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Chemical Compound Review

Zaroxolyn     7-chloro-2-methyl-3-(2- methylphenyl)-4-oxo...

Synonyms: Metenix, Metalazone, Metalozone, Metolazona, Microx, ...
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Disease relevance of metolazone


High impact information on metolazone

  • Metolazone for severe dilated cardiomyopathy refractory to conventional therapy [5].
  • We observed that elimination of glycosylation sites in flounder NCC did not affect the affinity of the cotransporter for metolazone [6].
  • Also, swapping the amino-terminal domain, the carboxyl-terminal domain, the glycosylation sites, or the entire extracellular glycosylation loop between rat and flounder NCC had no effect upon ions or metolazone affinity [6].
  • The function of the Na(+):K(+):2Cl(-) cotransporter was not affected by extracellular pH or by the addition of metolazone, 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DIDS), or R(+)-[(2-n-butyl-6,7-dichloro-2-cyclopentyl-2,3-dihydro-1-oxo-1-H-indenyl-5-yl)-oxy]acetic acid (DIOA) to the extracellular medium [7].
  • Injection of 10 ng of FLAG-tagged hNCC cRNA resulted in metolazone-sensitive (22)Na(+) uptake of 3.4 +/- 0.2 nmol Na(+)/oocyte per 2 h [8].

Chemical compound and disease context of metolazone


Biological context of metolazone


Anatomical context of metolazone


Associations of metolazone with other chemical compounds


Gene context of metolazone

  • Thus, while long-term treatment with metolazone inhibited the rise in urinary calcium excretion elicited by an oral calcium load, the effect was significant only in patients who had high baseline urinary calcium and PTH values [23].
  • The apparent Kd of metolazone for the renal PBR was 3.8 X 10(-7) M [24].

