Agonists mineralocorticoid

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. 

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. 

Patients with orthostatic hypotension may require mineralocorticoids or adrenergic agonists. 

Metalol, 41 Metformin, 20 Methacycline, 227 Methadone, 328 Methionine enkephalin, 317 Methisazone, 350 Methixene, 413 17-Methyltestosterone, 156 Methgnodlol diacetate, 149 Methysergide, 477 Metiamide, 252 Metiapine, 429 Metizoline, 256 Metolazone, 384 Metoprolol, 109 Mexenone, 175 Mianserin, 451 Mibolerone, 144 Miconazole, 249 Midaflur, 259 Migraine, 477 Milipertine, 341 Mimbane, 347 Mineralocorticoids, 177 Minocycline, 228 Mixed agonists-antagonists, 318... 

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. 

Fig. 5. Specificity of steroid response element. A. In this example (mouse mammary tumour virus), the element will bind receptors for glucocorticoids (G), androgen (A), progestin (P) and mineralocorticoid (M) so that each of these classes of steroid stimulate transcription. This type of specificity can vary from cell to cell possibly due to other protein factors (not shown). B. Although oestrogen (E) receptor will not act as an agonist for mouse mammary tumour virus transcription, it may antagonise the agonist activity of glucocorticoids (G).

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>. 

Massaad C, Lombes M, Aggerbeck M, Rafestin-Oblin ME, Barouki R. Cell-specific, promoter-dependent mineralocorticoid agonist activity of spironolactone. Mol. Pharmacol. 1997 51 285-292. 

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

---