Enalapril Maleate
(Vasotec)

The Discovery

The Mysterious Viper

In the jungles of Brazil, a deadly pit viper called Bothrops jararaca kills its prey in an unusua...

In the jungles of Brazil, a deadly pit viper called Bothrops jararaca kills its prey in an unusual way. When it bites, its venom doesn't just cause pain — it makes the victim's blood pressure drop so fast they pass out. In the 1960s, a young Brazilian pharmacologist named Sergio Ferreira became fascinated by this effect. He traveled to London to study the venom at the Royal College of Surgeons. He discovered that the venom contained small peptides that blocked an enzyme in the blood. This enzyme, called ACE, normally helps keep blood pressure stable. The snake's venom shut it down completely. Ferreira realized that if you could control this effect, you might cure high blood pressure.

The Breakthrough

The Deadly Discovery

Ferreira published his findings, and they caught the attention of scientists at the Squibb Instit...

Ferreira published his findings, and they caught the attention of scientists at the Squibb Institute in New Jersey. A biochemist named David Cushman and a chemist named Miguel Ondetti began working together to understand exactly how the snake venom peptides worked. They studied the three-dimensional shape of the ACE enzyme. They tested hundreds of snake venom fragments. By 1977, they had designed a completely new molecule that could block ACE — but unlike snake venom, it was safe for humans. They called it captopril. It was the first ACE inhibitor ever made. But captopril had problems: it tasted bad, caused rashes, and patients had to take it three times a day.

The Trials

The Connection

The Merck pharmaceutical company saw the potential and wanted to make something better.

The Merck pharmaceutical company saw the potential and wanted to make something better. Their scientists studied captopril's structure and realized they could redesign it. They needed a molecule that blocked ACE just as well but caused fewer side effects and lasted longer in the body. The team, led by chemist Arthur Patchett, spent years testing variations. They discovered that by adding a specific chemical group called an ethyl ester, they could create a prodrug — a molecule that was inactive when swallowed but became active once the liver processed it. This was the key insight that separated enalapril from captopril.

The Crisis

The Design

Enalapril was designed to be swallowed as a pill.

Enalapril was designed to be swallowed as a pill. Once it reached the liver, enzymes would strip off the ethyl ester group, converting it into its active form called enalaprilat. This was elegant chemistry. The prodrug approach meant the medicine entered the bloodstream slowly and steadily, so patients only needed to take it once or twice a day instead of three times. Clinical trials showed it worked just as well as captopril at lowering blood pressure but caused far fewer side effects. The rashes and taste problems were gone. Merck filed for FDA approval in 1985.

The Legacy

The Miracle Drug

The FDA approved enalapril under the brand name Vasotec in 1985.

The FDA approved enalapril under the brand name Vasotec in 1985. It became one of the best-selling drugs in history. Doctors prescribed it to millions of patients with high blood pressure and heart failure. Later studies showed that ACE inhibitors didn't just lower blood pressure — they actually protected the kidneys in diabetic patients and helped the heart heal after heart attacks. Today, enalapril is on the World Health Organization's List of Essential Medicines. It costs pennies per pill in generic form. The story that began with a deadly snake in Brazil ended with one of the safest, cheapest, and most widely used heart medicines on Earth. Over a billion people have taken ACE inhibitors since enalapril's approval.