Disease relevance of 56049-89-9

• Usual therapeutic doses of racemic indacrinone have only transient uricosuric activity, so that, as with other diuretics, hyperuricemia occurs [1].
• 6 MK-196 may offer a therapeutic advantage over HCT as an antihypertensive agent for use in the treatment of mild to moderate, essential hypertension [2].
• Under conditions of induced metabolic alkalosis, the urinary levels of MK-196 increased from 11 to 40% [3].
• 4 Both doses of MK-196 brought about significant decreases in body weight at Weeks 3 and 4 of drug treatment [2].

High impact information on 56049-89-9

• Although indacrinone and ticrynafen produced changes in cell shape in vitro, the beta-tubulin staining pattern of treated cells was not altered [4].
• Distinctive stereospecific effects on luminal tubular ion transport occur with indacrinone and etozoline [5].
• Effects of enantiomers of indacrinone (MK-196) on cation transport by the loop of Henle and distal tubule studied by microperfusion in vivo [6].
• Effects of MK-196 and furosemide on rat medullary thick ascending limbs of Henle in vitro [7].
• Bidirectional transport processes are operative in that MK-196 is secreted by the renal tubule and passively back diffuses across the tubular epithelium by a pH-dependent process [8].

Chemical compound and disease context of 56049-89-9

• A double-blind comparison of a novel indanone diuretic (MK-196) with hydrochlorothiazide in the treatment of essential hypertension [2].

Biological context of 56049-89-9

• Because of the marked natriuresis caused by MK-196, some increase in potassium excretion occurred [9].
• Clearances of MK-196 were not corrected for plasma protein binding of the drug which is very high (greater than 99%) [8].
• The biotransformation of (6,7-dichloro-2-methyl-1-oxo-2-phenyl-5-indanyloxy) acetic acid (MK-196) in the chimpanzee [3].
• MK-286 is a 90:10 mixture of the (+) and (-)-enantiomers of indacrinone, a combination which induces diuresis while maintaining isouricemia [10].
• Addition of tienilic acid and indacrinone at 1 mM to a suspension of freshly isolated cells caused dose-dependent loss of cell viability as judged by the LDH-latency test [11].

Anatomical context of 56049-89-9

• Expansion of the extracellular fluid volume and the infusion of MK-196 resulted in a higher fractional excretion of urate [12].
• Two new diuretic agents, piretanide and MK-196, inhibited short-circuit current (SCC) across the isolated frog corneal epithelium [13].
• These results suggest that piretanide and MK-196 selectively inhibit active Cl transport in the cornea by blocking Cl permeability of the apical side of the epithelial cells [13].

Associations of 56049-89-9 with other chemical compounds

• Clearance and micropuncture techniques were used to evaluate the effects of MK-196 on uric acid and electrolyte excretion by the rat kidney [14].
• Twenty-four hypertensive out-patients (WHO I) underwent an ambulatory 24-hour electrocardiogram-monitoring both before and after 8 weeks treatment with either hydrochlorothiazide (20-50 mg/day, N = 6), indacrinone (50-100 mg/day, N = 6) or indacrinone plus amiloride (50-100 mg and 5-10 mg/day, N = 12) in a double-blind fashion in 3 parallel groups [15].
• EP was measured before, during and for several hours after the intravenous injection of the following loop diuretics: furosemide, piretanide, bumetanide, ethacrynic acid, indacrinone stereoisomers and ozolinone [16].

Gene context of 56049-89-9

• (Laris, P.C., Pershadsingh, A., Johnstone, R.M., 1976, Biochim, Biophys. Acta 436:475-488) is shown to be valid only in the presence of the Cl- -channel blocker indacrinone (MK196) [17].

Analytical, diagnostic and therapeutic context of 56049-89-9

• Radioimmunoassays for the enantiomeric components of indacrinone and their phenolic metabolites [10].

References