Banner
targets (2) transporters (2)
for drugs
Identification
Name Lisinopril
Accession Number DB00722 (APRD00560)
Type small molecule
Groups approved
Description

Lisinopril is a potent, competitive inhibitor of angiotensin-converting enzyme (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). Lisinopril may be used to treat hypertension and symptomatic congestive heart failure, to improve survival in certain individuals following myocardial infarction, and to prevent progression of renal disease in hypertensive patients with diabetes mellitus and microalbuminuria or overt nephropathy.
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms Not Available
Salts Not Available
Brand names
Name Company
Acercomp AstraZeneca/Promed
Inhibril
Linopril Klinger (Brazil)
Lisinopril Dihydrate
Lisipril Hexal (Czech Republic), Orion (Finland)
Lysinopril
Noperten Dexa (Indonesia)
Presiten
Prinivil Merck Frosst
Sinopril Eczacibasi (Russia)
Zestril AstraZeneca
First Prev Next Last
Brand mixtures
Brand Name Ingredients
Lisinopril Comp lisinopril + hydrochlorothiazide
Prinzide lisinopril + hydrochlorothiazide
Zestoretic Tab 10/12.5mg lisinopril + hydrochlorothiazide
Zestoretic Tab 20/12.5mg lisinopril + hydrochlorothiazide
Zestoretic Tab 20/25mg lisinopril + hydrochlorothiazide
Categories
  • Antihypertensive Agents
  • Angiotensin-converting Enzyme Inhibitors
CAS number 83915-83-7
Weight Average: 405.4879
Monoisotopic: 405.226371117
Chemical Formula C21H31N3O5
InChI Key InChIKey=RLAWWYSOJDYHDC-BZSNNMDCSA-N
InChI
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
Plain Text
IUPAC Name
(2S)-1-[(2S)-6-amino-2-{[(1S)-1-carboxy-3-phenylpropyl]amino}hexanoyl]pyrrolidine-2-carboxylic acid
SMILES
NCCCC[C@H](N[C@@H](CCC1=CC=CC=C1)C(O)=O)C(=O)N1CCC[C@H]1C(O)=O
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Polypeptides
  • Phenylpropylamines
Substructures
  • Hydroxy Compounds
  • Acetates
  • Aliphatic and Aryl Amines
  • Amino Ketones
  • Pyrrolidines
  • Benzene and Derivatives
  • Carboxylic Acids and Derivatives
  • Polypeptides
  • Heterocyclic compounds
  • Aromatic compounds
  • Carboxamides and Derivatives
  • Phenylpropylamines
  • Amino Acids
Pharmacology
Indication For the treatment of hypertension and symptomatic congestive heart failure. May be used in conjunction with thrombolytic agents, aspirin and/or β-blockers to improve survival in hemodynamically stable individuals following myocardial infarction. May be used to slow the progression of renal disease in hypertensive patients with diabetes mellitus and microalbuminuria or overt nephropathy.
Pharmacodynamics Lisinopril is an orally active ACE inhibitor that antagonizes 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 further sustain the effects of lisinopril 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. Lisinopril, one of the few ACE inhibitors that is not a prodrug, 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. Lisinopril 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.
Absorption Approximately 25%, but widely variable between individuals (6 to 60%) in all doses tested (5-80 mg); absorption is unaffected by food
Volume of distribution Not Available
Protein binding Lisinopril does not appear to be bound to serum proteins other than ACE.
Metabolism Does not undergo metabolism, excreted unchanged in urine.
Route of elimination Lisinopril does not undergo metabolism and is excreted unchanged entirely in the urine.
Half life Effective half life of accumulation following multiple dosing is 12 hours.
Clearance
  • 10 L/h [child weighting 30 kg receiving doses of 0.1 to 0.2 mg/kg]
