Chemistry and pharmacological properties of the pyridine-3-sulfonylurea derivative torasemide.
Out of a series of pyridine-3-sulfonylureas with diuretic activity torasemide (1-isopropyl-3- ([4-(3-methyl-phenylamino)pyridine]-3-sulfonyl)urea) has been proved to be one of the most active derivatives. In the rat, urinary volume and electrolyte excretions increased linearily with the logarithm of the dose, thus resembling the profile of a high ceiling diuretic. Experiments by oral and intravenous routes indicated that torasemide was equally potent both by oral and parenteral administration. Compared to furosemide, torasemide was 9-40 times more potent on weight basis in the rat. For the same natriuretic effect, however, potassium losses with torasemide were significantly less than with furosemide. The diuretic effect of torasemide lasted longer compared to that of furosemide. In accordance with the pharmacodynamic characteristics plasma elimination half-life of torasemide was about 1.5 h in the rat and bioavailability was nearly complete. Torasemide was 98-99% bound to plasma proteins. No in vitro interaction was found with the cumarine derivative warfarin.
Delarge
J
J
Department of Medicinal Chemistry, State University of Liège, Belgium.
D000818:Animals; D001798:Blood Proteins / Q000378:metabolism; D055598:Chemical Phenomena; D002621:Chemistry; D004232:Diuretics / Q000032:analysis* / Q000493:pharmacokinetics / Q000494:pharmacology; D005665:Furosemide / Q000494:pharmacology; D007275:Injections, Intravenous; D008297:Male; D010653:Phenylbutazone / Q000494:pharmacology; D011485:Protein Binding; D051381:Rats; D011919:Rats, Inbred Strains; D013449:Sulfonamides / Q000032:analysis* / Q000493:pharmacokinetics / Q000494:pharmacology; D000077786:Torsemide
D001798:Blood Proteins; D004232:Diuretics; D013449:Sulfonamides; D005665:Furosemide; D010653:Phenylbutazone; D000077786:Torsemide