N-Acetylprocainamide (Acecainide)
(Synonyms: N-乙酰普鲁卡因胺; Acecainide; NAPA) 目录号 : GC34027
N-Acetylprocainamide (Accecainide) 是一种 III 类抗心律失常药，可阻断 K+ 通道。
Cas No.:32795-44-1
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
N-Acetylprocainamide is a class III antiarrhythmic, which blocks K+ channels.
N-Acetylprocainamide is a K+ blocker. N-Acetylprocainamide decreases the tensions induced by K+ and methacholine. The pIC50 values for N-acetylprocainamide against the contractions induced by 0.3 and 1 μM methacholine are 2.80 ± 0.03 and 2.65 ± 0.02, respectively. And such a relaxant effect of N-Acetylprocainamide is inhibited by K+ channel blockers[1]. N-Acetylprocainamide shows no effect on Na+ absorption or Cl- secretion[2].
[1]. Nakahara T, et al. Role of K+ channels in N-acetylprocainamide-induced relaxation of bovine tracheal smooth muscle. Eur J Pharmacol. 2001 Mar 9;415(1):73-8. [2]. Plass H, et al. Class I antiarrhythmics inhibit Na+ absorption and Cl- secretion in rabbit descending colon epithelium. Naunyn Schmiedebergs Arch Pharmacol. 2005 Jun;371(6):492-9.
| Cas No. | 32795-44-1 | SDF | |
| 别名 | N-乙酰普鲁卡因胺; Acecainide; NAPA | ||
| Canonical SMILES | O=C(NCCN(CC)CC)C1=CC=C(NC(C)=O)C=C1 | ||
| 分子式 | C15H23N3O2 | 分子量 | 277.36 |
| 溶解度 | DMSO : ≥ 150 mg/mL (540.81 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 | 3.6054 mL | 18.0271 mL | 36.0542 mL |
| 5 mM | 0.7211 mL | 3.6054 mL | 7.2108 mL |
| 10 mM | 0.3605 mL | 1.8027 mL | 3.6054 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。
Acecainide (N-Acetylprocainamide). A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in cardiac arrhythmias
Drugs 1990 May;39(5):720-40.PMID:1693889DOI:10.2165/00003495-199039050-00007.
Acecainide (N-Acetylprocainamide), the N-acetylated metabolite of procainamide, is a Class III antiarrhythmic agent. It can be given either intravenously or orally, and is eliminated primarily by renal excretion. In a small number of noncomparative and placebo-controlled short term therapeutic trials Acecainide markedly reduced premature ventricular beats and prevented induction of ventricular tachycardia in more than 70% of patients following intravenous administration and in about 50% after oral administration. Acecainide was effective in about one-quarter of patients refractory to other antiarrhythmic drugs. Interpretation of its effectiveness following long term oral therapy is complicated by the limited number of patients, and patients discontinuing due to adverse effects or lack of efficacy. However, about 40% of the small number treated for extended periods were controlled for periods of 6 months to 3 to 4 years. Comparative studies with other antiarrhythmic drugs have not been undertaken apart from a small study in atrial flutter where Acecainide was better than quinidine plus digoxin. Thus, although further clinical experience is required before the relative place of Acecainide in therapy can be determined, the drug nevertheless appears to offer advantages over procainamide, particularly with respect to the reduced formation of antinuclear antibodies.
Clinical pharmacokinetics of N-Acetylprocainamide
Clin Pharmacokinet 1982 May-Jun;7(3):206-20.PMID:6178545DOI:10.2165/00003088-198207030-00002.
Since N-Acetylprocainamide was identified in the urine of patients receiving procainamide, this compound has been studied both as a metabolite of procainamide and as a separate antiarrhythmic agent. N-Acetylprocainamide absorption following oral administration is more than 8-% complete. 59 to 89% of N-Acetylprocainamide is excreted unchanged in the urine in subjects with normal renal function. Deacetylation of N-Acetylprocainamide to procainamide is a minor route of N-Acetylprocainamide elimination. The half-life of N-Acetylprocainamide in patients with normal renal function has been reported to vary between 4.3 and 15.1 hours. Total body clearance (mean +/- SD) of N-Acetylprocainamide in patients with normal renal function has been reported to range from 2.08 +/- 0.36 ml/min/kg to 3.28 +/- 0.52 ml/min/kg. There is a linear relationship between N-Acetylprocainamide clearance and creatinine clearance. The half-life of N-Acetylprocainamide in functionally anephric patients may be as long as 42 hours; however, it can be effectively cleared from plasma by haemodialysis. N-Acetylprocainamide is 10% protein-bound. There is an age-related decline in N-Acetylprocainamide clearance, mostly due to the decrease in creatinine clearance that occurs with ageing. In the neonate, the half-life of acetylprocainamide is prolonged. Several therapeutic trials carried out to assess the effectiveness of N-Acetylprocainamide in suppressing chronic ventricular premature beats have now been reported. If there is a therapeutic response to N-Acetylprocainamide it will probably occur at a plasma concentration between 15 and 25 micrograms/ml. A high degree of overlap has been reported between the concentration range associated with arrhythmic suppression and the range of concentrations where intolerable side effects begin to occur. No severe cardiac toxicity has been reported with oral therapy despite plasma concentrations as high as 40 micrograms/ml. However, hypotension has been reported in association with a rapid intravenous bolus of N-Acetylprocainamide. A maximum intravenous infusion rate of 50 mg/min has been recommended. N-Acetylprocainamide in patients receiving procainamide; however, N-Acetylprocainamide concentrations remain below the therapeutic range in patients with normal renal function. In patients with renal failure receiving procainamide, N-Acetylprocainamide concentrations rise dramatically. The dose of N-Acetylprocainamide must be adjusted in patients with renal insufficiency, and it should be used more cautiously in the very old and very young. N-Acetylprocainamide plasma concentration monitoring would be valuable clinically in patients with renal insufficiency receiving either N-Acetylprocainamide or procainamide, and in the very young and the aged.
