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Structural formula of lisinopril
Ball-and-stick model of the lisinopril zwitterion
Chemical structure of lisinopril
Clinical data
Pronunciation/lˈsɪnəprɪl/, ly-SIN-ə-pril
Trade namesPrinivil,[1] Zestril,[2] Qbrelis,[3] Dapril,[4] others[5]
Other names(2S)-1-[(2S)-6-amino-2-{[(1S)-1-carboxy-3-phenylpropyl]amino}hexanoyl]pyrrolidine-2-carboxylic acid
License data
Routes of
ATC code
Legal status
Legal status
Pharmacokinetic data
Bioavailabilityapprox. 25%, but wide range between individuals (6 to 60%)
Protein binding0
Elimination half-life12 hours
ExcretionEliminated unchanged in urine
  • (2S)-1-[(2S)-6-amino-2-[[(1S)-1-carboxy-3-phenylpropyl]amino]hexanoyl]pyrrolidine-2-carboxylic acid
CAS Number
PubChem CID
PDB ligand
CompTox Dashboard (EPA)
ECHA InfoCard100.071.332 Edit this at Wikidata
Chemical and physical data
Molar mass405.495 g·mol−1
3D model (JSmol)
  • 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 checkY
 ☒NcheckY (what is this?)  (verify)

Lisinopril is a medication belonging to the drug class of angiotensin-converting enzyme (ACE) inhibitors and is used to treat hypertension (high blood pressure), heart failure, and heart attacks.[7] For high blood pressure it is usually a first-line treatment. It is also used to prevent kidney problems in people with diabetes mellitus.[7] Lisinopril is taken orally (swallowed by mouth).[7] Full effect may take up to four weeks to occur.[7]

Common side effects include headache, dizziness, feeling tired, cough, nausea, and rash.[7] Serious side effects may include low blood pressure, liver problems, hyperkalemia (high blood potassium), and angioedema.[7] Use is not recommended during the entire duration of pregnancy as it may harm the baby.[7] Lisinopril works by inhibiting the renin–angiotensin–aldosterone system.[7]

Lisinopril was patented in 1978 and approved for medical use in the United States in 1987.[7][11] It is available as a generic medication.[7] In 2021, it was the fourth most commonly prescribed medication in the United States, with more than 88 million prescriptions.[12][13] In July 2016, an oral solution formulation of lisinopril was approved for use in the United States.[7][14]

Medical uses[edit]

Lisinopril is typically used for the treatment of high blood pressure, congestive heart failure, and diabetic nephropathy and after acute myocardial infarction (heart attack).[7][1] Lisinopril is part of the ACE inhibitors drug class.[1] Lisinopril is indicated for the treatment of hypertension, adjunctive therapy for heart failure, and acute myocardial infarction.[1]


Lisinopril is contraindicated in people who have a history of angioedema (hereditary or idiopathic) or who have diabetes and are taking aliskiren.[1]

Adverse effects[edit]

Common side effects include headache, dizziness, feeling tired, cough, nausea, and rash.[7] Serious side effects may include low blood pressure, liver problems, hyperkalemia, and angioedema.[7] Use is not recommended during the entire duration of pregnancy as it may harm the baby.[7]

Pregnancy and breastfeeding[edit]

Animal and human data have revealed evidence of harm to the embryo and teratogenicity associated with ACE inhibitors.[1]


Dental care[edit]

ACE-inhibitors like lisinopril are considered to be generally safe for people undergoing routine dental care, though the use of lisinopril prior to dental surgery is more controversial, with some dentists recommending discontinuation the morning of the procedure.[15] People may present to dental care suspicious of an infected tooth, but the swelling around the mouth may be due to lisinopril-induced angioedema, prompting emergency and medical referral.[15]


Lisinopril is the lysine-analog of enalapril. Unlike other ACE inhibitors, it is not a prodrug, is not metabolized by the liver, and is excreted unchanged in the urine.[1]

Mechanism of action[edit]

Lisinopril is an ACE inhibitor, meaning it blocks the actions of angiotensin-converting enzyme (ACE) in the renin–angiotensin–aldosterone system (RAAS), preventing angiotensin I from being converted to angiotensin II. Angiotensin II is a potent direct vasoconstrictor and a stimulator of aldosterone release. Reduction in the amount of angiotensin II results in relaxation of the arterioles. Reduction in the amount of angiotensin II also reduces the release of aldosterone from the adrenal cortex, which allows the kidney to excrete sodium along with water into the urine, and increases retention of potassium ions.[16] Specifically, this process occurs in the peritubular capillaries of the kidneys in response to a change in Starling forces.[17] The inhibition of the RAAS system causes an overall decrease in blood pressure.[16]



