U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ABSOLUTE
Molecular Formula C21H31N3O5
Molecular Weight 405.4888
Optical Activity UNSPECIFIED
Defined Stereocenters 3 / 3
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of LISINOPRIL ANHYDROUS

SMILES

c1ccc(cc1)CC[C@@]([H])(C(=O)O)N[C@@]([H])(CCCCN)C(=O)N2CCC[C@@]2([H])C(=O)O

InChI

InChIKey=RLAWWYSOJDYHDC-BZSNNMDCSA-N
InChI=1S/C21H31N3O5/c22-13-5-4-9-16(19(25)24-14-6-10-18(24)21(28)29)23-17(20(26)27)12-11-15-7-2-1-3-8-15/h1-3,7-8,16-18,23H,4-6,9-14,22H2,(H,26,27)(H,28,29)/t16-,17-,18-/m0/s1

HIDE SMILES / InChI
Lisinopril is a potent, competitive inhibitor of angiotensin-converting enzyme (ACE). Lisinopril is marketed under the brand name ZESTRIL. ZESTRIL is indicated for the treatment of hypertension. It may be used alone as initial therapy or concomitantly with other classes of antihypertensive agents. It is also indicated as adjunctive therapy in the management of heart failure in patients who are not responding adequately to diuretics and digitalis. Lisinopril inhibits angiotensin-converting enzyme (ACE) in human subjects and animals. ACE is a peptidyl dipeptidase that catalyzes the conversion of angiotensin I to the vasoconstrictor substance, angiotensin II. Angiotensin II also stimulates aldosterone secretion by the adrenal cortex. The beneficial effects of lisinopril in hypertension and heart failure appear to result primarily from suppression of the renin-angiotensin-aldosterone system. Inhibition of ACE results in decreased plasma angiotensin II which leads to decreased vasopressor activity and to decreased aldosterone secretion. While the mechanism through which ZESTRIL lowers blood pressure is believed to be primarily suppression of the renin-angiotensin-aldosterone system, ZESTRIL is antihypertensive even in patients with low-renin hypertension.

Originator

Curator's Comment:: # Merck

Approval Year

TargetsConditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
ZESTRIL

Approved Use

INDICATIONS & USAGE Hypertension Lisinopril tablets USP are indicated for the treatment of hypertension to lower blood pressure. Lowering blood pressure lowers the risk of fatal and non-fatal cardiovascular events, primarily strokes and myocardial infarctions. These benefits have been seen in controlled trials of antihypertensive drugs from a wide variety of pharmacologic classes including lisinopril. Control of high blood pressure should be part of comprehensive cardiovascular risk management, including, as appropriate, lipid control, diabetes management, antithrombotic therapy, smoking cessation, exercise, and limited sodium intake. Many patients will require more than 1 drug to achieve blood pressure goals. For specific advice on goals and management, see published guidelines, such as those of the National High Blood Pressure Education ProgramJoint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC). Numerous antihypertensive drugs, from a variety of pharmacologic classes and with different mechanisms of action, have been shown in randomized controlled trials to reduce cardiovascular morbidity and mortality, and it can be concluded that it is blood pressure reduction, and not some other pharmacologic property of the drugs, that is largely responsible for those benefits. The largest and most consistent cardiovascular outcome benefit has been a reduction in the risk of stroke, but reductions in myocardial infarction and cardiovascular mortality also have been seen regularly. Elevated systolic or diastolic pressure causes increased cardiovascular risk, and the absolute risk increase per mmHg is greater at higher blood pressures, so that even modest reductions of severe hypertension can provide substantial benefit. Relative risk reduction from blood pressure reduction is similar across populations with varying absolute risk, so the absolute benefit is greater in patients who are at higher risk independent of their hypertension (for example, patients with diabetes or hyperlipidemia), and such patients would be expected to benefit from more aggressive treatment to a lower blood pressure goal. Some antihypertensive drugs have smaller blood pressure effects (as monotherapy) in Black patients, and many antihypertensive drugs have additional approved indications and effects (e.g., on angina, heart failure, or diabetic kidney disease). These considerations may guide selection of therapy. Lisinopril tablets USP may be administered alone or with other antihypertensive agents. Heart Failure Lisinopril tablets USP are indicated as adjunctive therapy in the management of heart failure in patients who are not responding adequately to diuretics and digitalis. Acute Myocardial Infarction Lisinopril tablets USP are indicated for the treatment of hemodynamically stable patients within 24 hours of acute myocardial infarction, to improve survival. Patients should receive, as appropriate, the standard recommended treatments such as thrombolytics, aspirin and beta-blockers. In using lisinopril tablets USP, consideration should be given to the fact that another angiotensin-converting enzyme inhibitor, captopril, has caused agranulocytosis, particularly in patients with renal impairment or collagen vascular disease, and that available data are insufficient to show that lisinopril tablets USP do not have a similar risk (seeWARNINGS). In considering the use of lisinopril tablets USP, it should be noted that in controlled clinical trials, ACE inhibitors have an effect on blood pressure that is less in Black patients than in non-Blacks. In addition, ACE inhibitors have been associated with a higher rate of angioedema in Black than in non-Black patients (seeWARNINGS, Anaphylactoid and Possibly Related Reactions).

