General
Preferred name
enalapril
Synonyms
ENALAPRIL MALEATE ()
Enalapril (D5 maleate) ()
MK-421 (D5 maleate) ()
MK-421 ()
MK-421 (maleate) ()
MK-421 Maleate ()
Renitec Maleate ()
Glioten Maleate ()
Vasotec Maleate ()
MK-421 (maleate)MK-421 Maleate ()
Enalapril (maleate) ()
QGC-011 ()
Innovace ()
Pralenal 10 ()
Epaned kit ()
Ednyt ()
Renitec ()
Pralenal 5 ()
Pralenal 2.5 ()
Enapren ()
Pralenal 20 ()
Epaned ()
Vasotec ()
Xanef ()
NSC-758143 ()
Vaseretic ()
Lexxel ()
C09AA02 ()
Olinapril ()
Enalapril-d5 (maleate) ()
P&D ID
PD009906
CAS
76095-16-4
75847-73-3
76420-75-2
349554-02-5
Tags
prodrug
natural product
drug
available
Approved by
FDA
First approval
1985
Drug Status
approved
vet_approved
Drug indication
Hypertension
Antihypertensive
Max Phase
Phase 4
Probe control
Probe control not defined
Orthogonal probes
0
No orthogonal probes found
Similar probes
0
No structurally similar probes found
Structure
P&D probe-likeness score
Structure formats
[[ format ]]
[[ compound[format === 'MOL' ? 'molblock' : format.toLowerCase()] ]]
Description
(extracted from source data)
INDICATION
Indicated for the management of essential or renovascular hypertension [L6586] as monotherapy or in combination with other antihypertensive agents, such as thiazide diuretics, for an additive effect.[label]; ; Indicated for the treatment of symptomatic congestive heart failure, usually in combination with diuretics and digitalis.[label]; ; Indicated for the management of asymptomatic left ventricular dysfunction in patients with an ejection fraction of ⤠to 35 percent to decrease the rate of development of overt heart failure and the incidence of hospitalization for heart failure.[label]
ROE
Enalapril is mainly eliminated through renal excretion, where approximately 94% of the total dose is excreted via urine or feces as either enalaprilat or unchanged parent compound.[label] About 61% and 33% of the total dose can be recovered in the urine and feces, respectively.[A179140] In the urine, about 40% of the recovered dose is in the form of enalaprilat.[label]
HALF-LIFE
The average terminal half life of enalaprilat is 35-38 hours. The effective half life following multiple doses is 11-14 hours. The prolonged terminal half-life is due to the binding of enalaprilat to ACE.[A179134]
METABOLISM
About 60% of the absorbed dose is extensively hydrolyzed to enalaprilat via de-esterification mediated by hepatic esterases.[label] In humans, metabolism beyond bioactivation to enalaprilat is not observed.[A179134]
ABSORPTION
Following oral administration, the peak plasma concentrations (Cmax) of enalapril is achieved within 1 hour post dosing while the Cmax of enalaprilat occurs at three to four hours post dosing.[label] The steady-state is achieved by the fourth daily dose and there is no accumulation with repeated dosing.[A179134] However, accumulation of enalaprilat may occur in patients with creatinine clearance less than 30 mL/min.[A179131] Food intake is reported to have a minimal effect on drug absorption.[A179119] Following oral administration, about 60% of enalapril was absorbed.[label] Bioavailability of enalapril averaged about 40% when intravenous enalaprilat was used as a reference standard.[A18459]
DESCRIPTION
Pro-drug for elanoprilat
(GtoPdb)
PHARMACODYNAMICS
Enalapril is an antihypertensive agent that exhibits natriuretic and uricosuric properties. Enalapril lowers blood pressure in all grades of essential and renovascular hypertension, and peripheral vascular resistance without causing an increase in heart rate.[A179137] Individuals with low-renin hypertensive population were still responsive to enalapril.[label] The duration of hypertensive effect in the systolic and diastolic blood pressure persists for at least 24 hours following initial administration of a single oral dose, and repeated daily administration of enalapril confers an additional reduction in blood pressure and a steady-state antihypertensive response may take several weeks.[A179140] In patients with severe congestive heart failure and inadequate clinical response to conventional antihypertensive therapies, treatment with enalapril resulted in improvements in cardiac performance as observed by a reduction in both preload and afterload, and improved clinical status long-term.[A179137] Furthermore, enalapril was shown to increase cardiac output and stroke volume while decreasing pulmonary capillary wedge pressure in patients with congestive heart failure refractory to conventional treatment with digitalis and diuretics. In clinical studies, enalapril reduced left ventricular mass, and did not affect cardiac function or myocardial perfusion during exercise.[A179134] Enalapril is not highly associated with the risk of bradycardia unlike most diuretics and beta-blockers [A179137] and it does not produce rebound hypertension upon discontinuation of therapy.[A179134] ; ; Enalapril is not reported to produce hypokalaemia, hyperglycaemia, hyperuricaemia or hypercholesterolaemia. In the kidneys, enalapril was shown to increase renal blood flow and decrease renal vascular resistance. It also augmented the glomerular filtration rate in patients with a glomerular filtration rate less than 80 mL/min.[A179134] When used in combination, enalapril was shown to attenuate the extent of drug-induced hypokalemia caused by hydrochlorothiazide [A179137] and the antihypertensive effects of both drugs were potentiated.[A18459]
