Chlorthalidone
(Synonyms: 氯噻酮) 目录号 : GC35681
A thiazide-like diuretic
Cas No.:77-36-1
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
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.1 It also inhibits carbonic anhydrase (CA), including the isoforms CAVB, VII, IX, XII, and XIII (Kis = 2.8-23 nM) and, to a lesser extent, CAI, CAII, IV, VA, and VI (Kis = 138-1,347 nM), which may mediate its sustained vasodilatory activity.2 Dietary administration of chlorthalidone (8 mg per animal per day) reduces arterial hypertension and prevents or reduces ventricular hypertrophy in DOCA-salt hypertensive rats.3 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.
1.Roush, G.C., Buddharaju, V., Ernst, M.E., et al.Chlorthalidone: Mechanisms of action and effect on cardiovascular eventsCurr. Hypertens. Rep.15(5)514-521(2013) 2.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 adductBioorg. Med. Chem. Lett.18(8)2567-2573(2008) 3.Cabral, A.M., Carvalhinho, F.B., Vasquez, E.C., et al.Effects of chlorthalidone on ventricular hypertrophy in deoxycorticosterone acetate-salt hypertensive ratsHypertension23(1 Suppl)I180-I184(1994)
| Cas No. | 77-36-1 | SDF | |
| 别名 | 氯噻酮 | ||
| Canonical SMILES | O=S(C1=CC(C2(O)NC(C3=C2C=CC=C3)=O)=CC=C1Cl)(N)=O | ||
| 分子式 | C14H11ClN2O4S | 分子量 | 338.77 |
| 溶解度 | DMSO: ≥ 41 mg/mL (121.03 mM) | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.9519 mL | 14.7593 mL | 29.5186 mL |
| 5 mM | 0.5904 mL | 2.9519 mL | 5.9037 mL |
| 10 mM | 0.2952 mL | 1.4759 mL | 2.9519 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Comparison of Cardiovascular and Safety Outcomes of Chlorthalidone vs Hydrochlorothiazide to Treat Hypertension
JAMA Intern Med 2020 Apr 1;180(4):542-551.PMID:32065600DOI:10.1001/jamainternmed.2019.7454.
Importance: Chlorthalidone is currently recommended as the preferred thiazide diuretic to treat hypertension, but no trials have directly compared risks and benefits. Objective: To compare the effectiveness and safety of Chlorthalidone and hydrochlorothiazide as first-line therapies for hypertension in real-world practice. Design, setting, and participants: This is a Large-Scale Evidence Generation and Evaluation in a Network of Databases (LEGEND) observational comparative cohort study with large-scale propensity score stratification and negative-control and synthetic positive-control calibration on databases spanning January 2001 through December 2018. Outpatient and inpatient care episodes of first-time users of antihypertensive monotherapy in the United States based on 2 administrative claims databases and 1 collection of electronic health records were analyzed. Analysis began June 2018. Exposures: Chlorthalidone and hydrochlorothiazide. Main outcomes and measures: The primary outcomes were acute myocardial infarction, hospitalization for heart failure, ischemic or hemorrhagic stroke, and a composite cardiovascular disease outcome including the first 3 outcomes and sudden cardiac death. Fifty-one safety outcomes were measured. Results: Of 730 225 individuals (mean [SD] age, 51.5 [13.3] years; 450 100 women [61.6%]), 36 918 were dispensed or prescribed Chlorthalidone and had 149 composite outcome events, and 693 337 were dispensed or prescribed hydrochlorothiazide and had 3089 composite outcome events. No significant difference was found in the associated risk of myocardial infarction, hospitalized heart failure, or stroke, with a calibrated hazard ratio for the composite cardiovascular outcome of 1.00 for Chlorthalidone compared with hydrochlorothiazide (95% CI, 0.85-1.17). Chlorthalidone was associated with a significantly higher risk of hypokalemia (hazard ratio [HR], 2.72; 95% CI, 2.38-3.12), hyponatremia (HR, 1.31; 95% CI, 1.16-1.47), acute renal failure (HR, 1.37; 95% CI, 1.15-1.63), chronic kidney disease (HR, 1.24; 95% CI, 1.09-1.42), and type 2 diabetes mellitus (HR, 1.21; 95% CI, 1.12-1.30). Chlorthalidone was associated with a significantly lower risk of diagnosed abnormal weight gain (HR, 0.73; 95% CI, 0.61-0.86). Conclusions and relevance: This study found that Chlorthalidone use was not associated with significant cardiovascular benefits when compared with hydrochlorothiazide, while its use was associated with greater risk of renal and electrolyte abnormalities. These findings do not support current recommendations to prefer Chlorthalidone vs hydrochlorothiazide for hypertension treatment in first-time users was found. We used advanced methods, sensitivity analyses, and diagnostics, but given the possibility of residual confounding and the limited length of observation periods, further study is warranted.
