The story of modern hypertension treatment began not in a pharmaceutical laboratory, but in the Brazilian rainforest with a deadly pit viper. In the 1960s, Brazilian pharmacologist Sérgio Henrique Ferreira was studying the venom of Bothrops jararaca, a snake whose bite causes victims’ blood pressure to plummet catastrophically. Ferreira identified a peptide fraction he called “bradykinin-potentiating factor” (BPF) that enhanced the blood-pressure-lowering effects of bradykinin. When he brought this venom extract to Nobel laureate John Vane’s laboratory in London, the team discovered that BPF selectively inhibited angiotensin-converting enzyme (ACE), the key regulator of blood pressure.
This discovery launched a rational drug design program at what is now Bristol Myers Squibb. Researchers initially developed teprotide, a nonapeptide identical to the venom component, but it lacked oral bioavailability. Through systematic modification guided by structure-activity relationships, they identified that the terminal sulfhydryl group was critical for potency. After 60 compounds and 18 months of optimization, captopril emerged as the first orally active ACE inhibitor in 1977.
Captopril’s mechanism elegantly mirrors the viper’s natural strategy. By blocking ACE, it simultaneously prevents conversion of angiotensin I to the potent vasoconstrictor angiotensin II and preserves the vasodilator bradykinin. This dual action reduces systemic vascular resistance, decreases cardiac workload, and improves blood flow.
Approved by the FDA in 1981, captopril revolutionized cardiovascular medicine. It became the cornerstone for hypertension, heart failure, and post-myocardial infarction care, spawning an entire drug class that now includes lisinopril, enalapril, and ramipril. Over four decades, ACE inhibitors have prevented millions of strokes, heart attacks, and deaths worldwide.
Recent research continues to reveal captopril’s protective effects beyond blood pressure control. A 2025 review demonstrated its ability to prevent post-infarction ventricular remodeling, reduce infarct size, and improve coronary blood flow in animal models. The drug’s legacy exemplifies how lethal venom, when understood at the molecular level, can be transformed into life-saving therapy.
– Rashmi Kumari
