Chlorthalidone Impurity G

Chlorthalidone impurity G is a potential impurity found in commercial preparations of chlorthalidone that has moderate antihypertensive effects.¹ Chlorthalidone is a thiazide-like diuretic that inhibits the Na⁺/Cl^- cotransporter in the distal convoluted tubule of the kidney, which prevents reabsorption of sodium and chloride leading to a reduction in plasma volume and cardiac output.² It also inhibits carbonic anhydrase (CA), including the isoforms CAVB, VII, IX, XII, and XIII (K_is = 2.8-23 nM) and, to a lesser extent, CAI, CAII, IV, VA, and VI (K_is = 138-1,347 nM), which may mediate its sustained vasodilatory activity.³ Dietary administration of chlorthalidone (8 mg per animal per day) reduces arterial hypertension and prevents or reduces ventricular hypertrophy in DOCA-salt hypertensive rats.⁴ Formulations containing chlorthalidone have been used alone or in combination with other antihypertensive agents to lower arterial blood pressure and as adjuvants to address edema caused by cardiac or renal disorders.

WARNING This product is not for human or veterinary use.

1. Topliss, J.G., Konzelman, L.M., Sperber, N., et al. Antihypertensive agents. III. 3-Hydroxy-3-phenylphthalimidines. J. Med. Chem. 7, 453-456 (1964).

2. Roush, G.C., Buddharaju, V., Ernst, M.E., et al. Chlorthalidone: Mechanisms of action and effect on cardiovascular events. Curr. Hypertens. Rep. 15(5), 514-521 (2013).

3. Temperini, C., Cecchi, A., Scozzafava, A., et al. Carbonic anhydrase inhibitors. Interaction of indapamide and related diuretics with 12 mammalian isozymes and X-ray crystallographic studies for the indapamide-isozyme II adduct. Bioorg. Med. Chem. Lett. 18(8), 2567-2573 (2008).

4. Cabral, A.M., Carvalhinho, F.B., Vasquez, E.C., et al. Effects of chlorthalidone on ventricular hypertrophy in deoxycorticosterone acetate-salt hypertensive rats. Hypertension 23(1 Suppl), I180-I184 (1994).