Captopril Essay

History of Captopril

In the mid of 1950s, angiotensin converting enzyme (ACE) was identified as the enzyme which converts angiotensin I to angiotensin II (vasoconstrictor substance). The cause of hypertension was actively investigated by John R. Vane in the 1960s. In 1967, Kevin K.F. Ng found the angiotensin I converts to angiotensin II in pulmonary circulation. During this time, Sergio Ferreira joined Vane’s team. Differ from Ng, Ferreira found bradykinin missing in its passage through the pulmonary circulation. Conversion of angiotensin I to angiotensin II and bradykinin inactivation were thought to be caused by the same enzyme. Ferreira brought bradykinin potentiating factor (BPF) extract of the venom of a lance head viper Bothrops jararaca.

Captopril was developed from this peptide after discovered via QSAR-based modification that the peptide’s terminal sulfhydryl moiety gave a high potency of ACE inhibition. Vane’s laboratory observations showed peptides are not absorbed when taken orally but it is effective when injected in the animal body. Vane arranged the first clinical test performed in the United Kingdom since United States Food and Drug Administration (FDA) refused the application of Squibb to conduct this experiment because angiotensin I was not marketed in the country. But in later, FDA allowed Squibb to continue the experiment in the United States in essential hypertension patients when the predicted ACE inhibition was demonstrated in human beings in United Kingdom. Dr Laragh performed the initial clinical trial in United States. Smith, the V.P. for R&D at Squibb recalled 17 essential hypertension patients were treated and the blood pressure came down in 14. Through this finding, company scientists accomplished to develop an orally active drug. FDA approved use of Captopril on 6th April 1981. In February 1996, Captopril became a generic medicine in the United States when the market only held by Bristol-Myers Squibb expired. Now, Captopril is commonly prescribed for