Analytical, diagnostic and therapeutic context of metolazone


  1. Hypoplastic anemia associated with metolazone. Suh, K., Sood, R. JAMA (1979) [Pubmed]
  2. Captopril/metolazone induced renal failure. Hogg, K.J., Hillis, W.S. Lancet (1986) [Pubmed]
  3. Furosemide-induced natriuresis as a test to identify cirrhotic patients with refractory ascites. Spahr, L., Villeneuve, J.P., Tran, H.K., Pomier-Layrargues, G. Hepatology (2001) [Pubmed]
  4. Metolazone and spironolactone in cirrhosis and the nephrotic syndrome. Lang, G.R., Westenfelder, C., Nascimento, L., Dhupelia, V.B., Arruda, J.A., Kane, R.E. Clin. Pharmacol. Ther. (1977) [Pubmed]
  5. Metolazone for severe dilated cardiomyopathy refractory to conventional therapy. Kröger, N., Szuba, J., Buhl, C., Pompecki, R., Frenzel, H. Lancet (1990) [Pubmed]
  6. Affinity-defining domains in the Na-Cl cotransporter: a different location for Cl- and thiazide binding. Moreno, E., Cristóbal, P.S., Rivera, M., Vázquez, N., Bobadilla, N.A., Gamba, G. J. Biol. Chem. (2006) [Pubmed]
  7. Functional properties of the apical Na+-K+-2Cl- cotransporter isoforms. Plata, C., Meade, P., Vazquez, N., Hebert, S.C., Gamba, G. J. Biol. Chem. (2002) [Pubmed]
  8. Functional expression of mutations in the human NaCl cotransporter: evidence for impaired routing mechanisms in Gitelman's syndrome. De Jong, J.C., Van Der Vliet, W.A., Van Den Heuvel, L.P., Willems, P.H., Knoers, N.V., Bindels, R.J. J. Am. Soc. Nephrol. (2002) [Pubmed]
  9. Combination diuretic treatment in severe heart failure: a randomised controlled trial. Channer, K.S., McLean, K.A., Lawson-Matthew, P., Richardson, M. British heart journal. (1994) [Pubmed]
  10. A comparison of the effects of chlorothiazide and of metolazone in the treatment of hypertension. Hua, A.S., Kincaid-Smith, P. Clinical science and molecular medicine. Supplement. (1976) [Pubmed]
  11. Toxic epidermal necrolysis. Lacy, J.A. Nutrition in clinical practice : official publication of the American Society for Parenteral and Enteral Nutrition. (1991) [Pubmed]
  12. Beneficial effects of metolazone in a rat model of preeclampsia. Pridjian, G., Pridjian, C., Danchuk, S., Ianosi-Irimie, M., Vu, H.V., Puschett, J.B. J. Pharmacol. Exp. Ther. (2006) [Pubmed]
  13. Thiazide diuretic receptors: autoradiographic localization in rat kidney with [3H]metolazone. Beaumont, K., Vaughn, D.A., Healy, D.P. J. Pharmacol. Exp. Ther. (1989) [Pubmed]
  14. Pharmacokinetic and pharmacodynamic interaction between furosemide and metolazone in man. Marone, C., Muggli, F., Lahn, W., Frey, F.J. Eur. J. Clin. Invest. (1985) [Pubmed]
  15. Alkalemia in diabetic ketoacidosis. Cronin, J.W., Kroop, S.F., Diamond, J., Rolla, A.R. Am. J. Med. (1984) [Pubmed]
  16. Direct effect of metolazone on sodium-dependent transport across the renal brush border membrane. Kempson, S.A., Kowalski, J.C., Puschett, J.B. J. Lab. Clin. Med. (1983) [Pubmed]
  17. Metolazone and axillary vein thrombosis. Green, S.T., Ng, J.P., Callaghan, M. Scottish medical journal. (1988) [Pubmed]
  18. Metolazone and bendroflumethiazide in hypertension: physiologic and metabolic observations. Winchester, J.F., Kellett, R.J., Boddy, K., Boyle, P., Dargie, H.J., Mahaffey, M.E., Ward, D.M., Kennedy, A.C. Clin. Pharmacol. Ther. (1980) [Pubmed]
  19. Do diuretics have antihypertensive properties independent of natriuresis? Bennett, W.M., McDonald, W.J., Kuehnel, E., Hartnett, M.N., Porter, G.A. Clin. Pharmacol. Ther. (1977) [Pubmed]
  20. Antihypertensive and renin angiotensin effects of metolazone with and without propranolol. Sambhi, M.P., Eggena, P., Barrett, J.D., Thananopavarn, C., Tuck, M., Wiedman, C. Journal of clinical pharmacology. (1977) [Pubmed]
  21. Insights into intrarenal sites and mechanisms of action of diuretic agents. Materson, B.J. Am. Heart J. (1983) [Pubmed]
  22. Double-blind comparison of losartan, lisinopril, and metolazone in elderly hypertensive patients with previous angiotensin-converting enzyme inhibitor-induced cough. Chan, P., Tomlinson, B., Huang, T.Y., Ko, J.T., Lin, T.S., Lee, Y.S. Journal of clinical pharmacology. (1997) [Pubmed]
  23. Changes in calcium excretion after prolonged metolazone therapy in recurrent stone formers. Lespier-Dexter, L.E., Martinez-Maldonado, M. Clin. Pharmacol. Ther. (1979) [Pubmed]
  24. Interactions of diuretics with the peripheral-type benzodiazepine receptor in rat kidney. Lukeman, D.S., Fanestil, D.D. J. Pharmacol. Exp. Ther. (1987) [Pubmed]
  25. Determination of the diuretic agent metolazone in plasma by high-performance liquid chromatography. Brodie, R.R., Chasseaud, L.F., Walmsley, L.M. J. Chromatogr. (1981) [Pubmed]
  26. Use of a bioassay in healthy men to evaluate diuretic-spironolactone combinations. McInnes, G.T., Shelton, J.R., Perkins, R.M., Harrison, I.R., Clarke, J.M. British journal of clinical pharmacology. (1983) [Pubmed]
  27. Determination of a Metolazone metabolite in human urine by high-performance liquid chromatography/diode-array detection, high-performance liquid chromatography/electrospray ionization mass spectrometry and gas chromatography/mass spectrometry. Kim, Y., Kim, S., Kim, M., Lee, W. Rapid Commun. Mass Spectrom. (2004) [Pubmed]
  28. Novel high-performance liquid chromatographic method using solid-phase on-line elution for determination of metolazone in plasma and whole blood. Farthing, D., Sica, D.A., Fakhry, I., Gehr, T.W. J. Chromatogr. B, Biomed. Appl. (1994) [Pubmed]
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