Pharmacology of enantiomers and (-) p-OH metabolite of indacrinone.
Indacrinone, a racemic mixture, is a loop-blocking diuretic with effects on uric acid elimination that differ from those of furosemide. A series of studies in healthy men was undertaken to characterize the pharmacologic activity of the positive (+) and negative (-) enantiomers (E) of indacrinone and its (-) p-OH metabolite, (-) MET. All subjects were on sodium- and potassium-controlled diet; each experiment was similar in design and included placebo and positive controls. Oral (-)E and (-)MET exerted dose-related natriuretic and diuretic effects; intravenous doses of (-)E were more effective than (-)MET. The effects of (-)E and (-)MET on serum uric acid were the same as those reported with indacrinone. After (-)E, both (-)E and generated (-)MET appeared to contribute to the natriuresis. (+)E induced dose-related decreases in serum uric acid up to 24 hr after dosage; at the higher doses of (+)E, the hypouricemic effects were of the order of those after 500 mg of probenecid. Thus, indacrinone is a novel loop diuretic with enantiomers and a (-)MET, each of which has a different pharmacologic profile.
D000328:Adult; D004232:Diuretics / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D006900:Hydroxylation; D007189:Indans / Q000378:metabolism / Q000494:pharmacology*; D007192:Indenes / Q000494:pharmacology*; D007700:Kinetics; D008297:Male; D011188:Potassium / Q000652:urine; D012964:Sodium / Q000652:urine; D013237:Stereoisomerism; D014527:Uric Acid / Q000378:metabolism
D004232:Diuretics; D007189:Indans; D007192:Indenes; D014527:Uric Acid; D012964:Sodium; C013352:indacrinone; D011188:Potassium