ANTIMINERALOCORTICOIDS - PHARMACOLOGICAL PROSPECTS

The pharmacology of the mineralocorticoid receptor antagonist spironol actone and analogues is reviewed in the light of recent discoveries re garding the primary structure of corticosteroid receptors and the diff erent isoforms of the enzyme 11 beta-hydroxysteroid dehydrogenase. The type 2 isoform of this enzyme functions in some tissues to keep the a ldosterone receptor activation specific, i.e. it allows stimulation by aldosterone while eliminating glucocorticoids such as cortisol and co rticosterone. The type 2 isoform has been shown in the colon, hypothal amus, kidney, placenta and salivary gland. New clinical uses of aldost erone antagonists may be derived from these developments. Most promine nt in this respect appear to be myocardial fibrosis and specific forms of hypertension with altered mineralocorticoid receptor functioning a nd deficiencies in the protection system of the receptor against gluco corticoids.