Antiarrhythmic efficacy, pharmacokinetics and safety of N-Acetylprocainamide in human subjects: comparison with procainamide
Am J Cardiol 1980 Sep;46(3):463-8.PMID:6158263DOI:10.1016/0002-9149(80)90016-8.
The antiarrhythmic efficacy and pharmacokinetics of N-Acetylprocainamide (NAPA), the major metabolite of procainamide, were investigated in 23 patients with chronic, high frequency ventricular ectopic depolarizations. An extensive trial design incorporated the approaches of (1) generation of dose-response relations, (2) randomized crossover, and (3) prolonged electrocardiographic monitoring. Seven patients with reproducible suppression of arrhythmias (70 percent or greater reduction in frequency) were thus identified. The mean plasma concentration of Acecainide associated with efficacy was 14.3 micrograms/ml (range 9.4 to 19.5) and with side effects (primarily gastrointestinal) was 22.5 micrograms/ml (10.6 to 37.9). The antiarrhythmic response to procainamide did not predict response to Acecainide; this finding implies that estimates of the antiarrhythmic contribution of Acecainide concentrations achieved during long-term procainamide therapy are unlikely to be meaningful in a given person. The mean half-life of elimination after a single 500 mg dose of Acecainide was 7.5 hours; this had prolonged significantly (p < 0.05) to 10.3 hours after higher dosages. No variable examined (including acetylator phenotype) was found to be a predictor of responsiveness to Acecainide. Outpatient therapy (2 to 20 months) was not associated with the development of antinculear antibodies or the lupus syndrome; one patient's procainamide-induced arthritis resolved during therapy. Acecainide, unlike procainamide, is an agent whose pharmacokinetics allow long-term therapy on a practical schedule. It is effective in a subset of patients with ventricular arrhythmias yet appears much less likely to induce the lupus syndrome seen with the parent compound.
Pharmacokinetics of N-Acetylprocainamide
Angiology 1986 Dec;37(12 Pt 2):959-67.PMID:2433970doi
Shortly after Dreyfus and his colleagues demonstrated that procainamide was metabolized by acetylation to N-Acetylprocainamide (NAPA), Drayer, Reidenberg and Sevy reported that NAPA had antiarrhythmic activity in an animal model. We confirmed these findings and found that plasma levels of NAPA were high enough to warrant consideration in managing patients requiring procainamide therapy. However, the actual impetus for developing NAPA as an antiarrhythmic drug in its own right was provided by the initial studies of NAPA pharmacokinetics in normal subjects. In these studies, we showed that NAPA has an elimination-phase half-life that is more than twice as long as procainamide and suggested that patient compliance and arrhythmia suppression might be improved if NAPA were used to circumvent the inconvenience of the frequent dosing schedule that has been recommended for procainamide. From the standpoint of managing individual patients with NAPA, the pharmacokinetics of this drug continue to provide the scientific basis for designing dose regimens that will have maximal antiarrhythmic efficacy and minimal toxicity. This review summarizes the salient features of NAPA pharmacokinetics and outlines an approach for individualizing therapy with this drug.
Kinetics of N-Acetylprocainamide deacetylation
Clin Pharmacol Ther 1980 Nov;28(5):659-66.PMID:6160014DOI:10.1038/clpt.1980.218.
The kinetics of N-Acetylprocainamide (NAPA) deacetylation to procainamide (PA) were determined in a normal subject using NAPA-13C, labeled in the acetyl group. The deacetylation clearance of NAPA (ClD) was found to be 6.5 ml/min whereas total NAPA elimination clearance was 231 ml/min, so that 2.8% of the administered NAPA-13C was metabolized by deacetylation. This estimated of ClD was shown to be representative of the rate of NAPA deacetylation in four patients on long-term NAPA therapy. Steady-state [PA]/[NAPA] ratios averaged 0.024, but would be expected to rise to 0.057 if functionally anephric patients were treated with NAPA. Despite reports that patients with the PA-induced systemic lupus erythematosus-like reaction have had symptomatic and immunologic remission when switched to NAPA, the demonstration that NAPA is deacetylated to PA indicates that the apparently greater immunologic safety of NAPA may be relative rather than absolute.