Sematilide (hydrochloride)
(Synonyms: 司美利特盐酸盐一水合物,CK-1752 hydrochloride) 目录号 : GC45564
A class III antiarrhythmic agent
Cas No.:101526-62-9
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
Sematilide is a class III antiarrhythmic agent and an analog of sotalol .1 It prolongs electrically stimulated action potential duration (APD) and increases the effective refractory period (ERP) in isolated guinea pig left atria. Sematilide decreases spontaneous sinoatrial beating rates and induces ERP prolongation of the atrioventricular node in isolated perfused canine hearts.2 In situ, sematilide (1 mg/kg) increases ERP, prolonging cardiac refractoriness, in open-chest dog hearts. Sematilide (0.3-6 mg/kg) inhibits arrhythmias induced by programmed electrical stimulation (PES), but not coronary ligation and reperfusion, two-stage coronary ligation, adrenaline, or digitalis, in dogs.3 Formulations containing sematilide have been used in the treatment of arrhythmias.
References
1. Ishii, Y., Muraki, K., Kurihara, A., et al. Effects of sematilide, a novel class III antiarrhythmic agent, on action potential in guinea pig atrium. Jpn. J. Pharmacol. 68(2), 175-182 (1995).
2. Yamada, A., Motomura, S., and Hashimoto, K. Comparison of direct negative chronotropic and positive inotropic effects of sematilide to those of E-4031 and MS-551 and the reverse frequency-dependent prolongation of cardiac refractoriness of sematilide. J. Cardiovasc. Pharmacol. 27(1), 159-166 (1996).
3. Xue, Y.X., Eto, K., Akie, Y., et al. Antiarrhythmic and proarrhythmic effects of sematilide in canine ventricular arrhythmia models. Jpn. J. Pharmacol. 70(2), 129-138 (1996).
| Cas No. | 101526-62-9 | SDF | |
| 别名 | 司美利特盐酸盐一水合物,CK-1752 hydrochloride | ||
| Canonical SMILES | CS(NC1=CC=C(C(NCCN(CC)CC)=O)C=C1)(=O)=O.Cl | ||
| 分子式 | C14H23N3O3S.HCl | 分子量 | 349.9 |
| 溶解度 | DMF: 12 mg/ml,DMSO: 12 mg/ml,Ethanol: 3 mg/ml,PBS (pH 7.2): 5 mg/ml | 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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1 mg | 5 mg | 10 mg |
| 1 mM | 2.858 mL | 14.2898 mL | 28.5796 mL |
| 5 mM | 0.5716 mL | 2.858 mL | 5.7159 mL |
| 10 mM | 0.2858 mL | 1.429 mL | 2.858 mL |
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Antiarrhythmic and proarrhythmic effects of Sematilide in canine ventricular arrhythmia models
Jpn J Pharmacol 1996 Feb;70(2):129-38.PMID:8866750DOI:10.1254/jjp.70.129.
Using canine ventricular arrhythmia models induced by two-stage coronary ligation, digitalis, adrenaline, coronary ligation and reperfusion, and programmed electrical stimulation (PES), we examined the antiarrhythmic or proarrhythmic effects of Sematilide, N-[2(diethylamino)ethyl]-4-[(methylsulfonyl)amino]-benzamide hydrochloride. Sematilide in an intravenous (i.v.) dose range of 0.3 to 6.0 mg/kg prolonged the QTc interval, but had an antiarrhythmic effect only on the arrhythmias induced by PES (7 out of 10 dogs with old myocardial infarction). Sematilide was not effective on coronary ligation and reperfusion arrhythmia or the spontaneously occurring automaticity arrhythmias induced by two-stage coronary ligation, digitalis and adrenaline, respectively, and even aggravated digitalis- and adrenaline-induced arrhythmias. These results indicate that the class III agent Sematilide is similar to other new class III agents, such as d-sotalol, E-4031 and MS-551, in that it was not effective on the automaticity arrhythmias, but different from these new class III agents, in that Sematilide prevented only the induction of ventricular arrhythmias induced by PES and did not suppress the coronary ligation-reperfusion arrhythmias. The PES induced arrhythmias are thought to be induced exclusively by a reentrant mechanism, but the reperfusion arrhythmias may involve not only re-entry, but also automaticity, and we reported the effectiveness of MS-551, E-4031 and d-sotalol on the latter arrhythmia. Sematilide is different in that it even aggravated some automaticity arrhythmias.
Hemodynamic effects of intravenous Sematilide in patients with congestive heart failure: a class III antiarrhythmic agent without cardiodepressant effects
J Am Coll Cardiol 1995 Dec;26(7):1679-84.PMID:7594103DOI:10.1016/0735-1097(95)00376-2.
