Discovery and development of ACE inhibitors

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ACE and inhibitor

Discovery and Development of ACE Inhibitors

The discovery and development of Angiotensin-Converting Enzyme (ACE) inhibitors represent a significant milestone in the field of medicine and pharmacology, offering a revolutionary approach to treating hypertension (high blood pressure), heart failure, and certain types of kidney diseases. This article outlines the historical context, discovery, and subsequent development of ACE inhibitors, highlighting their impact on medical practice and patient care.

Historical Background

Before the advent of ACE inhibitors, treatment options for hypertension and heart failure were limited and often had undesirable side effects. The discovery of the renin-angiotensin system (RAS) in the 1950s laid the groundwork for understanding how blood pressure is regulated in the body, paving the way for targeted drug development.

Discovery

The discovery of ACE inhibitors can be traced back to the 1960s, with the pioneering work of Sergio Ferreira, who discovered a bradykinin potentiating factor (BPF) in the venom of the Brazilian pit viper, Bothrops jararaca. This finding led to the hypothesis that inhibition of the enzyme responsible for breaking down bradykinin, later identified as angiotensin-converting enzyme (ACE), could be a viable strategy for lowering blood pressure.

In the early 1970s, scientists at Squibb (now part of Bristol-Myers Squibb) led by David Cushman and Miguel Ondetti synthesized the first ACE inhibitor, captopril, based on the structure of BPF. Captopril was a breakthrough, demonstrating significant efficacy in lowering blood pressure with fewer side effects compared to existing treatments.

Development

Following the success of captopril, further research and development efforts led to the synthesis of more ACE inhibitors, including enalapril, lisinopril, and ramipril. These second-generation ACE inhibitors were designed to be longer-acting and were often prodrugs, requiring conversion in the body to their active form.

The development of ACE inhibitors involved extensive clinical trials to establish their efficacy, safety, and potential applications beyond hypertension. These trials have shown that ACE inhibitors not only lower blood pressure but also provide significant benefits in managing heart failure, protecting kidney function in patients with diabetes, and reducing the risk of stroke and heart attack.

Impact on Medical Practice

The introduction of ACE inhibitors has transformed the management of hypertension and heart failure, offering a more effective and better-tolerated treatment option. They are now a cornerstone in the treatment of these conditions, recommended by clinical guidelines worldwide.

Moreover, the success of ACE inhibitors has spurred further research into the renin-angiotensin system, leading to the development of angiotensin II receptor blockers (ARBs) and other therapies that target different aspects of the RAS.

Conclusion

The discovery and development of ACE inhibitors is a landmark event in the history of medicine, illustrating the power of translational research and the potential of nature as a source of therapeutic agents. Their impact on the treatment of cardiovascular diseases and beyond continues to be felt, improving the quality of life for millions of patients around the globe.

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