Toxicity Symptoms of overdose include severe hypotension, electrolyte disturbances, and renal failure. LD50= 2000 mg/kg(orally in rat). Most frequent adverse effects include headache, dizziness, cough, fatigue and diarrhea.
Affected organisms
  • Humans and other mammals
Pathways
Pathway Name SMPDB ID
Smp00150 Lisinopril Pathway SMP00150
Pharmacoeconomics
Manufacturers
  • Actavis elizabeth llc
  • Apotex inc etobicoke site
  • Aurobindo pharma ltd
  • Ivax pharmaceuticals inc sub teva pharmaceuticals usa
  • Lek pharmaceuticals d d
  • Lupin ltd
  • Mylan pharmaceuticals inc
  • Ranbaxy pharmaceuticals inc
  • Sandoz inc
  • Teva pharmaceuticals usa inc
  • Vintage pharmaceuticals llc
  • Watson laboratories inc
  • West ward pharmaceutical corp
  • Wockhardt ltd
  • Merck research laboratories div merck co inc
  • Astrazeneca uk ltd
Packagers
Dosage forms
Form Route Strength
Tablet Oral 10 mg
Tablet Oral 2.5 mg
Tablet Oral 20 mg
Tablet Oral 30 mg
Tablet Oral 40 mg
Tablet Oral 5 mg
Prices
Unit description Cost Unit
Prinivil 90 20 mg tablet Bottle 111.71 USD bottle
Prinzide 30 20-12.5 mg tablet Bottle 45.99 USD bottle
Prinivil 30 2.5 mg tablet Bottle 22.48 USD bottle
Lisinopril 100% powder 21.6 USD g
Zestril 40 mg tablet 2.53 USD tablet
Zestril 30 mg tablet 2.41 USD tablet
Prinivil 40 mg tablet 2.23 USD tablet
Zestoretic 20-25 mg tablet 2.01 USD tablet
Zestoretic 20-12.5 mg tablet 2.0 USD tablet
Prinzide 20-25 mg tablet 1.98 USD tablet
Zestoretic 10-12.5 mg tablet 1.89 USD tablet
Zestoretic 10-12.5 tablet 1.75 USD tablet
Lisinopril 30 mg tablet 1.53 USD tablet
Lisinopril 40 mg tablet 1.44 USD tablet
Prinzide 20-12.5 mg tablet 1.38 USD tablet
Prinzide 10-12.5 mg tablet 1.37 USD tablet
Zestril 20 mg tablet 1.37 USD tablet
Zestril 10 mg tablet 1.33 USD tablet
Zestoretic 20-25 tablet 1.28 USD tablet
Zestril 5 mg tablet 1.28 USD tablet
Zestoretic 20-12.5 tablet 1.26 USD tablet
Lisinopril 20 mg tablet 1.09 USD tablet
Prinivil 20 mg tablet 1.05 USD tablet
Zestril 2.5 mg tablet 1.04 USD tablet
Lisinopril 10 mg tablet 1.01 USD tablet
Prinivil 10 mg tablet 1.01 USD tablet
Lisinopril 5 mg tablet 0.99 USD tablet
Prinivil 5 mg tablet 0.96 USD tablet
Apo-Lisinopril 20 mg Tablet 0.71 USD tablet
Co Lisinopril 20 mg Tablet 0.71 USD tablet
Mylan-Lisinopril 20 mg Tablet 0.71 USD tablet
Novo-Lisinopril (Type P) 20 mg Tablet 0.71 USD tablet
Novo-Lisinopril (Type Z) 20 mg Tablet 0.71 USD tablet
Pms-Lisinopril 20 mg Tablet 0.71 USD tablet
Ran-Lisinopril 20 mg Tablet 0.71 USD tablet
Ratio-Lisinopril P 20 mg Tablet 0.71 USD tablet
Ratio-Lisinopril Z 20 mg Tablet 0.71 USD tablet
Sandoz Lisinopril 20 mg Tablet 0.71 USD tablet
Lisinopril 2.5 mg tablet 0.65 USD tablet
Apo-Lisinopril 10 mg Tablet 0.59 USD tablet
Co Lisinopril 10 mg Tablet 0.59 USD tablet
Mylan-Lisinopril 10 mg Tablet 0.59 USD tablet
Novo-Lisinopril (Type P) 10 mg Tablet 0.59 USD tablet
Novo-Lisinopril (Type Z) 10 mg Tablet 0.59 USD tablet
Pms-Lisinopril 10 mg Tablet 0.59 USD tablet
Ran-Lisinopril 10 mg Tablet 0.59 USD tablet
Ratio-Lisinopril P 10 mg Tablet 0.59 USD tablet
Ratio-Lisinopril Z 10 mg Tablet 0.59 USD tablet
Sandoz Lisinopril 10 mg Tablet 0.59 USD tablet
Apo-Lisinopril 5 mg Tablet 0.49 USD tablet
Co Lisinopril 5 mg Tablet 0.49 USD tablet
Mylan-Lisinopril 5 mg Tablet 0.49 USD tablet
Novo-Lisinopril (Type P) 5 mg Tablet 0.49 USD tablet
Novo-Lisinopril (Type Z) 5 mg Tablet 0.49 USD tablet
Pms-Lisinopril 5 mg Tablet 0.49 USD tablet
Ran-Lisinopril 5 mg Tablet 0.49 USD tablet
Ratio-Lisinopril P 5 mg Tablet 0.49 USD tablet
Ratio-Lisinopril Z 5 mg Tablet 0.49 USD tablet