Following oral administration of lisinopril, peak serum concentrations of lisinopril occur within about seven hours,[1][16] although there was a trend to a small delay in time taken to reach peak serum concentrations in acute myocardial infarction patients. The peak effect of lisinopril is about 6 hours after administration for most people.[18][19] Declining serum concentrations exhibit a prolonged terminal phase, which does not contribute to drug accumulation. This terminal phase probably represents saturable binding to ACE and is not proportional to dose. Lisinopril does not undergo metabolism and absorbed drug is excreted unchanged entirely in the urine. Based on urinary recovery, the mean extent of absorption of lisinopril is approximately 25% (reduced to 16% in people with New York Heart Association Functional Classification (NYHA) Class II–IV heart failure), with large interpatient variability (6 to 60%) at all doses tested (5 to 80 mg).[1][16] Lisinopril absorption is not affected by the presence of food in the gastrointestinal tract.[18][20][21]

Studies in rats indicate that lisinopril crosses the blood-brain barrier poorly. Multiple doses of lisinopril in rats result in little or no accumulation in brain tissue.[22]


Lisinopril does not bind to proteins in the blood.[1][16] It does not distribute as well in people with NYHA Class II–IV heart failure.[1][16]


Lisinopril leaves the body completely unchanged in the urine.[1][16] The half-life of lisinopril is 12 hours, and is increased in people with kidney problems.[1][16] While the plasma half-life of lisinopril has been estimated between 12 and 13 hours, the elimination half-life is much longer, at around 30 hours.[18] The full duration of action is between 24 and 30 hours.[18]

Lisinopril is the only water-soluble member of the ACE inhibitor class, and thus has no metabolism by the liver.[18]


Pure lisinopril powder is white to off white in color.[1] Lisinopril is soluble in water (approximately 13 mg/L at room temperature),[23] less soluble in methanol, and virtually insoluble in ethanol.[1]


Captopril, the first ACE inhibitor, is a functional and structural analog of a peptide derived from the venom of the jararaca, a Brazilian pit viper (Bothrops jararaca).[24] Enalapril is a derivative, designed by scientists at Merck to overcome the rash and bad taste caused by captopril.[25][26]: 12–13  Enalapril is actually a prodrug; the active metabolite is enalaprilat.[27]

The di-acid metabolite of enalapril, enalaprilat, and its lysine analogue lisinopril are potent inhibitors of angiotensin converting enzyme (ACE); they do not contain sulphydryl groups. Both drugs can be assayed by high pressure liquid chromatography and by radioimmunoassay and plasma ACE inhibition remains stable under normal storage conditions. It is therefore possible to study their pharmacokinetics as well as their pharmacodynamic effects in humans. Enalaprilat and lisinopril as well as ACE activity have been measured in blood taken during the course of two studies of the effects of these drugs on blood pressure and autonomic responsiveness.

Lisinopril is a synthetic peptide derivative of captopril.[23] Scientists at Merck created lisinopril by systematically altering each structural unit of enalaprilat, substituting various amino acids. Adding lysine at one end of the drug turned out to have strong activity and had adequate bioavailability when given orally; analogs of that compound resulted in lisinopril, which takes its name from the discovery with lysine. Merck conducted clinical trials, and the drug was approved for hypertension in 1987 and congestive heart failure in 1993.[27]

The discovery posed a problem, since sales of enalapril were strong for Merck, and the company did not want to diminish those sales. Merck ended up entering into an agreement with Zeneca under which Zeneca received the right to co-market lisinopril, and Merck received the exclusive rights to an earlier stage aldose reductase inhibitor drug candidate, a potential treatment for diabetes. Zeneca's marketing and brand name, "Zestril", turned out to be stronger than Merck's effort.[28] The drug became a blockbuster for AstraZeneca (formed in 1998), with annual sales in 1999 of $1.2B.[29]

The US patents expired in 2002.[29] Since then, lisinopril has been available under many brand names worldwide; it is also available in combination drugs with diuretic hydrochlorothiazide (as lisinopril/hydrochlorothiazide), and with calcium channel blocker amlodipine (as lisinopril/amlodipine).[5]


