Captopril was developed in 1975 by three researchers at the U.S. drug company Squibb (now Bristol-Myers Squibb): Miguel Ondetti, Bernard Rubin and David Cushman. Squibb filed for U.S. patent protection on the drug in February 1976 and U.S. Patent 4,046,889 was subsequently granted in September 1977.

The development of captopril was amongst the earliest successes of the revolutionary concept of structure-based drug design. The renin-angiontensin-aldosterone system had been extensively studied in the mid-20th century and it had been decided that this system presented several opportune targets in the development of novel treatments for hypertension. The first two targets that were attempted were renin and ACE. Captopril was the culmination of efforts by Squibb's laboratories to develop an ACE inhibitor.

Ondetti, Cushman and colleagues built on work that had been done in the 1960s by the British pharmacologist John Vane when he was a researcher at the Royal College of Surgeons. Working with a Brazilian colleague, Sérgio Ferreira, Vane discovered a peptide in pit viper (Bothrops jararaca) venom which was a 'collected-product inhibitor' of angiotensin II. Captopril was developed from this peptide after it was found via QSAR-based modification that the terminal sulfhydryl moiety of the peptide provided a high potency of ACE inhibition.

Capoten® gained FDA approval in June 1981. Following this, the drug went generic in the U.S. in February 1996 as a result of the end of market exclusivity for Bristol-Myers Squibb.

Please visit the official site of the FDA for further information.

 

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