Mechanism of Action of Finerenone
Finerenone is a nonsteroidal mineralocorticoid receptor antagonist (MRA) that selectively blocks sodium reabsorption through the mineralocorticoid receptor and reduces overactivation of this receptor in the kidney, heart, and blood vessels. 1
Molecular Mechanism
Finerenone binds to a helix domain in the mineralocorticoid receptor, providing potent and selective blockade that inhibits receptor function. 2
Unlike steroidal MRAs (spironolactone, eplerenone), finerenone's nonsteroidal structure allows for more selective MR binding with reduced off-target hormonal effects. 3, 4
The selective binding prevents upregulation of genes that encode facilitators of tissue damage, inflammation, and fibrosis. 2
Pathophysiological Effects
Finerenone blocks overactivation of the mineralocorticoid receptor in three key organ systems: kidneys, heart, and blood vessels. 1
By antagonizing the MR, finerenone reduces oxidative stress, inflammation, and fibrosis in cardiac and renal tissue. 2
The drug targets inflammatory and fibrotic pathways that drive disease progression and organ damage in patients with chronic kidney disease and type 2 diabetes. 4
Sodium and Potassium Handling
Finerenone blocks sodium reabsorption through the mineralocorticoid receptor, which is the primary mechanism for its blood pressure-lowering effects. 1
The sodium-blocking action occurs without the same degree of potassium retention seen with steroidal MRAs, though hyperkalemia remains a monitored adverse effect (14% vs 6.9% with placebo). 1
Comparative Pharmacology
Finerenone demonstrates superior selectivity for the mineralocorticoid receptor compared to spironolactone, which has significant off-target effects on androgen and progesterone receptors causing gynecomastia and hirsutism. 5, 4
The nonsteroidal structure provides equipotent MR antagonism to spironolactone but with a more favorable safety profile regarding hormonal side effects. 3, 5
Compared to eplerenone (second-generation steroidal MRA), finerenone shows improved selectivity and reduced impact on renal function while maintaining potent MR blockade. 5