Almokalant (H 234/09)
(Synonyms: 阿莫兰特,H 234?/09) 目录号 : GC32673
Almokalant (H 234/09) 是一种 III 类抗心律失常药物，作为钾通道阻滞剂，可抑制时间依赖性延迟整流器 K+ 电流的特定成分 (Ikr)。
Cas No.:123955-10-2
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
Almokalant is a class III antiarrhythmic drug, acts as a potassium channel blocker, and inhibits a specific component (Ikr) of the time-dependent delayed rectifier K+ current.
Almokalant is a class III antiarrhythmic drug, acts as a potassium channel blocker, and inhibits a specific component (Ikr) of the time-dependent delayed rectifier K+ current[1].
Almokalant (125 μmol/kg, p.o.) induces cardiovascular defects, orofacial clefts, and tail defects in pregnant rats, after administration on Day 11. Almokalant also causes in pregnant rats[1].
[1]. Wellfelt K, et al. Teratogenicity of the class III antiarrhythmic drug almokalant. Role of hypoxia and reactive oxygen species. Reprod Toxicol. 1999 Mar-Apr;13(2):93-101.
| Cas No. | 123955-10-2 | SDF | |
| 别名 | 阿莫兰特,H 234?/09 | ||
| Canonical SMILES | CCCS(CCCN(CC)CC(O)COC1=CC=C(C#N)C=C1)=O | ||
| 分子式 | C18H28N2O3S | 分子量 | 352.49 |
| 溶解度 | Soluble in DMSO | 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 | 2.837 mL | 14.1848 mL | 28.3696 mL |
| 5 mM | 0.5674 mL | 2.837 mL | 5.6739 mL |
| 10 mM | 0.2837 mL | 1.4185 mL | 2.837 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。
Electrophysiologic and hemodynamic effects of H 234/09 (Almokalant), quinidine, and (+)-sotalol in the anesthetized dog
J Cardiovasc Pharmacol 1992 Sep;20(3):458-65.PMID:1279293DOI:10.1097/00005344-199209000-00018.
The electrophysiologic and hemodynamic effects of H 234/09 (Almokalant), a novel class II antiarrhythmic agent, were studied in the anesthetized dog. H 234/09 (1.0 mumol/kg i.v.) significantly prolonged the atrial and ventricular effective refractory periods, the ventricular monophasic action potential duration, and the paced QT interval. At this dose, atrial, ventricular, and atrioventricular conduction was not affected, aortic blood pressure was not changed, and contractile force was transiently increased. The effects on cardiac repolarization and refractoriness induced by H 234/09 were both larger and more long lasting than the effects observed after quinidine (11.8 mumol/kg) and (+)-sotalol (9.7 mumol/kg). However, both quinidine and (+)-sotalol significantly reduced the aortic blood pressure and (+)-sotalol also decreased cardiac contractility. The effect of H 234/09 on atrial refractoriness was very little influenced by the paced heart rate and was twice as large as the corresponding effect in the ventricle. In conclusion, H 234/09 has electrophysiological properties suggestive of a class III antiarrhythmic. H 234/09 may have a favorable therapeutic profile compared to both quinidine and (+)-sotalol, especially for the treatment of atrial arrhythmias.
Electrophysiological and inotropic effects of H 234/09 (Almokalant) in vitro: a comparison with two other novel IK blocking drugs, UK-68,798 (dofetilide) and E-4031
Cardiovasc Res 1993 May;27(5):861-7.PMID:8348585DOI:10.1093/cvr/27.5.861.
Objective: The aim was to compare the electrophysiological and inotropic effects of the novel class III agents H 234/09, UK-68,798, and E-4031 in vitro. Methods: The electrophysiological effects were investigated by recording transmembrane action potentials in the isolated ventricular muscle and Purkinje fibres of the rabbit; effects on force (adjusted to the maximum isoprenaline response) and refractoriness were investigated in the isolated cat papillary muscle. Results: It was shown that all the drugs induced a concentration dependent prolongation of the action potential duration, which was much more pronounced in the Purkinje fibres than in the ventricular muscle. However, when compared at concentrations giving a 15% increase of the action potential duration in ventricular muscle, H 234/09 was significantly less effective in the Purkinje fibres than the other two drugs. In the cat papillary muscle all drugs induced an increase in force development. This increase tended to parallel the increase in effective refractory period. However, at prolongations of effective refractory period of more than approximately 50% the increase in developed force levelled off. Conclusions: All the class III agents investigated showed a positive inotropic effect, which may be of advantage when compared to conventional class I antiarrhythmic agents, which have cardiodepressant actions. Compared to UK-68,798 and E-4031, H 234/09 showed a less unfavourable profile in terms of dispersion of repolarisation, which theoretically may reduce the risk of arrhythmias associated with delayed repolarisation. However, this less unfavourable profile must, like the positive inotropic effect, ultimately be investigated in clinical trials.
Prolonged action potential duration and positive inotropy induced by the novel class III antiarrhythmic agent H 234/09 (Almokalant) in isolated human ventricular muscle
J Cardiovasc Pharmacol 1991 Dec;18(6):882-7.PMID:1725902DOI:10.1097/00005344-199112000-00015.
