**8. New aldosterone blockers**

Promising results with mineralocorticoid receptor antagonists in the treatment of hypertension and prevention of hypertension-related organ damage have prompted the search and possible development of new aldosterone antagonists. Search has followed two main strategies: the first has consisted in the development of non-steroidal antagonists that could overcome the side effects of spironolactone and canrenoate without losing the pharmacological properties of these compounds; the second has aimed at developing drugs that inhibit aldosterone biosynthesis and has resulted in the generation of aldosterone synthase direct inhibitors.

## **8.1 Non steroidal mineralocorticoid receptor antagonists**

The first strategy moved its initial steps from the demonstration that some dyhydropyridine calcium-channel blockers (CCBs) exerts also a mineralocorticoid receptor antagonist activity. Researchers in the Pfizer® laboratories reported that nimodipine, felodipine, and nitrendipine block aldosterone-induced receptor activation by competing with aldosterone binding to the receptor "ligand binding domain". The affinity of dihydropyridines for the receptor binding domain is lower than for the L-type calcium channels, indicating that inhibition of mineralocorticoid receptor activity is independent of the effects on calcium channels. The efficacy of dyihydropyridines as mineralocorticoid receptor antagonist is comparable to that of eplerenone, whereas non-dihydropyridine CCBs such as verapamil and diltiazem do not have any inhibitory activity.