Launch Date

5.6773437E11
Primary
ZESTRIL

Approved Use

Hypertension ZESTRIL is indicated for the treatment of hypertension. It may be used alone as initial therapy or concomitantly with other classes of antihypertensive agents. Heart Failure ZESTRIL is indicated as adjunctive therapy in the management of heart failure in patients who are not responding adequately to diuretics and digitalis. Acute Myocardial Infarction ZESTRIL is indicated for the treatment of hemodynamically stable patients within 24 hours of acute myocardial infarction, to improve survival. Patients should receive, as appropriate, the standard recommended treatments such as thrombolytics, aspirin and beta-blockers.

Launch Date

5.6773437E11
Primary
ZESTRIL

Approved Use

Hypertension ZESTRIL is indicated for the treatment of hypertension. It may be used alone as initial therapy or concomitantly with other classes of antihypertensive agents. Heart Failure ZESTRIL is indicated as adjunctive therapy in the management of heart failure in patients who are not responding adequately to diuretics and digitalis. Acute Myocardial Infarction ZESTRIL is indicated for the treatment of hemodynamically stable patients within 24 hours of acute myocardial infarction, to improve survival. Patients should receive, as appropriate, the standard recommended treatments such as thrombolytics, aspirin and beta-blockers.

Launch Date

5.6773437E11
Sourcing

Sourcing

Vendor/AggregatorIDURL
PubMed

PubMed

TitleDatePubMed
[Antihypertensive effect of enalapril and lisinopril administered in combination with nonsteroid anti-inflammatory agents].
2001
Telmisartan: a review of its use in hypertension.
2001
Effects of lisinopril on streptozotocin-induced diabetic neuropathy in rats.
2001 Apr
Circulating plasma vascular endothelial growth factor and microvascular complications of type 1 diabetes mellitus: the influence of ACE inhibition.
2001 Apr
The influence of dose of angiotensin I-converting enzyme inhibitor on systolic blood pressure variability in heart failure: a substudy of the Assessment of Treatment with Lisinopril and Survival in heart failure (ATLAS) trial.
2001 Apr
Characterization of bovine atrial angiotensin-converting enzyme.
2001 Apr
Neurovascular interactions between aldose reductase and angiotensin-converting enzyme inhibition in diabetic rats.
2001 Apr 13
The effects of C-type natriuretic peptide on catecholamine release in the pacific spiny dogfish (Squalus acanthias).
2001 Aug
Angiotensin-converting enzyme degrades Alzheimer amyloid beta-peptide (A beta ); retards A beta aggregation, deposition, fibril formation; and inhibits cytotoxicity.
2001 Dec 21
[Clinical study of the month. The CALM study assessing the combination of an angiotensin-converting enzyme inhibitor and an angiotensin II receptor antagonist in the treatment of diabetic nephropathy].
2001 Feb
Protective effect of lisinopril against ischemia-reperfusion injury in isolated guinea pig hearts.
2001 Feb
Lisinopril shows regression of myocardial fibrosis in patients with hypertensive heart disease.
2001 Feb-Mar
Fluorescence polarization studies of different forms of angiotensin-converting enzyme.
2001 Jul
Does the antihypertensive response to angiotensin converting enzyme inhibition predict the antihypertensive response to angiotensin receptor antagonism?
2001 Jul
Better microvascular function on long-term treatment with lisinopril than with nifedipine in renal transplant recipients.
2001 Jul
Characterization of angiotensin-converting enzyme in canine testis.
2001 Jul
Sternal dehiscence after cardiac surgery and ACE inhibitors [correction of ACE type 1 inhibition].
2001 Jul
Lisinopril improves endothelial function in chronic cigarette smokers.
2001 Jul