Sandoz Lisinopril 5 mg Tablet 0.49 USD tablet
First Prev Next Last
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents Not Available
Properties
State solid
Experimental Properties
Property Value Source
water solubility 9.7E+004 mg/L MERCK INDEX (1996)
logP -1.01 MERCK INDEX (1996); pH 7
pKa 2.5 (at 25 °C) MERCK INDEX (1996)
Predicted Properties
Property Value Source
water solubility 2.16e-01 g/l ALOGPS
logP -1.2 ALOGPS
logP -3.1 ChemAxon
logS -3.3 ALOGPS
pKa (strongest acidic) 3.17 ChemAxon
pKa (strongest basic) 10.21 ChemAxon
physiological charge 0 ChemAxon
hydrogen acceptor count 7 ChemAxon
hydrogen donor count 4 ChemAxon
polar surface area 132.96 ChemAxon
rotatable bond count 12 ChemAxon
refractivity 107.37 ChemAxon
polarizability 43.5 ChemAxon
References
Synthesis Reference Not Available
General Reference
  1. Abdelmalek MF, Douglas DD: Lisinopril-induced isolated visceral angioedema: review of ACE-inhibitor-induced small bowel angioedema. Dig Dis Sci. 1997 Apr;42(4):847-50. Pubmed
  2. Hasslacher C: Influence of the ACE inhibitor lisinopril on blood pressure, metabolism, and renal function parameter in hypertensive type II diabetic patients: a postmarketing surveillance study. J Diabetes Complications. 1996 May-Jun;10(3):136-8. Pubmed
  3. Nielsen SE, Sugaya T, Tarnow L, Lajer M, Schjoedt KJ, Astrup AS, Baba T, Parving HH, Rossing P: Tubular and glomerular injury in diabetes and the impact of ACE inhibition. Diabetes Care. 2009 Sep;32(9):1684-8. Epub 2009 Jun 5. Pubmed
  4. Patchett AA, Harris E, Tristram EW, Wyvratt MJ, Wu MT, Taub D, Peterson ER, Ikeler TJ, ten Broeke J, Payne LG, Ondeyka DL, Thorsett ED, Greenlee WJ, Lohr NS, Hoffsommer RD, Joshua H, Ruyle WV, Rothrock JW, Aster SD, Maycock AL, Robinson FM, Hirschmann R, Sweet CS, Ulm EH, Gross DM, Vassil TC, Stone CA: A new class of angiotensin-converting enzyme inhibitors. Nature. 1980 Nov 20;288(5788):280-3. Pubmed
External Links
Resource Link
KEGG Drug D00362 Link_out
PubChem Compound 5362119 Link_out
PubChem Substance 46504893 Link_out
ChemSpider 4514933 Link_out
ChEBI 43755 Link_out
ChEMBL 43755 Link_out
Therapeutic Targets Database DAP000587 Link_out
PharmGKB PA450242 Link_out
HET LPR Link_out
Drug Product Database 2217538 Link_out
RxList http://www.rxlist.com/cgi/generic/lisinop.htm Link_out
Drugs.com http://www.drugs.com/lisinopril.html Link_out
PDRhealth http://www.pdrhealth.com/drugs/rx/rx-mono.aspx?contentFileName=zes1498.html&contentName=Zestril&contentId=861 Link_out
Wikipedia http://en.wikipedia.org/wiki/Lisinopril Link_out
ATC Codes
  • C09AA03
AHFS Codes
  • 24:32.04
PDB Entries
FDA label show (267 KB)
MSDS Not Available
Interactions
Drug Interactions
Drug Interaction
Amiloride Increased risk of hyperkalemia
Drospirenone Increased risk of hyperkalemia
Lithium The ACE inhibitor increases serum levels of lithium
Potassium Increased risk of hyperkalemia
Spironolactone Increased risk of hyperkalemia
Tizanidine Tizanidine increases the risk of hypotension with the ACE inhibitor
Tobramycin Increased risk of nephrotoxicity
Treprostinil Additive hypotensive effect. Monitor antihypertensive therapy during concomitant use.
Triamterene Increased risk of hyperkalemia
Food Interactions
  • Herbs that may attenuate the antihypertensive effect of lisinopril include: bayberry, blue cohash, cayenne, ephedra, ginger, ginseng (American), kola and licorice.
  • High salt intake may attenuate the antihypertensive effect of lisinopril.
  • Lisinopril decreases the excretion of potassium. Salt substitutes containing potassium increase the risk of hyperkalemia.
  • Take without regard to meals.
Targets

