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Chemical Compound Review

chlorothiazide     4-chloro-10,10-dioxo- 10$l^{6}-thia-7,9...

Synonyms: Aldoclor, Chlrosal, Clotride, Diuresal, Diurilix, ...
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Disease relevance of chlorothiazide


Psychiatry related information on chlorothiazide

  • MEASUREMENTS: Bone mass and environmental characteristics (cigarette smoking, alcohol consumption, physical activity, dietary calcium intake, use of thiazide diuretics) measured at baseline and 16 years later [6].
  • Coronary risk reduction has been disappointing when blood pressure has been lowered with treatment regimens based on thiazide diuretics and/or beta blockers [7].
  • RESULTS: When the data were analyzed by the intention-to-treat paradigm (ignoring changes in therapy), glucose and cholesterol levels in the thiazide group were significantly higher (compared to baseline or to the other therapy group) only at year 1 [8].
  • There is no substantial evidence that l-dopa or histamine-2-receptor blockers cause depression and the literature is relatively conclusive in determining that thiazide diuretics are not associated with depressive symptoms [9].
  • However, based on our study we do not recommend treatment with thiazide diuretics in all patients diagnosed with hypercalciuria, as hematuria resolved in a majority with observation or expectant treatment and minor dietary modification [10].

High impact information on chlorothiazide


Chemical compound and disease context of chlorothiazide


Biological context of chlorothiazide


Anatomical context of chlorothiazide

  • Estradiol enhances thiazide-sensitive NaCl cotransporter density in the apical plasma membrane of the distal convoluted tubule in ovariectomized rats [24].
  • We report here that [3H]metolazone, a diuretic with a thiazide-like mechanism of action, labels a site in rat kidney membranes that has characteristics of the thiazide-sensitive ion transporter [25].
  • Calcium antagonists and certain smooth muscle relaxants had Ki values of 0.6-10 microM for these low-affinity sites, which were not inhibited by most of the thiazide diuretics tested [25].
  • Although recent reports found that expression of WNK4 in Xenopus oocytes causes inhibition of the thiazide-sensitive NaCl cotransporter and the renal K channel ROMK, there may be additional targets of WNK4 [26].
  • At the time papillary plasma flow was measured, extracellular fluid volume was similar among the four groups of dogs; however, plasma renin activity increased significantly in furosemide and ethacrynic acid dogs (P less than 0.01) and remained unchanged in normal and chlorothiazide dogs [27].