Chlorthalidone: the forgotten diuretic
Postgrad Med 2012 Jan;124(1):60-6.PMID:22314115DOI:10.3810/pgm.2012.01.2518.
Chlorthalidone's safety and efficacy in the management of hypertension has been demonstrated in landmark trials. Despite understanding the effects of thiazides on urinary sodium excretion and intravascular volume, the exact mechanism of their antihypertensive effects is not clearly understood. Common compensatory mechanisms for decreases in circulating plasma volume include increased adrenergic tone and systemic vascular resistance, as well as increases in the renin-angiotensin-aldosterone system. Chlorthalidone has been shown to decrease platelet aggregation and vascular permeability and promote angiogenesis in vitro, which is thought to be, in part, the result of reductions in carbonic anhydrase-dependent pathways, including catecholamine-mediated platelet aggregation and downregulation of VEGF-C gene expression. This article reviews the comparative clinical data between Chlorthalidone and hydrochlorothiazide, the pharmacologic properties that might explain some of their differences regarding half-life and efficacy, and what is known about the effect of Chlorthalidone on intermediate endpoints.
Should Chlorthalidone be the diuretic of choice for antihypertensive therapy?
Curr Hypertens Rep 2008 Aug;10(4):293-7.PMID:18625158DOI:10.1007/s11906-008-0054-6.
For decades, diuretic therapy has been a cornerstone in treating hypertension, an approach supported by multiple randomized controlled trials demonstrating reduced morbidity and mortality from cardiovascular events. Yet controversy persists regarding the potential detrimental metabolic effects and side effects of diuretic agents. Within the risk-benefit debates about diuretic therapy is a second dialogue regarding the best thiazide or thiazidelike agent to prescribe. Proponents of Chlorthalidone emphasize the demonstrated reductions in cardiovascular events reported from multiple classic trials and its longer half-life, whereas opponents point to its limited availability in low-dose forms and comparable favorable results from hydrochlorothiazide-based therapy to discredit claims of superiority. This review presents the data available on both sides of this issue to help the reader decide which claims are most valid, and offers recommendations for treatment.
Comparison of Clinical Outcomes and Safety Associated With Chlorthalidone vs Hydrochlorothiazide in Older Adults With Varying Levels of Kidney Function
JAMA Netw Open 2021 Sep 1;4(9):e2123365.PMID:34524440DOI:10.1001/jamanetworkopen.2021.23365.