1. Angiotensin-converting enzyme

Pharmacological action: yes
Actions: inhibitor

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 vasodilator

Organism class: human
UniProt ID: P12821 Link_out
Gene: ACE Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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
  2. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed
  3. Piepho RW: Overview of the angiotensin-converting-enzyme inhibitors. Am J Health Syst Pharm. 2000 Oct 1;57 Suppl 1:S3-7. Pubmed
  4. Song JC, White CM: Clinical pharmacokinetics and selective pharmacodynamics of new angiotensin converting enzyme inhibitors: an update. Clin Pharmacokinet. 2002;41(3):207-24. Pubmed
  5. Tellez-Sanz R, Garcia-Fuentes L, Baron C: Calorimetric analysis of lisinopril binding to angiotensin I-converting enzyme. FEBS Lett. 1998 Feb 13;423(1):75-80. Pubmed

2. Angiotensin-converting enzyme 2

Pharmacological action: yes
Actions: inhibitor

Carboxypeptidase which converts angiotensin I to angiotensin 1-9, a peptide of unknown function, and angiotensin II to angiotensin 1-7, a vasodilator. Also able to hydrolyze apelin- 13 and dynorphin-13 with high efficiency. May be an important regulator of heart function. In case of human coronaviruses SARS and HCoV-NL63 infections, serve as functional receptor for the spike glycoprotein of both coronaviruses

Organism class: human
UniProt ID: Q9BYF1 Link_out
Gene: ACE2 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Parish RC, Miller LJ: Adverse effects of angiotensin converting enzyme (ACE) inhibitors. An update. Drug Saf. 1992 Jan-Feb;7(1):14-31. Pubmed
  2. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed
  3. Piepho RW: Overview of the angiotensin-converting-enzyme inhibitors. Am J Health Syst Pharm. 2000 Oct 1;57 Suppl 1:S3-7. Pubmed
  4. Song JC, White CM: Clinical pharmacokinetics and selective pharmacodynamics of new angiotensin converting enzyme inhibitors: an update. Clin Pharmacokinet. 2002;41(3):207-24. Pubmed
Transporters

1. Multidrug resistance protein 1

Actions: inhibitor

Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells

UniProt ID: P08183 Link_out
Gene: ABCB1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

2. Oligopeptide transporter, small intestine isoform

Actions: substrate

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

UniProt ID: P46059 Link_out
Gene: SLC15A1 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Tsuji A: Transporter-mediated Drug Interactions. Drug Metab Pharmacokinet. 2002;17(4):253-74. Pubmed
Comments
Drug created on June 13, 2005 07:24 / Updated on February 08, 2013 16:19