Aldosterone agonists

Spironolactone is the most clinically usehil steroidal aldosterone antagonist, and unlike GR antagonists, this compound is utilized much more frequendy than aldosterone agonists. Interfering with reabsorption and secretion in the late distal segment, this compound is predominantiy used with other diuretics. Canrenone, an olefinic metaboHte of spironolactone, and potassium canrenoate, in which the C-17 lactone has been hydrolyzed open, are also potent mineralocorticoid antagonists. 

Drugs with mineralocorticoidlike activity (aldosterone agonists) are frequently administered as replacement therapy whenever the natural production of mineralo-corticoids is impaired. Mineralocorticoid replacement is usually required in patients with chronic adrenocortical insufficiency (Addison disease), following adrenalectomy, and in other forms of adrenal cortex hypofunction. These conditions usually require both mineralocorticoid and glucocorticoid replacement. 

We will consider two drugs that exhibit this phenomenon. Spironolactone (I), which is a diuretic steroidal aldosterone agonist, crystallises as two polymorphic forms and also as four solvated crystalline forms depending on the solvents and methods used for crystallisation. We will consider the occurrence of solvated forms in section 1.4 at the moment we will concentrate on the two polymorphs only. Form 1 is produced when spironolactone powder is dissolved in acetone at a temperature very close to the boiling point and the solution is then cooled within a few hours down to O C. Form 2 is produced when the powder is dissolved in acetone, dioxane or chloroform at room temperature and the solvent is allowed to spontaneously evaporate over a period of several weeks. In both polymorphs the steroid nuclei (A, B, C and D rings)... 

Nuclear receptors, steroid hormone receptors Mineralocorticoid receptor Aldosterone (agonist)... 

Spironolactone (17-hydroxy-7 a-mercapto-3-oxo-17 a-pregn-4-ene-21-carboxylic acid), a diuretic steroidal aldosterone agonist, has been obtained into anhydrous polymorphs as well as four solvated crystalline forms [38]. The compound shows variable and incomplete oral absorption due to its poor water solubility and dissolution rate, factors that are compounded by the existence of polymorphism and solvate formation. The two anhydrate forms (Forms I and II) both crystallize in orthorhombic space groups, and the crystallographic data for these are collected in Table 15. The spironolactone system exhibits the classic... 

The client is diagnosed with primary hyperaldosteronism and prescribed the aldosterone agonist spironolactone (Aldactone). Which data would support that the medication is effective ... 

The main mineralocorticoid agonist in humans is aldosterone. Additionally, cortisol, corticosterone, and DOC have also mineralocorticoid agonistic activity. The synthetic steroid fludrocortisone (9a-fluorocorti-sol) is extremely potent and usually chosen for replacement mineralocorticoid therapy. In contrast, aldosterone and DOC are not useful in oral therapy due to rapid degradation in liver after absorption. 

Adrenergic blocking agents, 241 Adrenergic nervous system, 62 Adrenosterone, 176 Agonists, 20 Aldosterone, 206 Allergen, 41... 

Cortisol, corticosterone, aldosterone, and the synthetic steroids used in steroid therapy (e.g., prednisolone, dexamethasone, and triamcinolone) are glucocorticoid agonists and therefore elicit glucocorticoid responses. A number of other steroids bind to the glucocorticoid receptor and thus suppress glucocorticoid responses. 

Lefebvre H, Cartier D, Duparc C, et al. Effect of serotonin4 (5-HT4) receptor agonists on aldosterone secretion in idiopathic hyperaldosteronism. Endocr Res 2000 26 583-587. 

Lefebvre H, Gonzalez KN, Contesse V, Delarue C, Vaudry H, Kuhnl JM. Effect of prolonged administration of the serotonin4 (5-HT4) receptor agonist cisapride on aldosterone secretion in healthy volunteers. Endocr Res 1998 24 749-752. 

This shift in the substrate specificity of phospholipase C may persist for some time after the removal of agonist and may contribute to the phenomenon of cellular memory in the adrenal. When glomerulosa cells are sequentially exposed to All (20 minutes)-, no agonist (10 minutes), and again All, the character of the response elicited by the second addition of All differs dramatically from that elicited by the first the cell seems to remember its prior exposure to All [29], Although this second addition of All induces a smaller calcium transient, the rate of aldosterone secretion increases more rapidly and reaches a higher plateau value than is seen in response to the first exposure to the hormone. This result suggests either that the second addition of All elicits a smaller increase in 1,4,5-IP3 as a result of an altered... 

The mineralocorticoid aldosterone is also produced by the adrenal cortex and promotes retention of H20 and Na+ and loss of K+ by the kidney. Cortisol is also an agonist of the aldosterone receptor but the level of cortisol is kept low by type 2 11 (Thydroxysteroid dehydrogenase, which converts cortisol to the inactive cortisone (11-dehydrocortisol). Accordingly inhibition of this enzyme by 18(i>-glycyrrhetinic acid (from liquorice) elevates cortisol with consequent effects of H20 and Na+ retention, oedema and hypertension. Further potential sites of interference by plant substances with steroid hormone metabolism include enzymes involved in steroid hormone synthesis such as the cytochrome P450-linked 11 -hydroxylase that catalyses the last step of corticosterone synthesis. 

Spiro compounds 202 and 203 are antagonists of the mineralocorticoid receptor. This limits the production of excess aldosterone, which, in turn, leads to increased sodium uptake and potassium loss. This condition, known as Conn s syndrome, is associated with hypertension <2005W02005110992>. Amine 204 is a seratonergic 5-HY5-HT2 agonist for the treatment of glaucoma <2003W003051352>. 

Fischer AK, von Rosenstiel P, Fuchs E, Goula D, Almeida OF, Czeh B (2002) Tire prototypic miiierulcorticoid rec tor agonist aldosterone influences neur ogenesis in tire dentate gyms of tire adr enalectomized rat. Brain Res 947 290—293. 

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