Capoten ®

Bristol-Myers Squibb

Captopril (rINN) (pronounced /ˈkæptəprɪl/) is an angiotensin-converting enzyme inhibitor (ACE inhibitor) used for the treatment of hypertension and some types of congestive heart failure. Captopril was the first ACE inhibitor developed and was considered a breakthrough both because of its novel mechanism of action and also because of the revolutionary development process. Captopril is commonly marketed by Bristol-Myers Squibb under the trade name Capoten.

Clinical use

Captopril’s main uses are based on its vasodilatation and inhibition of some renal function activities. These benefits are most clearly seen in the following conditions:

1) Hypertension

2) Cardiac conditions such as post myocardial infarction and congestive heart failure

3) Preservation of kidney function in diabetic nephropathy

Additionally, it has shown mood-elevating properties in some patients. This is consistent with the observation that animal screening models indicate putative antidepressant activity for this compound, although there has been one negative study. Formal clinical trials in depressed patients have not been reported.[1]

It has also been investigated for use in the treatment of cancer.[2

Effectiveness for hypertension

A 2004 study compared the effectiveness of captopril to a standardized extract of Hibiscus sabdariffa, a plant used to make Hibiscus tea and known to be effective at treating hypertension. The study found that both treatments were effective, and did not find any significant differences between the two treatments in terms of hypotensive effect, antihypertensive effectiveness, or tolerability.[3]


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 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-aldosteronerenin and ACE. Captopril was the culmination of efforts by Squibb’s laboratories to develop an ACE inhibitor. 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

Ondetti, Cushman and colleagues built on work that had been done in the 1960s by a team of researchers led by John Vane at the Royal College of Surgeons of England. The first breakthrough was made by Kevin K.F.Ng [4][5][6] in 1967 when he found that the conversion of angiotensin I to angiotensin II took place in the pulmonary circulation instead of in the plasma. In contrast, Sergio Ferreira[7][8] found that bradykinin disappeared in its passage through the pulmonary circulation. The conversion of angiotensin I to angiotensin II and the inactivation of bradykinin was thought to be mediated by the same enzyme.

In 1970, using bradykinin potentiating factor (BPF) provided by Sergio Ferreira,[9] Ng and Vane found that the conversion of angiotensin I to angiotensin II was inhibited during its passage through the pulmonary circulation. BPF was later found to be a peptide in the pit viper (Bothrops jararaca) venom which was a “collected-product inhibitor” of the converting enzyme. 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.

Captopril gained FDA approval on April 6, 1981. The drug went generic in the U.S. in February 1996 as a result of the end of market exclusivity for Bristol-Myers Squibb.

Developments from captopril

Limitations of captopril

The adverse drug reaction (ADR) profile of captopril is similar to other ACE inhibitors, with cough being the most common ADR.[10] However, captopril is also commonly associated with rash and taste disturbances (metallic or loss of taste), which are attributed to the unique sulfhydryl moiety.[11]

Captopril also has a relatively poor pharmacokinetic profile. The short half-life necessitates 2–3 times daily dosing, which may reduce patient compliance.

Subsequent ACE inhibitors

The adverse effect and pharmacokinetic limitations of captopril stimulated the development enalapril and subsequent ACE inhibitors. These were specifically designed to lack the sulfhydryl moiety believed to be responsible for rash and taste disturbance.[12] Most subsequent ACE inhibitors are given as prodrugs, to improve oral bioavailability. All have a longer half-life and are given once or twice daily, which may improve patient compliance.

Adverse effects

Adverse effects of captopril include cough, angioedema, agranulocytosis, proteinuria, hyperkalemia, taste alteration, teratogenicity, postural hypotension, acute renal failure and leukopenia. [13]. Except for postural hypotension which occurs due to short and fast mode of action of captopril, most of the side effects mentioned are common for all ACE inhibitors. Among these cough is the most common adverse effect and is due to elevated levels of bradykinin. Hyperkalemia can occur especially if used along with other drugs which elevate potassium level in blood like potassium sparing diuretics.

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