The electromechanical properties of H 234/09 (Almokalant), a novel class III antiarrhythmic agent, was examined in isolated human ventricular muscle strips excised from patients undergoing mitral valve replacement. Using transmembrane microelectrode recording techniques, we demonstrated that H 234/09 markedly prolonged the action potential duration (APD) without affecting the maximal rate of depolarization or action potential amplitude. At 75 and 90% repolarization APD was prolonged to a similar extent, whereas the lengthening at 50% repolarization was somewhat less marked. In isometrically contracting muscle strips, H 234/09 increased peak developed force and its maximal rate of rise (dF/dt) and fall (-dF/dt) in a concentration-dependent manner, whereas time to peak developed force was unaltered. We conclude from these studies that H 234/09 is a class III agent in human ventricular muscle and that the class III effect is linked with a positive inotropic response.
Lidocaine and nisoldipine attenuate almokalant-induced dispersion of repolarization and early afterdepolarizations in vitro
J Cardiovasc Electrophysiol 1996 Nov;7(11):1074-81.PMID:8930739DOI:10.1111/j.1540-8167.1996.tb00483.x.
Introduction: Treatment with Class III antiarrhythmic agents may lead to increased dispersion of repolarization and early afterdepolarizations (EADs), which are both likely substrates for torsades de pointes. Recent studies in vivo have shown that the prevalence of proarrhythmias induced by Class III agents may be reduced by Na(+)- or Ca(2+)-blocking agents. In the present study, tentative mechanisms for this protective effect were investigated in vitro. Methods and results: Transmembrane action potentials were recorded simultaneously from rabbit isolated ventricular muscle (VM) and Purkinje fibers (PF). At a basic cycle length (BCL) of 500 msec, the Class III agent Almokalant (0.1 microM) increased the dispersion by prolonging the action potential duration (APD) significantly more in the PF (33% +/- 4.2%, n = 18) than in the VM (17% +/- 5.9%, n = 18, P < 0.05). In six of the preparations, addition of 1, 5, and 25 microM lidocaine reduced the almokalant-induced prolongation in a concentration-dependent manner mainly in the PF, thereby decreasing the dispersion. At 5 microM lidocaine, the remaining prolongation was 7% +/- 12.2% (P < 0.05 vs time controls) in the PF and 14% +/- 6.4% in the VM, respectively. In six other preparations, the addition of 0.01, 0.05, and 0.25 microM nisoldipine did not reduce the almokalant-induced prolongation in the PF and VM, but attenuated the spike-and-dome appearance of the action potential in the PF. In separate experiments performed at a BCL of 1000 msec, EADs developed in 2 of 6 and 5 of 6 PF during superfusion with Almokalant (0.3 and 1 microM, respectively) at an APD of 828 +/- 41.4 msec. In six separate preparations pretreated with lidocaine (5 microM), the almokalant-induced prolongation in the PF was less pronounced and EADs were not observed. Pretreatment with nisoldipine (0.05 microM) did not influence the response to Almokalant, and in 4 of 6 preparations the APD exceeded 1000 msec. Despite this extensive prolongation, EADs did not appear. Conclusion: At concentrations that did not affect the APD in the VM but reduced the APD in the PF, lidocaine suppressed almokalant-induced dispersion and the development of EADs. Nisoldipine, on the other hand, inhibited almokalant-induced EADs directly. Hence, the primary APD-prolonging effect of a Class III agent may be preserved, but the risk of proarrhythmias reduced, during concomitant treatment with low concentrations of a Na(+)- or Ca(2+)-blocking agent.
Almokalant glucuronidation in human liver and kidney microsomes: evidence for the involvement of UGT1A9 and 2B7
Xenobiotica 2003 Nov;33(11):1073-83.PMID:14660172DOI:10.1080/00498250310001609129.
1. Almokalant, a class III antiarrythmic drug, is metabolized to form isomeric glucuronides identified in human urine. Synthesis of the total glucuronide was studied in human liver and kidney microsomes. Recombinant UDP-glucuronosyltransferases (UGTs) were screened for activity and kinetic analysis was performed to identify the isoform(s) responsible for the formation of Almokalant glucuronide in man. 2. From a panel of recombinant isoforms used, both UGT1A9 and 2B7 catalysed the glucuronidation of Almokalant. The Km values in both instances were similar with 1.06 mM for the 1A9 and 0.97 mM for the 2B7. Vmax for 1A9 was fourfold higher than that measured for UGT2B7, 92 compared with 21 pmol min(-1) mg(-1), respectively, but UGT1A9 was expressed at approximately twofold higher level than the UGT2B7 in the recombinant cell lines. Therefore, the contribution of UGT2B7 to Almokalant glucuronidation could be as significant as that of UGT1A9 in man. 3. Liver and kidney microsomes displayed similar Km values to the cloned expressed UGTs, with the liver and kidney microsomes at 1.68 and 1.06 mM almost identical to the 1A9. 4. The results suggest a significant role for UGT1A9 and 2B7 in the catalysis of Almokalant glucuronidation.