Amiloride, as a pure substance, is highly fluorescent, with excitation wavelengths at 215, 288, and 360 nm, emitting light at 420 nm. History Amiloride was first synthesized and discovered by the Merck Sharp and Dohme Research Laboratories in the late 1960s. The drug was discovered as part of a screening process of chemicals that reversed the effects of mineralocorticoids in vivo. Amiloride was the only drug in the screen that was capable of causing the excretion of sodium (natriuresis) without a concomitant urinary excretion of potassium (kaliuresis). Thousands of amiloride analogues have been studied since its initial discovery, which have been used to study the effects of sodium transporters. Amiloride was approved by the U.S. Food and Drug Administration (FDA) on October 5, 1981. Society and culture It is on the World Health Organization's List of Essential Medicines. Amiloride is on the World Anti-Doping Agency's list of banned substances, as it is considered a masking agent. Diuretics like amiloride act as masking agents by reducing the concentration of other doping agents due to promoting diuresis, increasing the total volume of the urine. The list includes other potassium-sparing diuretics, such as triamterene and spironolactone. In 2008, amiloride and the potassium-sparing diuretic triamterene were found in 3% of positive diuretic doping samples. Formulations and trade names Amiloride hydrochloride Midamor (U.S.) Co-amilozide (amiloride hydrochloride with hydrochlorothiazide) Co-amilofruse (amiloride hydrochloride with furosemide) Amiloride hydrochloride with cyclopenthiazide Amiloride hydrochloride with bumetanide Research Amiloride is an inhibitor of NHE-1, which helps to maintain normal pH within cells. Cancer cells in leukemia, a type of blood cancer, have higher pH compared to normal cells. Amiloride affects the splicing and regulation of multiple genes involved in cancer, though they do not appear to be directly related to its effects on pH. Amiloride has been tested in vitro as an adjunct to the anticancer drug imatinib, which appeared to show a synergistic effect. Modified versions of amiloride, known as 5'-(N,N-dimethyl)-amiloride (DMA), 5-N-ethyl-N-isopropyl amiloride (EIPA), and 5-(N,N-hexamethylene)-amiloride (HMA), are being studied for the treatment of leukemia. Cystic fibrosis is a genetic disorder due to a mutation in the CFTR gene, which encodes for the CFTR chloride channel. There is evidence that suggests that the molecular target of amiloride, ENaC, is also implicated in cystic fibrosis due to its effects on mucus in the lungs. Aerosolized formulations of amiloride have been tested in clinical trials, though long-term clinical trials have failed