Captopril
First oral ACE inhibitor derived from Brazilian pit viper venom, containing a thiol group for angiotensin-converting enzyme inhibition.
Chemical Identity
| Property | Value |
|---|---|
| Chemical Formula | C9H15NO3S |
| Molecular Weight | 217.3 Da |
| CAS Number | 62571-86-2 |
| Peptide Class | Tripeptide Derivative (ACE Inhibitor) |
| Route | Oral |
Structure
Captopril is a proline derivative containing a thiol (-SH) group that chelates the zinc ion in the ACE active site. Inspired by teprotide (a nonapeptide from Bothrops jararaca venom), it was designed as the first orally active ACE inhibitor with a minimal structure for zinc binding.
Mechanism of Action
Captopril’s thiol group binds the catalytic zinc ion of ACE, blocking conversion of angiotensin I to the vasoconstrictor angiotensin II. This reduces aldosterone secretion, decreases peripheral vascular resistance, and lowers blood pressure. Bradykinin degradation is also inhibited, contributing to vasodilation.
Clinical Applications
- Hypertension: First-line antihypertensive
- Heart failure: Improves survival (SAVE trial)
- Diabetic nephropathy: Renal protective effects
- Post-myocardial infarction: LV dysfunction (SAVE trial)
- Hypertensive crisis: Sublingual administration
Pharmacokinetics
- Half-life: 2 hours
- Tmax: 1 hour
- Bioavailability: 60-75%
- Metabolism: Hepatic (50%)
- Elimination: Renal (95%)
- Onset: 15-30 minutes
Safety and Side Effects
Cough (10-15%), hyperkalemia, renal impairment, angioedema (rare), dysgeusia (thiol-related), rash, and first-dose hypotension. Contraindicated in pregnancy and bilateral renal artery stenosis.
References
- Cushman, D.W., & Ondetti, M.A. (1991). History of captopril design. Nature Medicine, 3, 746-748.
- Pfeffer, M.A., et al. (1992). SAVE trial: captopril after myocardial infarction. New England Journal of Medicine, 327, 669-677.
Test Your Knowledge
Reinforce what you learned about Captopril with interactive quizzes on Wikipept.
Take a Quiz on Wikipept