The Sound of Evolution
Sacubitril
Mechanism of action:
Sacubitril is a neprilysin inhibitor. Sacubitril is a prodrug and must be metabolized in the body into the active form sacubitrilat. Neprilysin is responsible for degrading multiple protective vasoactive peptides, including atrial natriuretic peptide and brain natriuretic peptide. When neprilysin is inhibited by sacubitrilat, the breakdown of vasoactive peptides is reduced, leading to vasodilation, natriuresis, diuresis, and suppression of myocardial fibrosis and ventricular remodeling.
Reference(s):
1. Gu J et al. (2010). Pharmacokinetics and pharmacodynamics of LCZ696, a novel dual-acting angiotensin receptor-neprilysin inhibitor (ARNi). J Clin Pharmacol.
2. Mills J et al. (2015). The Role of Neprilysin Inhibitors in Cardiovascular Disease. Curr Heart Fail Rep.
3. King JB et al. (2015). Neprilysin Inhibition in Heart Failure with Reduced Ejection Fraction: A Clinical Review. Pharmacotherapy.