Lisinopril is a medication of the angiotensin-converting enzyme (ACE) inhibitor and is used to treat high blood pressure, heart failure, and after heart attacks. For high blood pressure it is usually a first-line treatment. It is also used to prevent kidney problems in people with diabetes mellitus. Lisinopril is taken by mouth. Full effect may take up to four weeks to occur.Common side effects include headache, dizziness, feeling tired, cough, nausea, and rash. Serious side effects may include low blood pressure, liver problems, high blood potassium, and angioedema. Use is not recommended during the entire duration of pregnancy as it may harm the baby. Lisinopril works by inhibiting the renin–angiotensin–aldosterone system.Lisinopril was patented in 1978 and approved for medical use in the United States in 1987. It is available as a generic medication. In 2020, it was the fourth most commonly prescribed medication in the United States, with more than 88 million prescriptions. In July 2016, an oral solution formulation of lisinopril was approved for use in the United States. Structure–activity relationships
Lisinopril has a proline group that is responsible for the availability of the drug in oral formulation. The carboxylate group interacts with zinc ions to inhibit the ACE enzyme found in the kidneys and lungs. The other substituents participate in binding the same enzyme. Unlike Captopril, another ACE Inhibitor, Lisinopril lacks a thiol group. Medical uses
Lisinopril is typically used for the treatment of high blood pressure, congestive heart failure, and diabetic nephropathy and after acute myocardial infarction (heart attack).
History
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). Enalapril is a derivative, designed by scientists at Merck to overcome the rash and bad taste caused by captopril. : 12–13 
Enalapril is actually a prodrug; the active metabolite is enalaprilat.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. 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.The discovery posed a problem, since sales of enalapril were strong for Merck, and the company did not want to diminish those sales.