Multiple pathways of angiotensin I conversion and their functional role in the canine penile corpus cavernosum.
2001 Jul
Spectrophotometric and HPTLC-densitometric determination of lisinopril and hydrochlorothiazide in binary mixtures.
2001 Jul
Spectrophotometric, septrofluorimetric and LC determination of lisinopril.
2001 Jul
The quantitative determination of several inhibitors of the angiotensin-converting enzyme by CE.
2001 Jul
Reduction of left ventricular mass by lisinopril and nifedipine in hypertensive renal transplant recipients: a prospective randomized double-blind study.
2001 Jul 15
Simultaneous determination of hydrochlorothiazide and several inhibitors of angiotensin-converting enzyme by capillary electrophoresis.
2001 Jul 27
Possible roles of cardiac chymase after myocardial infarction in hamster hearts.
2001 Jun
ACE inhibition or angiotensin receptor blockade: impact on potassium in renal failure.
2001 Jun
A health perception score predicts cardiac events in patients with heart failure: results from the IMPRESS trial.
2001 Jun
Effects of various antihypertensive drugs on the function of osteoblast.
2001 Jun
Cardioprotective effect of propranolol from alcohol-induced heart muscle damage as assessed by plasma cardiac troponin-t.
2001 Jun
Possible interaction of clozapine and lisinopril.
2001 Jun
Pulse methylprednisolone, cyclosporine, and ace inhibitor therapy decreases proteinuria in two siblings with familial focal segmental glomerulosclerosis.
2001 Jun
Add-on angiotensin receptor blockade with maximized ACE inhibition.
2001 Jun
Dobutamine as bridge to angiotensin-converting enzyme inhibitor-nitrate therapy in endstage heart failure.
2001 Mar
Angioedema and antihypertensive therapy.
2001 Mar 15
[Therapeutic perspectives: association of ACE inhibitors and angiotensin receptor blockers].
2001 Mar-Apr
Update in pharmacologic treatment of hypertension.
2001 May
Trapped renal arteries: functional renal artery stenosis due to occlusion of the aorta in the arch and below the kidneys.
2001 May
Effect of antihypertensive therapy on renal artery structure in type 2 diabetic rats with hypertension.
2001 May
Lisinopril reduces albuminuria during exercise in low grade microalbuminuric type 1 diabetic patients: a double blind randomized study.
2001 May
RXP 407, a selective inhibitor of the N-domain of angiotensin I-converting enzyme, blocks in vivo the degradation of hemoregulatory peptide acetyl-Ser-Asp-Lys-Pro with no effect on angiotensin I hydrolysis.
2001 May
Neurohormonal activation, the renal dopaminergic system and sodium handling in patients with severe heart failure under vasodilator therapy.
2001 May
Effect of column temperature on the behaviour of some angiotensin converting enzyme inhibitors during high-performance liquid chromatographic analysis.
2001 May 5
Renal tubular peptide catabolism in chronic vascular rejection.
2001 May-Jul
Prescribing patterns and cost of antihypertensive drugs in an internal medicine clinic.
2001 May-Jun
A prospective comparison of four antihypertensive agents in daily clinical practice.
2001 May-Jun
Pet ownership, but not ace inhibitor therapy, blunts home blood pressure responses to mental stress.
2001 Oct
Differential manipulation of the renin angiotensin system and epoietin requirements in maintenance haemodialysis patients.
2001 Sep
Angiotensin-converting enzyme inhibition induces apoptosis in erythroid precursors and affects insulin-like growth factor-1 in posttransplantation erythrocytosis.
2001 Sep
Impact of postprandial hypertriglyceridemia on vascular responses in patients with coronary artery disease: effects of ACE inhibitors and fibrates.
2001 Sep
Cardiovascular critical event pathways for the progression of heart failure; a report from the ATLAS study.
2001 Sep
Patents

