Disease relevance of Canrenoate

• Spironolactone and potassium canrenoate are diuretics that are used widely for management of cirrhotic ascites [1].
• The administration of spironolactone frequently leads to feminization, which has been noted less frequently with the use of potassium canrenoate, a salt of the active metabolite of spironolactone [1].
• Membrane cholesterol increased 17% after 3 days of 30 mumoles canrenoate per 100 gm body weight per day; phospholipids decreased by 12% [2].
• In contrast, the fibrosis induced by isoprenaline was reduced significantly by potassium canrenoate at the three section levels [3].
• Effects of canrenoate on red cell sodium transport and calf flow in essential hypertension [4].

Psychiatry related information on Canrenoate

• Compared with placebo, canrenoate also distinctly reduced the time spent in slow-wave sleep (P < 0.005) [5].
• After canrenoate, ACTH and cortisol secretory responses during sleep and wakefulness did not differ and were comparable with those obtained in placebo-treated subjects during wakefulness [5].
• Canrenoate markedly diminished SWS (P less than 0.01) but left REM sleep unaffected [6].

High impact information on Canrenoate

• METHODS: Heart rate variability and baroreflex sensitivity were examined 30 min following the administration of potassium canrenoate (intravenous) (aldosterone antagonist) or saline (control) [7].
• Cortisol levels, however, were significantly higher after canrenoate, compared with placebo, whereas ACTH and hGH concentrations did not differ [8].
• Mineralocorticoid receptor blockade by canrenoate increases both spontaneous and stimulated adrenal function in humans [9].
• Canrenoate (200 mg, iv) or RU486 (400 mg, orally) was administered 150 min before a KCl load (1 mmol/kg BW, orally) in seven healthy males undergoing maximal water diuresis [10].
• However, canrenoate blunted the kaliuresis after the KCl load (51.9 +/- 4.4 mmol/5 h; P < 0.05 compared to KCl alone) and stimulated natriuresis in a complementary way [10].

Chemical compound and disease context of Canrenoate

• Membrane fluidity, as measured by the fluorescent probe 1,6-diphenyl-1,3,5-hexatriene decreased after treatment with 20 mumoles canrenoate per 100 gm body weight per day for 3 days [2].
• Equimolar sodium canrenoate, but not potassium chloride, had similar reversal effects on arrhythmias induced by long-term digoxin intoxication [11].
• We have re-evaluated 15 patients with idiopathic primary aldosteronism one month after withdrawal of therapy with aldosterone-receptor antagonist potassium canrenoate [12].
• Chronic experiments were carried out on three groups of rats to evaluate tissue and electrolyte effects of a mineralocorticoid blocker canrenoate potassium (SC-14266) during DOCA-induced hypokalemic metabolic alkalosis [13].
• We measured red blood cell Na+-K+ pump, Na+-Li+ countertransport and Na+-K+ cotransport activities, together with intraerythrocyte sodium content before and after 3 months therapy with captopril and two other antihypertensive drugs (atenolol and canrenoate potassium) in subjects suffering from essential hypertension [14].

Biological context of Canrenoate

• In the patients in whom exogenously administered ouabain was antagonized, canrenoate diminished blood pressure through vasodilation and heightened the red cell Na/K pump [4].
• Canrenoate disposition in dogs. Tissue distribution and elimination [15].
• Clinical study of potassium canrenoate on raised intracranial pressure [16].
• DNA damage in tissues of rat treated with potassium canrenoate [17].
• The acute effects of amiloride and potassium canrenoate on digoxin-induced positive inotropism in healthy volunteers [18].

Anatomical context of Canrenoate

• In-vivo metabolites of spironolactone and potassium canrenoate: determination of potential anti-androgenic activity by a mouse kidney cytosol receptor assay [19].
• Isoproterenol also induced cardiac fibrosis, which was completely inhibited in infarcted rats by potassium canrenoate alone in right and left ventricles [20].
• The difference in endocochlear and endolymphatic sac d.c. potentials in response to furosemide and canrenoate as diuretics [21].
• Ototoxic effect of potassium canrenoate on the guinea pig cochlea [22].
• Lymphocyte function tests in cirrhotic patients under treatment with spironolactone and potassium canrenoate [23].

Associations of Canrenoate with other chemical compounds

• To investigate if aldosterone-receptor blockade influences vasopressin type 2 receptor (V(2))-mediated renal water reabsorption and the renal expression of the vasopressin-regulated water channel aquaporin-2 (AQP2), rats were treated with the aldosterone-receptor antagonist canrenoate (20 mg/day iv) for 4 wk [24].
• Expression of osteopontin, cyclooxygenase-2, and ED-1 were elevated by DOCA treatment, blocked by potassium canrenoate, and (for ED-1 and osteopontin) partially reduced by cariporide [25].
• A new turbidometric digoxin immunoassay on the ADVIA 1650 analyzer is free from interference by spironolactone, potassium canrenoate, and their common metabolite canrenone [26].
• Mean blood pressure levels after captopril correlated positively with those after atenolol in the individual patients (P less than 0.0001); mean blood pressure levels after canrenoate potassium, on the contrary, did not correlate with those after the other two drugs [27].
• Intravenous infusion of glucose or amino acids increased these relationships, and after administration of UDCA or canrenoate, these relationships were still increased by at least 70% on average when compared with the control experiments [28].

Gene context of Canrenoate

• Pituitary-adrenocortical responsiveness during early sleep was disinhibited after canrenoate which is a selective blocker of mineralocorticoid receptors (MR) located primarily in limbic-hippocampal structures [29].
• In canrenoate-treated rats, the effect of OPC-31260 was significantly reduced, and semiquantiative immunoblotting demonstrated a significant reduction (45%) in AQP2 expression [24].
• On radioreceptor assay, plasma from mice chronically administered spironolactone contained approximately 10 times higher levels of androgen receptor active material than from mice administered potassium canrenoate [19].
• In canrenoate-treated rats, ANP infusion caused greater increases in sodium excretion (FENA from 3.05 +/- 0.71 to 7.21 +/- 0.45%; P < 0.05; n = 8) than saline infusion (FENA from 4.16 +/- 1.11 to 5.47 +/- 0.66%; n = 6), despite the hypocapnia [30].
• We conclude that long-term therapy with the aldosterone-receptor blocker, potassium canrenoate, can normalize the aldo/PRA ratio in many cases of idiopathic primary hyperaldosteronism after one-month withdrawal of the drug [12].

Analytical, diagnostic and therapeutic context of Canrenoate

• Identification of some human urinary metabolites of orally administered potassium canrenoate by stable isotope-labeling techniques [31].
• Canrenoate was rapidly converted to lipid- and water-soluble metabolites which were separated by thin-layer chromatography [15].
• Plasma levels and renal excretion of canrenone after oral administration of 200 mg of spironolactone and intravenous injection of 200 mg of potassium canrenoate to a healthy male volunteer were measured [32].
• The results provide information on the metabolism of oral potassium canrenoate in man, and demonstrate the utility of combining stable isotope labeling, lipophilic gel chromatography, and GC/MS in studies of steroidal spirolactones [31].
• 2. Wistar rats, challenged with either canrenoate or saline vehicle, were infused with 10 micrograms/kg per h ANP during acute hypocapnia achieved by mechanical ventilation [30].

References