediates the Na(+)-independent transport of organic anions such as sulfobromophthalein (BSP) and conjugated (taurocholate) and unconjugated (cholate) bile acids (By similarity). Selectively inhibit...
Gene Name
SLCO1A2
Uniprot ID
P46721
Uniprot Name
Solute carrier organic anion transporter family member 1A2
Molecular Weight
74144.105 Da
References
  1. Abu-Zahra TN, Wolkoff AW, Kim RB, Pang KS: Uptake of enalapril and expression of organic anion transporting polypeptide 1 in zonal, isolated rat hepatocytes. Drug Metab Dispos. 2000 Jul;28(7):801-6. [PubMed:10859154]
  2. Pang KS, Wang PJ, Chung AY, Wolkoff AW: The modified dipeptide, enalapril, an angiotensin-converting enzyme inhibitor, is transported by the rat liver organic anion transport protein. Hepatology. 1998 Nov;28(5):1341-6. [PubMed:9794920]

Drug created on June 13, 2005 07:24 / Updated on November 16, 2018 08:03