Bemitradine (SC-33643), a diuretic antihypertensive agent that was dropped from the development. Experiments on rodents have revealed this drug was a carcinogen and acted by a hormonally modulated promotional activity in inducing tumors in the liver and mammary glands.

Tizolemide is a sulphonamide diuretic. The effect on transepithelial Na transport of tizolemide was investigated in isolated frog skin (Rana temporaria). It was found that tizolemide (2-5 mM, serosal side) decreased transepithelial Na transport (measured as short circuit current and as net sodium flux) within 60 min to 25-40% of the control level resulting from reduction of the unidirectional sodium influx. Tizolemide has alkaline properties and is cleared by a tubular transport system which differs from the PAH-excreting system which transports thiazide diuretics. Tizolemide was almost completely absorbed from the gastrointestinal tract. The drug was mainly eliminated via tubular secretion. Renal clearance of the drug was much lower in patients with compensated cardiac failure than in healthy subjects because of low renal plasma flow. As a consequence, plasma half-life was prolonged considerably in some patients. It was concluded that drugs with mainly tubular renal elimination may have a reduced elimination rate in patients with cardiac diseases despite normal glomerular filtration rate.

Furterene is a diuretic of the aminopteridine series, with aldosterone antagonist activity. Furterene is able to antagonize aldosterone at the mineralocorticoid receptor in the kidneys. It thereby increases sodium excretion while inhibiting potassium excretion.

Triflocin is a nicotinic acid derivative. Triflocin is a diuretic agent. It is structurally dissimilar from ethacrynic acid and furosemide although their natriuretic potency and site of action in the kidney appear similar. Triflocin inhibits sodium-stimulated, ouabain-insensitive ATPase. In vivo, a natriuretic effect of Triflocin has been reported in both the proximal convoluted tubule and the thick ascending limb of Henle's loop. Upon acute isohydric hypercapnia, Triflocin depolarizes the basolateral membrane potential. Triflocin inhibits the basolateral electrogenic Na-(HCO3)n > 1 cotransport in proximal tubules.

Indacrinone is an orally active, indanone-based loop diuretic patented by American pharmaceutical company Merck and Co as mixture of two enantiomers. In healthy volunteers, the racernic mixture of indacrinone exhibited greater natriuretic potency than furosemide, with a slower onset and longer duration of action. Furthermore, single doses of indacrinone decreased serum uric acid concentrations and increased uric acid clearance, while similar doses of furosemide generally had the opposite effects. Differences in the pharmacologic effects of the resolved enantiomers of indacrinone were initially studied in animals and confirmed in a series of studies we conducted in healthy human volunteer. The S( + ) form is a potent uricosuric agent that produces mild natriuresis only at higher doses, while the R( - ) form is a potent loop diuretic with only transient uricosuric effects. The (-) enantiomer and its active metabolite appear to be primarily responsible for the natriuretic effects of the racemic mixture; the ( + ) enantiomer is 20-40 times less potent a natriuretic agent.

Alipamide is an antihypertensive and diuretic agent. It is a hydrazide derivative of m-sulfamoylbenzoic acid with diuretic activity. Alipamide primarily causes a saluretic effect and is able to inhibit carbonic anhydrase at higher doses which may also contribute to this agent's diuretic effect.

RU 28318 also known as OXPRENOATE is a mineralocorticoid receptor (MR) antagonist, inhibiting aldosterone production and secretion. RU 28318 has been studied in normal and diabetic rats. It was revealed, that in combination with angiotensin converting enzyme inhibitors, RU 28318 was the most effective at improving -dP/dt (a measure of diastolic function) and attenuated cardiac dysfunction in diabetes.

Ticrynafen, or tienilic acid, is a diuretic drug with uric acid-lowering action, formerly marketed for the treatment of hypertension. It was withdrawn from the market only months after its introduction because of reports of serious incidents of drug-induced liver injury including some fatalities. Its hepatotoxicity is considered to be primarily immunoallergic in nature. Tienilic acid is a thiophene-containing mechanism-based inactivator of P450 2C9, resulting from covalent modification of the P450 2C9 protein. The bioactivation mechanism involves oxidation of the thiophene ring system.