Objectives: This study sought to evaluate the hemodynamic effects of intravenous Sematilide hydrochloride, a selective class III antiarrhythmic agent, in patients with heart failure and left ventricular systolic dysfunction. Background: Class I antiarrhythmic agents, which primarily slow conduction, can depress ventricular function, particularly in patients with heart failure. In contrast, pure class III agents, which selectively prolong repolarization, do not adversely affect hemodynamic variables in animal models, but there are no data evaluating their hemodynamic effects in humans. Methods: In 39 patients with congestive heart failure and a left ventricular ejection fraction < 40%, hemodynamic and electrocardiographic measurements were obtained at baseline, after a loading dose and during a maintenance infusion of intravenous Sematilide using either a low (0.75 then 0.3 mg/min) or high dose (1.5 then 0.6 mg/min) regimen. The study had an 80% power to detect clinically meaningful differences in hemodynamic variables. Results: Both low (n = 20) and high (n = 19) dose Sematilide infusions produced dose-dependent increases in QT interval (5 +/- 8% [mean +/- SD] and 18 +/- 10%, respectively) and corrected QT interval (4 +/- 8% and 14 +/- 10%), and high dose Sematilide decreased heart rate by 7 +/- 10% (all p < 0.025 vs. baseline). Neither dose regimen had a statistically significant effect on any other hemodynamic variable, including mean arterial, right atrial, pulmonary artery and pulmonary capillary wedge pressures; cardiac index, stroke volume, systemic and pulmonary vascular resistances; and left ventricular stroke work index. Sematilide showed no adverse hemodynamic effects in patients with left ventricular ejection fraction < or = 25% or > 25% and in patients with cardiac index < 2 or > or = 2 liters/min per m2. Sustained polymorphic ventricular tachycardia (n = 1) and excessive QT prolongation (n = 4) were seen during the high dose. Conclusions: Sematilide, in the doses administered, prolonged repolarization but did not alter hemodynamic variables in patients with heart failure. These data suggest that class III antiarrhythmic agents, which selectively prolong repolarization, are not cardiodepressant but may be proarrhythmic in humans, especially at high doses.
Determination of Sematilide in plasma by high-performance liquid chromatography
J Pharm Sci 1991 Feb;80(2):157-9.PMID:2051320DOI:10.1002/jps.2600800214.
A method for the determination of Sematilide levels in human plasma is described. After the addition of an internal standard, plasma samples are adjusted to pH 8.5 and extracted with a solution of 7.5% isopropanol in methylene chloride. Separation from co-extracted matrix constituents is performed by reversed-phase HPLC followed by UV detection at 254 nm. The assay is linear in the concentration range 12-2400 ng/mL when 0.5-mL aliquots of plasma are extracted. Application of the method to the analysis of samples obtained from eight healthy volunteers given an oral dose of 100 mg of Sematilide hydrochloride is shown.
New aminocarboxamides with class III anti-arrhythmic activity
Arch Pharm (Weinheim) 1999 Jul;332(7):233-42.PMID:10450168DOI:10.1002/(sici)1521-4184(19997)332:7<233::aid-ardp233>3.0.co;2-6.
In the search for new anti-arrhythmic substances we discovered the class III activity of aminocarboxamides. These compounds show a prolongation of the effective refractory period. With some of them the prolongation is more pronounced after faster than after slower stimulation of the guinea pig papillary muscle. They should therefore be of interest in the treatment of cardiac arrhythmias after myocardial infarction and atrial fibrillation. The chemical synthesis, the structure-activity relationships of the new derivatives, their efficacy on the action potential duration (APD) and the effective refractory period (ERP) in vitro of isolated guinea pig papillary muscles are described and discussed in this paper. Since AWD 160-275 (13) and AWD 23-111 (14) exerted a pronounced APD90 and ERP prolongation at faster stimulation, they were selected for further electrophysiological characterization in vitro and in vivo. Anti-arrhythmic and pro-arrhythmic effects were determined in several animal models in comparison with dofetilide, Sematilide, and sotalol. 13 was found to be effective in preventing programmed electrical stimulation-induced arrhythmias in anaesthetized dogs and may therefore contribute to the therapy of dysrhythmias after myocardial infarction. The pro-arrhythmic effect of 14, investigated in a model of triggered activity in chloralose-anaesthetized rabbits under methoxamine infusion, is low in comparison with other class III anti-arrhythmics.
Synthesis and antifibrillatory activity of nibentan and its analogues
Eur J Med Chem 2000 Feb;35(2):205-15.PMID:10758282DOI:10.1016/s0223-5234(00)00116-1.
A series of 1,5-diaminopentane derivatives, structurally related to nibentan, was synthesized and tested for antifibrillatory activity. Improved modifications of some known chemical syntheses were proposed. (+/-)-N-[5-(Diethylamino)-1-(4-nitrophenyl)pentyl]-benzamide hydrochloride, (+/-)-N-[5-(diethylamino)-1-(4-nitrophenyl)pentyl]-4-nitrobenzamide hydrochloride and (+/-)-N-[5-(diethylamino)-1-(4-hydroxyphenyl)pentyl]-4-nitrobenzamide hydrochloride were more potent than nibentan and possessed a longer duration of action (up to 5 h in comparison with 60-90 min for nibentan). The antifibrillatory activity of (+/-)-N-[5-(diethylamino)-1-(4-methoxyphenyl)pentyl]-4-nitrobenzamide hydrochloride was comparable to that of nibentan but exceeded the potency of D-sotalol and Sematilide.