Discovery and development of ACE inhibitors

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ACE and inhibitor

Captopril structure

Enalapril structure

Lisinopril structure

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Keto-ACE

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A58365A

Discovery and development of ACE inhibitors

The discovery and development of ACE inhibitors (Angiotensin-Converting Enzyme inhibitors) represent a significant advancement in the field of cardiovascular medicine. ACE inhibitors are a class of medication primarily used for the treatment of hypertension (high blood pressure) and congestive heart failure.

History

The journey to the discovery of ACE inhibitors began with the study of the renin-angiotensin system (RAS), a hormone system that regulates blood pressure and fluid balance. In the 1950s, researchers identified the role of angiotensin II, a potent vasoconstrictor, in increasing blood pressure. The enzyme responsible for converting angiotensin I to angiotensin II was named angiotensin-converting enzyme (ACE).

In the 1960s, Brazilian scientist Sérgio Henrique Ferreira discovered a peptide in the venom of the Bothrops jararaca snake that inhibited the action of ACE. This peptide, known as bradykinin potentiating factor (BPF), laid the groundwork for the development of synthetic ACE inhibitors.

Development

The first synthetic ACE inhibitor, captopril, was developed in the late 1970s by researchers at Squibb Corporation (now part of Bristol-Myers Squibb). Captopril was approved by the Food and Drug Administration (FDA) in 1981 for the treatment of hypertension. Its success led to the development of other ACE inhibitors, including enalapril, lisinopril, and ramipril.

Mechanism of Action

ACE inhibitors work by inhibiting the activity of the angiotensin-converting enzyme, which decreases the production of angiotensin II. This results in the dilation of blood vessels, reduced blood pressure, and decreased workload on the heart. Additionally, ACE inhibitors increase the levels of bradykinin, a peptide that promotes vasodilation.

Clinical Uses

ACE inhibitors are used to treat a variety of cardiovascular conditions, including:

• Hypertension
• Congestive heart failure
• Chronic kidney disease
• Diabetic nephropathy
• Post-myocardial infarction

Side Effects

Common side effects of ACE inhibitors include:

• Cough
• Hyperkalemia (elevated potassium levels)
• Hypotension (low blood pressure)
• Angioedema (swelling of deeper layers of the skin)

Related Pages

• Renin-angiotensin system
• Hypertension
• Congestive heart failure
• Captopril
• Enalapril
• Lisinopril
• Ramipril