Nadolol
(Synonyms: 纳多洛尔; SQ-11725) 目录号 : GC39740
Nadolol (Corgard, Solgol, Anabet, SQ11725) is a non-selective beta-adrenergic antagonist with antihypertensive and antiarrhythmic activities.
Cas No.:42200-33-9
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
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- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Nadolol (Corgard, Solgol, Anabet, SQ11725) is a non-selective beta-adrenergic antagonist with antihypertensive and antiarrhythmic activities.
Nadolol is a new beta-adrenoceptor blocking agent without intrinsic sympathomimetic action and with an extremely long plasma half life[2]. Nadolol antagonizes isoproterenol-induced tachycardia and ouabain-induced arrhythmias in cats, antagonizes coronary artery ligation-induced ventricular fibrillation and suppresses ventricular ectopic activity during vagal stimulation in dogs[1].
In several experimental models (mongrel cats and mongrel dogs), nadolol is effective against cardiac arrhythmias. This anti-arrhythmic activity appears to be related to fi-adrenergic receptor blockade, an action that would antagonize the ability of catecholamines to induce arrhythmias by alteration of cardiac automaticity and conductivity. It is also effective in preventing ventricular fibrillation induced by ligation of the left anterior descending coronary artery. Nadolol has been demonstrated to have a half-life of 4 to 5 hr in animals. It does not block neuromuscular transmission at the junction of the vagus and heart. Furthermore, nadolol does not depress excitability of the heart, as demonstrated by the lack of effect on diastolic threshold in the intact heart of the dog[1]. It is rapidly absorbed from the gastrointestinal tract and remarkalely well-tolerated when given in extremely large doses[3].
[1] Dale B.Evans, et al. European Journal of Pharmacology. 1976, 35(1):17-27. [2] Frithz G. Curr Med Res Opin. 1978, 5(5):383-7. [3] Lee RJ, et al. Eur J Pharmacol. 1975, 33(2):371-82.
| Cas No. | 42200-33-9 | SDF | |
| 别名 | 纳多洛尔; SQ-11725 | ||
| Canonical SMILES | OC1CC2=C(C(OCC(O)CNC(C)(C)C)=CC=C2)CC1O | ||
| 分子式 | C17H27NO4 | 分子量 | 309.4 |
| 溶解度 | Methanol: 250 mg/mL (808.02 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 | 3.2321 mL | 16.1603 mL | 32.3206 mL |
| 5 mM | 0.6464 mL | 3.2321 mL | 6.4641 mL |
| 10 mM | 0.3232 mL | 1.616 mL | 3.2321 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 | ||||||||||
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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。
Noninferiority and Safety of Nadolol vs Propranolol in Infants With Infantile Hemangioma: A Randomized Clinical Trial
JAMA Pediatr 2022 Jan 1;176(1):34-41.PMID:34747977DOI:10.1001/jamapediatrics.2021.4565.
Importance: Propranolol for infantile hemangiomas (IH) has been shown to be effective and relatively safe. However, other less lipophilic β-blockers, such as Nadolol, may be preferable in individuals who experience propranolol unresponsiveness or adverse events. Objective: To document the noninferiority and safety of oral Nadolol compared with oral propranolol in infants with IH. Design, setting, and participants: This double-blind noninferiority prospective study with a noninferiority margin of 10% compared propranolol with Nadolol in infants aged 1 to 6 months with problematic IH. The study was conducted in 2 academic pediatric dermatology centers in Canada between 2016 and 2020. Infants aged 1 to 6 months with a hemangioma greater than 1.5 cm on the face or 3 cm or greater on another body part causing or with potential to cause functional impairment or cosmetic disfigurement. Interventions: Oral propranolol and Nadolol in escalating doses up to 2 mg/kg/d. Main outcomes and measure: Between-group differences comparing changes in the bulk (size and extent) and color of the IH at week 24 with baseline using a 100-mm visual analog scale. Results: The study included 71 patients. Of these, 36 were treated with propranolol. The mean (SD) age in this group was 3.1 (1.4) months, and 31 individuals (86%) were female. Thirty-five infants were treated with Nadolol. The mean (SD) age in this group was 3.2 (1.6) months, and 26 individuals (74%) were female. The difference in IH between groups by t test was 8.8 (95% CI, 2.7-14.9) for size and 17.1 (95% CI, 7.2-30.0) for color in favor of the Nadolol group, demonstrating that Nadolol was noninferior to propranolol. Similar differences were noted at 52 weeks: 6.0 (95% CI, 1.9-10.1) and 10.1 (95% CI, 2.9-17.4) for size and color improvement, respectively. For each doubling of time unit (week), the coefficient of involution was 2.4 (95% CI, 0.5-4.4) higher with Nadolol compared with propranolol. Safety data were similar between the 2 interventions. Conclusions and relevance: Oral Nadolol was noninferior to oral propranolol, indicating it may be an efficacious and safe alternative in cases of propranolol unresponsiveness or adverse events, or when faster involution is required. Trial registration: ClinicalTrials.gov Identifier: NCT02505971.
