The History of Captopril

Captopril is an oral drug and a member of a class of drugs called angiotensin converting enzyme (ACE) inhibitors. Captopril is used to treat high blood pressure and heart failure. It decreases certain chemicals that tighten the blood vessels, so blood flows more smoothly and the heart can pump blood more efficiently.
Captopril(CAS.NO:62571-86-2) 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. 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.

The development of captopril was amongst the earliest successes of the revolutionary concept of ligand-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 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 in 1967, when he found the conversion of angiotensin I to angiotensin II took place in the pulmonary circulation instead of in the plasma. In contrast, Sergio Ferreira found bradykinin disappeared in its passage through the pulmonary circulation. The conversion of angiotensin I to angiotensin II and the inactivation of bradykinin were thought to be mediated by the same enzyme.
In 1970, using bradykinin potentiating factor (BPF) provided by Sergio Ferreira, Ng and Vane found 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 venom of a lancehead viper (Bothrops jararaca), 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 became a generic medicine in the U.S. in February 1996, when the market exclusivity held by Bristol-Myers Squibb for captopril expired.
The development of captopril has been claimed as an instance of ‘biopiracy’ (commercialization of traditional medicines), since no benefits have flowed back to the indigenous Brazilian tribe who first used pit viper venom as an arrowhead poison.
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Captopril:application, dose, side effect,storage

Captopril is an angiotensin-converting enzyme (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.
1. What can Captopril be used for?
Captopril’s main uses are based on its vasodilation and inhibition of some renal function activities. These benefits are most clearly seen in the following conditions:

1) Hypertension

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

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.
2. How to store captopril
*Keep all medicines out of the reach and sight of children.

*Store in a cool, dry place, away from direct heat and light.
3. What happens if I miss a dose?
Take the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not take extra medicine to make up the missed dose.
4. What happens if I overdose?
Captopril (as other ACE inhibitors) overdose can be antagonized with naloxone.
5. What’s the side effects of Captopril?
Get emergency medical help if you have any of these signs of an allergic reaction to captopril: hives; severe stomach pain; difficulty breathing; swelling of your face, lips, tongue, or throat.
1)Call your doctor at once if you have:
*a light-headed feeling, like you might pass out;

*little or no urinating, or urinating more than usual;

*shortness of breath (even with mild exertion), swelling, rapid weight gain;

*chest pain or pressure, pounding heartbeats or fluttering in your chest;

*high potassium (slow heart rate, weak pulse, muscle weakness, tingly feeling); or

*sudden weakness or ill feeling, fever, chills, sore throat, painful mouth sores, pain when *swallowing, skin sores, cold or flu symptoms.
2)Common captopril side effects may include:
*cough;

*flushing (warmth, redness, or tingly feeling);

*numbness, tingling, or burning pain in your hands or feet;

*loss of taste sensation; or

*mild skin itching or rash.