  1. ^ a b c d e f g h i j k l m n o p "Prinivil- lisinopril tablet". DailyMed. 4 November 2019. Retrieved 27 February 2020.
  2. ^ a b "Zestril- lisinopril tablet". DailyMed. 31 October 2019. Retrieved 5 August 2020.
  3. ^ a b "Qbrelis- lisinopril solution". DailyMed. 31 March 2020. Retrieved 5 August 2020.
  4. ^ "Dapril". Drugs.com. Drugsite Trust. Retrieved 13 August 2021.
  5. ^ a b "Lisinopril". Drugs.com. Retrieved 23 December 2018.
  6. ^ a b "Lisinopril Use During Pregnancy". Drugs.com. 22 October 2019. Retrieved 27 February 2020.
  7. ^ a b c d e f g h i j k l m n o p "Lisinopril Monograph for Professionals". Drugs.com. American Society of Health-System Pharmacists. Retrieved 23 December 2018.
  8. ^ "FDA-sourced list of all drugs with black box warnings (Use Download Full Results and View Query links.)". nctr-crs.fda.gov. FDA. Retrieved 22 October 2023.
  9. ^ "Product monograph brand safety updates". Health Canada. February 2024. Retrieved 24 March 2024.
  10. ^ "Summary of Product Characteristics (SmPC) – (emc)". Lisinopril 10mg Tablet. 13 November 2019. Archived from the original on 28 February 2020. Retrieved 27 February 2020.
  11. ^ Fischer J, Ganellin CR (2006). Analogue-based Drug Discovery. John Wiley & Sons. p. 467. ISBN 978-3-527-60749-5.
  12. ^ "The Top 300 of 2021". ClinCalc. Archived from the original on 15 January 2024. Retrieved 14 January 2024.
  13. ^ "Lisinopril – Drug Usage Statistics". ClinCalc. Retrieved 14 January 2024.
  14. ^ "Drug Approval Package: Qbrelis (lisinopril)". U.S. Food and Drug Administration (FDA). 29 July 2016. Retrieved 5 August 2020.
  15. ^ a b Weinstock RJ, Johnson MP (April 2016). "Review of Top 10 Prescribed Drugs and Their Interaction with Dental Treatment". Dental Clinics of North America. 60 (2): 421–434. doi:10.1016/j.cden.2015.11.005. PMID 27040293.
  16. ^ a b c d e f g h Katzung B (2012). Basic and Clinical Pharmacology. New York: McGraw Hill. pp. 175, 184–185. ISBN 978-0-07-176401-8.
  17. ^ Reddi A (2018). "Disorders of ECF Volume: Nephrotic Syndrome". Fluid, Electrolyte and Acid-Base Disorders. Springer. ISBN 978-3-319-60167-0.
  18. ^ a b c d e Khan MG (2015). "Angiotensin-Converting Enzyme Inhibitors and Angiotensin II Receptor Blockers". Cardiac Drug Therapy. New York: Springer. ISBN 978-1-61779-962-4.
  19. ^ "Lisinopril". Wolters Kluwer Clinical Drug Information. Wolters Kluwer. 2024.
  20. ^ "Lisinopril Tablets, USP". dailymed.nlm.nih.gov. Retrieved 16 October 2022.
  21. ^ "Lisinopril: Package Insert / Prescribing Information". Drugs.com. Retrieved 16 October 2022.
  22. ^ Tan J, Wang JM, Leenen FH (February 2005). "Inhibition of brain angiotensin-converting enzyme by peripheral administration of trandolapril versus lisinopril in Wistar rats". American Journal of Hypertension. 18 (2 Pt 1): 158–164. doi:10.1016/j.amjhyper.2004.09.004. PMID 15752941.
  23. ^ a b "Lisinopril". PubChem. Retrieved 6 June 2018.
  24. ^ Patlak M (March 2004). "From viper's venom to drug design: treating hypertension". FASEB J. 18 (3): 421. doi:10.1096/fj.03-1398bkt. PMID 15003987. S2CID 1045315.
  25. ^ Jenny Bryan for The Pharmaceutical Journal, 17 April 2009 "From snake venom to ACE inhibitor – the discovery and rise of captopril"
  26. ^ Li JJ (2013). "History of Drug Discovery". In Li JJ, Corey EJ (eds.). Drug Discovery: Practices, Processes, and Perspectives. John Wiley & Sons. ISBN 978-1-118-35446-9.
  27. ^ a b >Menard J, Patchett AA (2001). Richards FM, Eisenberg DS, and Kim PS (eds.). "Angiotensin-converting enzyme inhibitors". Advances in Protein Chemistry. 56. Academic Press: 13–75. doi:10.1016/s0065-3233(01)56002-7. ISBN 978-0-08-049338-1. PMID 11329852.
  28. ^ Glover DR (2016). "Merck Sharp and Dohme: lisinopril section". Vie D'or: Memoirs of a Pharmaceutical Physician. Troubador Publishing Ltd. ISBN 978-1-78589-494-7.
  29. ^ a b Express Scripts. Patent expirations

Further reading[edit]