: 127   Other diuretics cause a decrease in the sodium concentration of the forming urine due to the entry of sodium into the cell via the ENaC, and the concomitant exit of potassium from the principal cell into the forming urine. Blocking ENaC prevents this from happening. Amiloride works in the same way. Sodium channel blockers directly inhibit the entry of sodium into the sodium channels. With hydrochlorothiazide
Triamterene is commonly prepared in combination with hydrochlorothiazide for treatment of hypertension (high blood pressure) and edema (water retention). This combination is in a class of medications called diuretics or water pills, and causes the kidneys to get rid of the bodys unneeded water and sodium through the urine. History
The triamterene ring system is found in many naturally occurring compounds, such as folic acid and riboflavin. The observation that the naturally occurring compound xanthopterin had renal affects led scientists at Smith Kline and French Laboratories in Philadelphia to begin a medicinal chemistry campaign to discover potential drugs, as part of a program to discover potassium-sparing diuretics. : 125   The first clinical studies were published in 1961 and the first trials combining it with hydrochlorothiazide were published the next year. : 126 Smith Kline & French launched it as a single agent under the brand Dyrenium in 1964.: 83   The combination drug with hydrochlorothiazide, Dyazide, was first approved in the US in 1965 and the first generic, brought by Bolar Pharmaceutical Co., was approved in 1987.
The reduction to alcohol is performed with a derivative of a borohydride of an alkali metal with formula MHBL3, where M=Li, Na, K; L=AlkO, AlkCOO, ArCOO. The subsequent halogenation is performed with a complex halogenating agent where an H or a chain of up to 4 carbons is combined with Cl, I or Br. The final hydrolysis is analogous to the one in the first pathway. Development history
The first trial of epirubicin in humans was published in 1980. Upjohn applied for approval by the U.S. Food and Drug Administration (FDA) in node-positive breast cancer in 1984, but was turned down because of lack of data. In 1999 Pharmacia (who had by then merged with Upjohn) received FDA approval for the use of epirubicin as a component of adjuvant therapy in node-positive patients. Patent protection for epirubicin expired in August 2007. == References ==