Associations of chlorothiazide with other chemical compounds


Gene context of chlorothiazide


Analytical, diagnostic and therapeutic context of chlorothiazide


  1. Hypertension and antihypertensive therapy as risk factors for type 2 diabetes mellitus. Atherosclerosis Risk in Communities Study. Gress, T.W., Nieto, F.J., Shahar, E., Wofford, M.R., Brancati, F.L. N. Engl. J. Med. (2000) [Pubmed]
  2. Gitelman's variant of Bartter's syndrome, inherited hypokalaemic alkalosis, is caused by mutations in the thiazide-sensitive Na-Cl cotransporter. Simon, D.B., Nelson-Williams, C., Bia, M.J., Ellison, D., Karet, F.E., Molina, A.M., Vaara, I., Iwata, F., Cushner, H.M., Koolen, M., Gainza, F.J., Gitleman, H.J., Lifton, R.P. Nat. Genet. (1996) [Pubmed]
  3. Diuretic therapy for hypertension and the risk of primary cardiac arrest. Siscovick, D.S., Raghunathan, T.E., Psaty, B.M., Koepsell, T.D., Wicklund, K.G., Lin, X., Cobb, L., Rautaharju, P.M., Copass, M.K., Wagner, E.H. N. Engl. J. Med. (1994) [Pubmed]
  4. Thiazide, diuretics, cholecystitis, and pancreatitis. Bourke, J.B., Langman, M.J. N. Engl. J. Med. (1981) [Pubmed]
  5. Thiazides and acute cholecystitis. Rosenberg, L., Shapiro, S., Slone, D., Kaufman, D.W., Miettinen, O.S., Stolley, P.D. N. Engl. J. Med. (1980) [Pubmed]
  6. Long-term bone loss in men: effects of genetic and environmental factors. Slemenda, C.W., Christian, J.C., Reed, T., Reister, T.K., Williams, C.J., Johnston, C.C. Ann. Intern. Med. (1992) [Pubmed]
  7. Epidemiologic and clinical aspects of insulin resistance and hyperinsulinemia. Flack, J.M., Sowers, J.R. Am. J. Med. (1991) [Pubmed]
  8. Glucose and cholesterol elevations during thiazide therapy: intention-to-treat versus actual on-therapy experience. Elliott, W.J. Am. J. Med. (1995) [Pubmed]
  9. Drug-induced depression. Patten, S.B., Love, E.J. Psychotherapy and psychosomatics. (1997) [Pubmed]
  10. The association of an increased urinary calcium-to-creatinine ratio, and asymptomatic gross and microscopic hematuria in children. Parekh, D.J., Pope, J.C., Adams, M.C., Brock, J.W. J. Urol. (2002) [Pubmed]
  11. Multilocus linkage of familial hyperkalaemia and hypertension, pseudohypoaldosteronism type II, to chromosomes 1q31-42 and 17p11-q21. Mansfield, T.A., Simon, D.B., Farfel, Z., Bia, M., Tucci, J.R., Lebel, M., Gutkin, M., Vialettes, B., Christofilis, M.A., Kauppinen-Makelin, R., Mayan, H., Risch, N., Lifton, R.P. Nat. Genet. (1997) [Pubmed]
  12. Thiazide effect on the mineral content of bone. Wasnich, R.D., Benfante, R.J., Yano, K., Heilbrun, L., Vogel, J.M. N. Engl. J. Med. (1983) [Pubmed]
  13. Furosemide promotes patent ductus arteriosus in premature infants with the respiratory-distress syndrome. Green, T.P., Thompson, T.R., Johnson, D.E., Lock, J.E. N. Engl. J. Med. (1983) [Pubmed]
  14. Response of thiazide-induced hypokalemia to amiloride. Maronde, R.F., Milgrom, M., Vlachakis, N.D., Chan, L. JAMA (1983) [Pubmed]
  15. Primary prevention with metoprolol in patients with hypertension. Mortality results from the MAPHY study. Wikstrand, J., Warnold, I., Olsson, G., Tuomilehto, J., Elmfeldt, D., Berglund, G. JAMA (1988) [Pubmed]
  16. Evaluation of a new uricosuric diuretic--ticrynafen. Kosman, M.E. JAMA (1979) [Pubmed]
  17. Patient acceptance of guanethidine as therapy for mild to moderate hypertension. A comparison with reserpine. Ferguson, R.K., Rothenberg, R.J., Nies, A.S. Circulation (1976) [Pubmed]
  18. Influence of thiazide on salt hypertension. Iwai, J., Ohanian, E.V., Dahl, L.K. Circ. Res. (1977) [Pubmed]
  19. Step 2 regimens in hypertension. An assessment. Finnerty, F.A., Gyftopoulos, A., Berry, C., McKenney, A. JAMA (1979) [Pubmed]
  20. Systolic hypertension in the elderly. Hemodynamic response to long-term thiazide diuretic therapy and its side effects. Vardan, S., Mookherjee, S., Warner, R., Smulyan, H. JAMA (1983) [Pubmed]