Clinical pharmacokinetics of Nadolol: A systematic review
J Clin Pharm Ther 2022 Oct;47(10):1506-1516.PMID:36040016DOI:10.1111/jcpt.13764.
What is known and objective: Nadolol is a non-selective beta-adrenergic antagonist that is used for the treatment of hypertension and angina. The primary route for its administration is oral. It is given once daily as it has a longer half-life (t½). The purpose of conducting this systematic review is to provide a comprehensive view of all the available pharmacokinetic (PK) data on Nadolol in humans. This review aimed to systematically collate and analyze publish data on the clinical PK of Nadolol in humans and this can be beneficial for the clinicians in dosage adjustments. Methods: Two electronic databases PubMed and Google Scholar were used for conducting a systematic literature search. All the relevant articles containing PK data of Nadolol in humans were retrieved. A total of 1275 articles were searched from both databases and after applying eligibility criteria finally, 22 articles were included for conducting the systematic review. Results and discussion: The area under the plasma concentration curve (AUC) and maximum plasma concentration (Cmax ) of Nadolol increased in a dose-dependent manner. The t½ of Nadolol was increased to double (18.2-68.6 h) in the patients with chronic kidney disease while the serum t½ became shorter (3.2-4.3 h) when administered to the children. The bioavailability of Nadolol was greatly reduced by the coadministration of green tea. Nadolol can be effectively removed by hemodialysis. It undergoes enterohepatic circulation thus activated charcoal decreased its bioavailability. What is new and conclusion: Since, there is no previous report of a systematic review on the PK of Nadolol, the current review encompasses all the relevant published articles on Nadolol in humans. The analysis and understanding of PK parameters (AUC, Cmax , and t½) of Nadolol may be helpful in the development and evaluation of PK models.
Propranolol versus Nadolol for treatment of pediatric subglottic hemangioma
Int J Pediatr Otorhinolaryngol 2021 May;144:110688.PMID:33773428DOI:10.1016/j.ijporl.2021.110688.
Purpose: The beta-blocker propranolol is the standard medical therapy for subglottic hemangioma (SGH), but side effects and incomplete response rates require close monitoring. Nadolol has been identified as a potential alternative but its use has not been examined for SGH. Methods: Single institution retrospective cohort study of pediatric SGH treated with propranolol or Nadolol. Results: Thirteen children (1 male, 12 female) with SGH were included: 6 were treated with propranolol (2.0-3.5 mg/kg/d) and 7 with Nadolol (2.0-4.0 mg/kg/d). The most common presenting symptom was stridor (85%) and mean (SD) symptom duration prior to diagnosis was 4.6 (3.8) weeks. Cutaneous vascular lesions were present in 54%. There were 7 right-sided, 5 left-sided and 1 bilateral SGH. The mean (SD) percentage of airway obstruction was 60.6% (27.4). The response rate was 100% (6/6) for propranolol and 85.7% (6/7) for Nadolol (p = 0.36). Mean (SD) time to symptomatic improvement was 2.6 (2.2) days with no difference across groups (p = 0.71). There was no hypotension, hypoglycemia, weight loss, or sleep disturbances in either group. One patient in the propranolol group experienced vomiting. Two patients in the Nadolol group required dosage reduction due to asymptomatic bradycardia. The mean (SD) duration of admission was 14.4 (12.6) days and duration of treatment was 13.8 (11.2) days with no difference across groups (p = 0.23; p = 0.31, respectively). All patients had treatment initiated as inpatients and completed as outpatients. Conclusion: Children with SGH treated with propranolol or Nadolol had similar response rates and side effect profiles.
Dose response to Nadolol in congenital long QT syndrome
Heart Rhythm 2021 Aug;18(8):1377-1383.PMID:33905813DOI:10.1016/j.hrthm.2021.04.021.
Background: Beta-blocker therapy is the cornerstone of treatment for patients with long QT syndrome (LQTS). Few details on the dose to be used are available. As the response is variable between patients, we systematically evaluated the effect of treatment by performing an exercise test. Objective: The purpose of this study was to explore dose response to Nadolol on exercise test in LQTS patients in order to propose a more personalized therapeutic approach. Methods: LQTS patients followed at the Reference Centre for Hereditary Arrhythmic Diseases of Nantes with at least 1 exercise test under Nadolol were included retrospectively between 1993 and 2017. All patients underwent gradual cycle exercise tests. Doses adjusted to weight and response to treatment were recorded and evaluated by the percentage of age-predicted maximum heart rate reached on exercise test. Results: Ninety-five patients were included in the study, and 337 stress tests under Nadolol were analyzed. No correlation existed between dose and percentage of age-predicted maximum heart rate on exercise tests. Twenty-one patients were overresponders, mostly LQTS1, and 20 were underresponders, mainly LQTS2 (P = .0229). Forty-two patients had at least 3 stress tests under Nadolol. We found a negative correlation between dose change and percentage of age-predicted maximum heart rate change (P <.0001). We then proposed a table to adapt dose according to exercise test response. Conclusion: Our study demonstrated a major variability of dose response to Nadolol in patients with LQTS, thus underlining the need for a tailored dosage for each patient. Intraindividual analysis showed a relatively constant dose-response relationship, allowing guided dose adaptation after the first exercise test.