TOXICITY
**LD50 and Overdose**; ; Oral LD50 in rats is 2973 mg/kg.[MSDS] Lethality was observed with single oral doses of enalapril above 1000 mg/kg in mice and greater than or equal to 1775 mg/kg in rats. Serum enalaprilat levels 100- and 200-fold higher than usually seen after therapeutic doses have been reported after ingestion of 300 mg and 440 mg of enalapril, respectively.[L6586] While there is limited data about enalapril overdose in humans, overdosage may result in marked hypotension and stupor based on the pharmacological properties of the drug. Most common adverse effects of enalapril include cough, hypotension, stupor, headache, dizziness and fatigue. If hypotension is seen, usual treatment of intravenous infusion of normal saline solution is recommended. Enalaprilat may be removed from systemic circulation with the use of hemodialysis. It has been removed from neonatal circulation by peritoneal dialysis.[label]; ; **Nonclinical toxicology**; ; Maternal and fetal toxicity occudred in some rabbits treated with enalapril at doses of 1 mg/kg/day or more. There was no fetotoxicity, expressed as a decrease in average fetal weight, or teratogenicity in rats treated with enalapril at doses up to 200 mg/kg/day, which is about 333 times the maximum human dose.[L6586] In mice and rats receiving enalapril at doses ranging from 90 to 180 mg/kg/day, there was no evidence of a tumorigenic effect. Neither enalapril or its active metabolite were shown to be mutagenic or genotoxic in _in vitro_ and _in vivo_ studies. There were no adverse effects on reproductive performance of male and female rats treated with up to 90 mg/kg/day of enalapril. [label]; ; **Use in special populations**; ; Caution is warranted in patients who are concurrently using another ACE inhibitors with enalapril, as there have been incidences of agranulocytosis with the use of captopril, which is another ACE inhibitor. This adverse event may be particularly significant in patients with renal impairment or collagen vascular disease.[label] As enalapril and enalaprilat were shown to be secreted in human milk in trace amounts, the use of enalaprilat in nursing women is not recommended.[L6586] Significant fetal transfer occurs with enalapril and enalaprilat thus the use of the drug in pregnant women should be strongly avoided. Caution is advised when enalapril is used in patients who are elderly or with renal impairment, as dosage adjustments may be appropriate. The antihypertensive effect of angiotensin converting enzyme inhibitors is generally lower in individuals of African descent, usually a low-renin hypertensive population.[label]
DESCRIPTION
Enalapril is an angiotensin converting enzyme (ACE) inhibitor used in the treatment of hypertension, congestive heart failure, myocardial infarction, and diabetic nephropathies. Its IC50 values range from 2 to 800 nM. lt belongs to a class of medications called angiotensin converting enzyme inhibitors. pressure. lt decreases levels of angiotensin II leading to less vasoconstriction and decreased blood pressure by inhibiting ACE. lt has been shown to lower the death rate in systolic heart failure. It is on the World Health Organization's List of Essential Medicines, the most important medications needed in a basic health system.
(BOC Sciences Bioactive Compounds)
[[ p.pathway_name ]]
[[ compound.targets[tid].gene_name ]]
Compound Sets
20
BOC Sciences Bioactive Compounds
ChEMBL Approved Drugs
ChEMBL Drugs
Drug Repurposing Hub
DrugBank
DrugBank Approved Drugs
DrugCentral
DrugCentral Approved Drugs
DrugMAP
DrugMAP Approved Drugs
Guide to Pharmacology
LSP-MoA library (Laboratory of Systems Pharmacology)
MedChem Express Bioactive Compound Library
NPC Screening Collection
Prestwick Chemical Library
ReFrame library
Selleckchem Bioactive Compound Library
TargetMol Bioactive Compound Library
The Spectrum Collection
[[ a.name ]]
[[ ligand_id ]]
free of charge
External IDs
76
Molecular Weight
376.2
Hydrogen Bond Acceptors
5
Hydrogen Bond Donors
2
Rotatable Bonds
9
Ring Count
2
Aromatic Ring Count
1
cLogP
1.6
TPSA
95.94
Fraction CSP3
0.55
Chiral centers
3.0
Largest ring
6.0
QED
0.64
Structural alerts
0
No structural alerts detected
Related compounds
Custom attributes
(extracted from source data)
Target
Angiotensin-converting Enzyme (ACE)
ACE
ACE,RAAS
Pathway
Metabolic Enzyme/Protease
Endocrinology/Hormones
Indication
hypertension, congestive heart failure, left ventricular systolic dysfunction (LVSD)
MOA
angiotensin converting enzyme inhibitor
Therapeutic Class
Antihypertensive Agents
Solubility
DMSO 99 mg/mL
Water <1 mg/mL
Source data