  21. Expression of the thiazide-sensitive Na-Cl cotransporter by rabbit distal convoluted tubule cells. Bachmann, S., Velázquez, H., Obermüller, N., Reilly, R.F., Moser, D., Ellison, D.H. J. Clin. Invest. (1995) [Pubmed]
  22. WNK kinases regulate thiazide-sensitive Na-Cl cotransport. Yang, C.L., Angell, J., Mitchell, R., Ellison, D.H. J. Clin. Invest. (2003) [Pubmed]
  23. Response of blood pressure, cardiac output, peripheral resistance, and exercise performance to substitution of calcium blocker for beta-blocker plus thiazide diuretic therapy in patients with both systemic hypertension and mild stable angina. Kawanishi, D.T., Reid, C.L., Gonzales, A., O'Rourke, R.A., Rahimtoola, S.H. Circulation (1989) [Pubmed]
  24. Estradiol enhances thiazide-sensitive NaCl cotransporter density in the apical plasma membrane of the distal convoluted tubule in ovariectomized rats. Verlander, J.W., Tran, T.M., Zhang, L., Kaplan, M.R., Hebert, S.C. J. Clin. Invest. (1998) [Pubmed]
  25. Thiazide diuretic drug receptors in rat kidney: identification with [3H]metolazone. Beaumont, K., Vaughn, D.A., Fanestil, D.D. Proc. Natl. Acad. Sci. U.S.A. (1988) [Pubmed]
  26. Disease-causing mutant WNK4 increases paracellular chloride permeability and phosphorylates claudins. Yamauchi, K., Rai, T., Kobayashi, K., Sohara, E., Suzuki, T., Itoh, T., Suda, S., Hayama, A., Sasaki, S., Uchida, S. Proc. Natl. Acad. Sci. U.S.A. (2004) [Pubmed]
  27. Effects of diuretics on inner medullary hemodynamics in the dog. Spitalewitz, S., Chou, S.Y., Faubert, P.F., Porush, J.G. Circ. Res. (1982) [Pubmed]
  28. Clarification of the site of action of chlorothiazide in the rat nephron. Kunau, R.T., Weller, D.R., Webb, H.L. J. Clin. Invest. (1975) [Pubmed]
  29. Site and mechanism of action of trichlormethiazide in rabbit distal nephron segments perfused in vitro. Shimizu, T., Yoshitomi, K., Nakamura, M., Imai, M. J. Clin. Invest. (1988) [Pubmed]
  30. Effects of thiazide diuretics on plasma lipids and lipoproteins in mildly hypertensive patients: a double-blind controlled trial. Grimm, R.H., Leon, A.S., Hunninghake, D.B., Lenz, K., Hannan, P., Blackburn, H. Ann. Intern. Med. (1981) [Pubmed]
  31. Antihypertensive drug therapy prevents cerebral microvascular abnormalities in hypertensive rats. Harper, S.L. Circ. Res. (1987) [Pubmed]
  32. Mechanisms of WNK1 and WNK4 interaction in the regulation of thiazide-sensitive NaCl cotransport. Yang, C.L., Zhu, X., Wang, Z., Subramanya, A.R., Ellison, D.H. J. Clin. Invest. (2005) [Pubmed]
  33. Role of HSD11B2 polymorphisms in essential hypertension and the diuretic response to thiazides. Williams, T.A., Mulatero, P., Filigheddu, F., Troffa, C., Milan, A., Argiolas, G., Parpaglia, P.P., Veglio, F., Glorioso, N. Kidney Int. (2005) [Pubmed]
  34. Axial heterogeneity of vasopressin-receptor subtypes along the human and mouse collecting duct. Carmosino, M., Brooks, H.L., Cai, Q., Davis, L.S., Opalenik, S., Hao, C., Breyer, M.D. Am. J. Physiol. Renal Physiol. (2007) [Pubmed]
  35. Molecular cloning, expression pattern, and chromosomal localization of the human Na-Cl thiazide-sensitive cotransporter (SLC12A3). Mastroianni, N., De Fusco, M., Zollo, M., Arrigo, G., Zuffardi, O., Bettinelli, A., Ballabio, A., Casari, G. Genomics (1996) [Pubmed]
  36. Low-dose hydrochlorothiazide and preservation of bone mineral density in older adults. A randomized, double-blind, placebo-controlled trial. LaCroix, A.Z., Ott, S.M., Ichikawa, L., Scholes, D., Barlow, W.E. Ann. Intern. Med. (2000) [Pubmed]
  37. Thiazide-induced hyponatremia. Reproducibility by single dose rechallenge and an analysis of pathogenesis. Friedman, E., Shadel, M., Halkin, H., Farfel, Z. Ann. Intern. Med. (1989) [Pubmed]
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