Sample Use Guides

Usual Adult Dose for Hypertension Initial dose: 10 mg orally once a day; 5 mg orally once a day Maintenance dose: 20 to 40 mg orally once a day Maximum dose: 80 mg orally once a day Usual Adult Dose for Congestive Heart Failure Initial dose: 2.5 to 5 mg orally once a day Maintenance dose: Dosage should be increased as tolerated Maximum dose: 40 mg orally once a day Usual Adult Dose for Myocardial Infarction Initial dose: 5 mg orally (within 24 hours of the onset of acute myocardial infarction) Subsequent doses: 5 mg orally after 24 hours, then 10 mg orally after 48 hours. Maintenance dose: 10 mg orally once a day. Dosing should continue for at least 6 weeks.
Route of Administration: Oral
In Vitro Use Guide
Lisinopril inhibited angiotensin converting enzyme from sheep serum with IC50 5.6 nM
Name Type Language
LISINOPRIL ANHYDROUS
Common Name English
LISINOPRIL [INN]
Common Name English
L-PROLINE, 1-(N(SUP 2)-(1-CARBOXY-3-PHENYLPROPYL)-L-LYSYL)-
Common Name English
LISINOPRIL [WHO-DD]
Common Name English
1-(N(SUP 2)-((S)-1-CARBOXY-3-PHENYLPROPYL)-L-LYSYL)-L-PROLINE
Systematic Name English
LISINOPRIL [MI]
Common Name English
Classification Tree Code System Code
NDF-RT N0000000181
Created by admin on Sat Jun 26 04:05:07 UTC 2021 , Edited by admin on Sat Jun 26 04:05:07 UTC 2021
WHO-ATC C09AA03
Created by admin on Sat Jun 26 04:05:07 UTC 2021 , Edited by admin on Sat Jun 26 04:05:07 UTC 2021
NCI_THESAURUS C247
Created by admin on Sat Jun 26 04:05:07 UTC 2021 , Edited by admin on Sat Jun 26 04:05:07 UTC 2021
NDF-RT N0000175562
Created by admin on Sat Jun 26 04:05:07 UTC 2021 , Edited by admin on Sat Jun 26 04:05:07 UTC 2021
Code System Code Type Description
HSDB
6852
Created by admin on Sat Jun 26 04:05:07 UTC 2021 , Edited by admin on Sat Jun 26 04:05:07 UTC 2021
PRIMARY
EVMPD
SUB08533MIG
Created by admin on Sat Jun 26 04:05:07 UTC 2021 , Edited by admin on Sat Jun 26 04:05:07 UTC 2021
PRIMARY
EVMPD
SUB23348
Created by admin on Sat Jun 26 04:05:07 UTC 2021 , Edited by admin on Sat Jun 26 04:05:07 UTC 2021
PRIMARY
PUBCHEM
5362119
Created by admin on Sat Jun 26 04:05:07 UTC 2021 , Edited by admin on Sat Jun 26 04:05:07 UTC 2021
PRIMARY
MERCK INDEX
M6842
Created by admin on Sat Jun 26 04:05:07 UTC 2021 , Edited by admin on Sat Jun 26 04:05:07 UTC 2021
PRIMARY Merck Index
ECHA (EC/EINECS)
278-488-1
Created by admin on Sat Jun 26 04:05:07 UTC 2021 , Edited by admin on Sat Jun 26 04:05:07 UTC 2021
PRIMARY
RXCUI
1546022
Created by admin on Sat Jun 26 04:05:07 UTC 2021 , Edited by admin on Sat Jun 26 04:05:07 UTC 2021
PRIMARY RxNorm
CAS
76547-98-3
Created by admin on Sat Jun 26 04:05:07 UTC 2021 , Edited by admin on Sat Jun 26 04:05:07 UTC 2021
PRIMARY
EPA CompTox
76547-98-3
Created by admin on Sat Jun 26 04:05:07 UTC 2021 , Edited by admin on Sat Jun 26 04:05:07 UTC 2021
PRIMARY
NCI_THESAURUS
C83924
Created by admin on Sat Jun 26 04:05:07 UTC 2021 , Edited by admin on Sat Jun 26 04:05:07 UTC 2021
PRIMARY
FDA UNII
7Q3P4BS2FD
Created by admin on Sat Jun 26 04:05:07 UTC 2021 , Edited by admin on Sat Jun 26 04:05:07 UTC 2021
PRIMARY
INN
5425
Created by admin on Sat Jun 26 04:05:07 UTC 2021 , Edited by admin on Sat Jun 26 04:05:07 UTC 2021
PRIMARY