interstitium. Thus, intracellular Ca2+ concentration is decreased, which allows more Ca2+ from the lumen of the tubules to enter epithelial cells via apical Ca2+-selective channels (TRPV5). In other words, less Ca2+ in the cell increases the driving force for reabsorption from the lumen. Thiazides are also thought to increase the reabsorption of Ca2+ by a mechanism involving the reabsorption of sodium and calcium in the proximal tubule in response to sodium depletion. Some of this response is due to augmentation of the action of parathyroid hormone. Breastfeeding Thiazides pass into breast milk and can decrease the flow of breast milk. Thiazides have been associated with significant side effects in some nursing infants and should be administered to nursing mothers with caution. History The thiazide diuretics were developed by scientists Karl H. Beyer, James M. Sprague, John E. Baer, and Frederick C. Novello of Merck and Co. in the 1950s, and led to the marketing of the first drug of this class, chlorothiazide, under the trade name Diuril in 1958. The research leading to the discovery of chlorothiazide, leading to "the saving of untold thousands of lives and the alleviation of the suffering of millions of victims of hypertension" was recognized by a special Public Health Award from the Lasker Foundation in 1975. References World Anti-Doping Agency prohibited substances Nephrotoxins