Carvedilol versus traditional, non-selective beta-blockers for adults with cirrhosis and gastroesophageal varices
Cochrane Database Syst Rev 2018 Oct 29;10(10):CD011510.PMID:30372514DOI:10.1002/14651858.CD011510.pub2.
Background: Non-selective beta-blockers are recommended for the prevention of bleeding in people with cirrhosis, portal hypertension and gastroesophageal varices. Carvedilol is a non-selective beta-blocker with additional intrinsic alpha1-blocking effects, which may be superior to traditional, non-selective beta-blockers in reducing portal pressure and, therefore, in reducing the risk of upper gastrointestinal bleeding. Objectives: To assess the beneficial and harmful effects of carvedilol compared with traditional, non-selective beta-blockers for adults with cirrhosis and gastroesophageal varices. Search methods: We combined searches in the Cochrane Hepato-Biliary's Controlled Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, LILACS, and Science Citation Index with manual searches. The last search update was 08 May 2018. Selection criteria: We included randomised clinical trials comparing carvedilol versus traditional, non-selective beta-blockers, irrespective of publication status, blinding, or language. We included trials evaluating both primary and secondary prevention of upper gastrointestinal bleeding in adults with cirrhosis and verified gastroesophageal varices. Data collection and analysis: Three review authors (AZ, RJ and LH), independently extracted data. The primary outcome measures were mortality, upper gastrointestinal bleeding and serious adverse events. We undertook meta-analyses and presented results using risk ratios (RR) or mean differences (MD), both with 95% confidence intervals (CIs), and I2 values as a marker of heterogeneity. We assessed bias control using the Cochrane Hepato-Biliary domains and the quality of the evidence with GRADE. Main results: Eleven trials fulfilled our inclusion criteria. One trial did not report clinical outcomes. We included the remaining 10 randomised clinical trials, involving 810 participants with cirrhosis and oesophageal varices, in our analyses. The intervention comparisons were carvedilol versus propranolol (nine trials), or Nadolol (one trial). Six trials were of short duration (mean 6 (range 1 to 12) weeks), while four were of longer duration (13.5 (6 to 30) months). Three trials evaluated primary prevention; three evaluated secondary prevention; while four evaluated both primary and secondary prevention. We classified all trials as at 'high risk of bias'. We gathered mortality data from seven trials involving 507 participants; no events occurred in four of these. Sixteen of 254 participants receiving carvedilol and 19 of 253 participants receiving propranolol or Nadolol died (RR 0.86, 95% CI 0.48 to 1.53; I2 = 0%, low-quality evidence). There appeared to be no differences between carvedilol versus traditional, non-selective beta-blockers and the risks of upper gastrointestinal bleeding (RR 0.77, 95% CI 0.43 to 1.37; 810 participants; 10 trials; I2 = 45%, very low-quality evidence) and serious adverse events (RR 0.97, 95% CI 0.67 to 1.42; 810 participants; 10 trials; I2 = 14%, low-quality evidence). Significantly more deaths, episodes of upper gastrointestinal bleeding and serious adverse events occurred in the long-term trials but there was not enough information to determine whether there were differences between carvedilol and traditional, non-selective beta-blockers, by trial duration. There was also insufficient information to detect differences in the effects of these interventions in trials evaluating primary or secondary prevention. There appeared to be no differences in the risk of non-serious adverse events between carvedilol versus its comparators (RR 0.55, 95% CI 0.23 to 1.29; 596 participants; 6 trials; I2 = 88%; very low-quality evidence). Use of carvedilol was associated with a greater reduction in hepatic venous pressure gradient than traditional, non-selective beta-blockers both in absolute (MD -1.75 mmHg, 95% CI -2.60 to -0.89; 368 participants; 6 trials; I2 = 0%; low-quality evidence) and percentage terms (MD -8.02%, 95% CI -11.49% to -4.55%; 368 participants; 6 trials; I2 = 0%; low-quality evidence). However, we did not observe a concomitant reduction in the number of participants who failed to achieve a sufficient haemodynamic response (RR 0.76, 95% CI 0.57 to 1.02; 368 participants; 6 trials; I2 = 42%; very low-quality evidence) or in clinical outcomes. Authors' conclusions: We found no clear beneficial or harmful effects of carvedilol versus traditional, non-selective beta-blockers on mortality, upper gastrointestinal bleeding, serious or non-serious adverse events despite the fact that carvedilol was more effective at reducing the hepatic venous pressure gradient. However, the evidence was of low or very low quality, and hence the findings are uncertain. Additional evidence is required from adequately powered, long-term, double-blind, randomised clinical trials, which evaluate both clinical and haemodynamic outcomes.