Importance: Thiazide diuretics are commonly prescribed for the treatment of hypertension, a disease highly prevalent among older individuals and in those with chronic kidney disease. How specific thiazide diuretics compare in regard to safety and clinical outcomes in these populations remains unknown. Objective: To compare safety and clinical outcomes associated with Chlorthalidone or hydrochlorothiazide use among older adults with varying levels of kidney function. Design, setting, and participants: This population-based retrospective cohort study was conducted in Ontario, Canada, from 2007 to 2015. Participants included adults aged 66 years or older who initiated Chlorthalidone or hydrochlorothiazide during this period. Data were analyzed from December 2019 through September 2020. Exposures: New Chlorthalidone users were matched 1:4 with new hydrochlorothiazide users by a high-dimensional propensity score. Time-to-event models accounting for competing risks examined the associations between Chlorthalidone vs hydrochlorothiazide use and the outcomes of interest overall and within estimated glomerular filtration rate (eGFR) categories (≥60, 45-59, and <45 mL/min/1.73 m2). Main outcomes and measures: The outcomes of interest were adverse kidney events (ie, eGFR decline ≥30%, dialysis, or kidney transplantation), cardiovascular events (composite of myocardial infarction, coronary revascularization, heart failure, or atrial fibrillation), all-cause mortality, and electrolyte anomalies (ie, sodium or potassium levels outside reference ranges). Results: After propensity score matching, the study cohort included 12 722 adults (mean [SD] age, 74 [7] years; 7063 [56%] women; 5659 [44%] men; mean [SD] eGFR, 69 [19] mL/min/1.73 m2), including 2936 who received Chlorthalidone and 9786 who received hydrochlorothiazide. Chlorthalidone use was associated with a higher risk of eGFR decline of 30% or greater (hazard ratio [HR], 1.24 [95% CI, 1.13-1.36]) and cardiovascular events (HR, 1.12 [95% CI, 1.04-1.22]) across all eGFR categories compared with hydrochlorothiazide use. Chlorthalidone use was also associated with a higher risk of hypokalemia compared with hydrochlorothiazide use, which was more pronounced among those with higher eGFR (eGFR ≥60 mL/min/1.73 m2: HR, 1.86 [95% CI, 1.67-2.08]; eGFR 45-59 mL/min/1.73 m2: HR, 1.57 [95% CI, 1.25-1.96]; eGFR <45 mL/min/1.73 m2: HR, 1.10 [95% CI, 0.84-1.45]; P for interaction = .001). No significant differences were observed between Chlorthalidone and hydrochlorothiazide for dialysis or kidney transplantation (HR, 1.44 [95% CI, 0.88-2.36]), all-cause mortality (HR, 1.10 [95% CI, 0.93-1.29]), hyperkalemia (HR, 1.05 [95% CI, 0.79-1.39]), or hyponatremia (HR, 1.14 [95% CI, CI 0.98-1.32]). Conclusions and relevance: This cohort study found that among older adults, Chlorthalidone use was associated with a higher risk of eGFR decline, cardiovascular events, and hypokalemia compared with hydrochlorothiazide use. The excess risk of hypokalemia with Chlorthalidone was attenuated in participants with reduced kidney function. Placed in context with prior observational studies comparing the safety and clinical outcomes associated with thiazide diuretics, these results suggest that there is no evidence to prefer Chlorthalidone over hydrochlorothiazide.
Chlorthalidone: mechanisms of action and effect on cardiovascular events
Curr Hypertens Rep 2013 Oct;15(5):514-21.PMID:23839110DOI:10.1007/s11906-013-0372-1.
How Chlorthalidone (CTDN) reduces risk for cardiovascular events (CVEs) can be considered in light of its ability to lower blood pressure (BP) and its non-BP related, pleiotropic effects. The mechanism by which CTDN lowers BP is unclear but may include alterations in whole body regulation and vasodilatory actions on vasculature, possibly mediated via its inhibitory effects on carbonic anhydrase. Additionally, CTDN has potentially beneficial, non-BP related, pleiotropic effects that include improvements in endothelial function, anti-platelet activity, and oxidative status. CTDN reduces pulse wave velocity, predictor of CVEs and a measure of central aortic stiffness associated with endothelial dysfunction. On the other hand, CTDN fosters hypokalemia, hyperglycemia, sympathetic discharge, and the renin-angiotensin-aldosterone system, but these potentially harmful effects do not appear to materially reduce CTDN's ability to prevent CVEs. Further, CTDN reduces and regresses left ventricular hypertrophy (LVH), an important BP-dependent predictor of CVEs. Consistent with this finding, CTDN was more effective than amlodipine in reducing congestive heart failure (CHF) in the Anti-hypertensive and Lipid-lowering Treatment to Prevent Heart Attach Trial (ALLHAT). In reducing CVEs, CTDN was superior to lisinopril in ALLHAT and superior to hydrochlorthiazide in observational cohort analyses and in network analyses of randomized trials. A statistical synthesis of randomized trials suggests that the reduction in cardiovascular risk from CTDN can be explained primarily on the basis of its ability to lower blood pressure rather than its influence upon non-BP related, pleiotropic effects.