Ajmaline (Cardiorythmine)
(Synonyms: 阿义吗啉) 目录号 : GC34018
An alkaloid
Cas No.:4360-12-7
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
Ajmaline is an alkaloid that has been found in R. serpentina and has ion channel inhibitory and antiarrhythmic activities.1,2,3,4,5 It inhibits the human-ether-a-go-go (hERG) potassium channel, also known as Kv11.1, and the voltage-gated potassium channel subtypes Kv1.5 and Kv4.3 with IC50 values of 42.3, 293, and 186 ?M, respectively, in Xenopus oocytes expressing the channels.2,3 Ajmaline (1 ?g/ml) increases the action potential duration in isolated dog atrium and ventricle.4 It increases the functional refractory duration in the atrium, ventricle, and atrioventricular conduction system in anesthetized dogs when administered intravenously at a dose of 1 mg/kg.4 Ajmaline (2 mg/kg, i.v.) reduces the number of premature ventricular complexes and decreases the duration of ventricular tachycardia and ventricular fibrillation in coronary artery-ligated anesthetized rats.5
1.Srivastava, A., Tripathi, A.K., Pandey, R., et al.Quantitative determination of reserpine, ajmaline, and ajmalicine in Rauvolfia serpentina by reversed-phase high-performance liquid chromatographyJ. Chromatogr. Sci.44(9)557-560(2006) 2.Kiesecker, C., Zitron, E., Lück, S., et al.Class Ia anti-arrhythmic drug ajmaline blocks HERG potassium channels: Mode of actionNaunyn-Schmiedebergs Arch. Pharmacol.370(6)423-435(2004) 3.Fischer, F., Vonderlin, N., Zitron, E., et al.Inhibition of cardiac Kv1.5 and Kv4.3 potassium channels by the class Ia anti-arrhythmic ajmaline: Mode of actionNaunyn-Schmiedebergs Arch. Pharmacol.386(11)991-999(2013) 4.Bojorges, R., Pastelin, G., Sanchez-Perez, S., et al.The effects of ajmaline in experimental and clinical arrhythmias and their relation to some electrophysiological parameters of the heartJ. Pharmacol. Exp. Ther.193(1)182-193(1975) 5.Hashimoto, Y., Hori, R., Okumura, K., et al.Pharmacokinetics and antiarrhythmic activity of ajmaline in rats subjected to coronary artery occlusionBr. J. Pharmacol.88(1)71-77(1986)
| Cas No. | 4360-12-7 | SDF | |
| 别名 | 阿义吗啉 | ||
| Canonical SMILES | CN1C2=CC=CC=C2[C@@]34[C@]1([H])[C@@](CC5[C@H](CC)[C@H]6O)([H])N6[C@]([H])(C5[C@H]4O)C3 | ||
| 分子式 | C20H26N2O2 | 分子量 | 326.43 |
| 溶解度 | DMSO : ≥ 66 mg/mL (202.19 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 | 3.0634 mL | 15.3172 mL | 30.6344 mL |
| 5 mM | 0.6127 mL | 3.0634 mL | 6.1269 mL |
| 10 mM | 0.3063 mL | 1.5317 mL | 3.0634 mL |
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| 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 |
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| % 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，
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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。
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Ajmaline Testing and the Brugada Syndrome
Am J Cardiol 2020 Nov 15;135:91-98.PMID:32861732DOI:10.1016/j.amjcard.2020.08.024.
Brugada syndrome (BrS) diagnosis requires the presence of a typical type 1 ECG pattern. Owing to the spontaneous ECG variability, the real BrS prevalence in the general population remains unclear. The aim of the present study was to evaluate the prevalence of positive Ajmaline challenge for BrS in a cohort of consecutive patients who underwent electrophysiological evaluation for different clinical reasons. All consecutive patients from 2008 to 2019 who underwent Ajmaline testing were prospectively included. A total of 2,456 patients underwent Ajmaline testing, 742 (30.2%) in the context of familial screening for BrS. In non-familial screening group (1,714) Ajmaline testing resulted positive in 186 (10.9%). Indications for Ajmaline testing were: suspicious BrS ECG in 23 cases (12.4%), palpitations in 27 (14.5%), syncope in 71 (38.2%), presyncope in 7 (3.8%), family history of sudden cardiac death in 18 (9.7%), documented ventricular arrhythmias in 12 (6.5%), unexplained cardiac arrest in 4 (2.2%), atrial fibrillation in 16 (8.5%), brady-arrhythmias in 1 (0.5%), and cerebrovascular accidents in 7 (3.7%). Compared with the overall population, Ajmaline testing positive patients were younger (42.8 ± 15.5 vs 48.9 ± 20.4; p <0.001) and more frequently male (65.1% vs 56.3%; p = 0.023). Implantable cardioverter defibrillator was implanted in 84 patients (45.2%). During a median follow-up of 42.4 months, 12 appropriate shocks and 13 implantable cardioverter defibrillator related complications were reported. In conclusion, the BrS was diagnosed in an unexpected high proportion of patients that underwent Ajmaline testing for a variety of cardiovascular symptoms. This can lead to an adequate counseling and clinical management in BrS patients.
Metabolic disposition of Ajmaline
Eur J Drug Metab Pharmacokinet 1989 Oct-Dec;14(4):309-16.PMID:2633926DOI:10.1007/BF03190117.
Urine was collected from six patients receiving a continuous infusion of 20 mg/h Ajmaline. Pooled urine was extracted with and without enzymatic conjugate cleavage or hydrolysis with concentrated hydrochloric acid. The extracts were analyzed by gas chromatography/mass spectrometry. Ajmaline and its metabolites in urine were identified in the form of their acetylated derivatives. Twenty two different acetylated derivatives of Ajmaline and its metabolites could be detected. Three of these derivatives were artifacts generated by acetylation and/or thermal decomposition. The major metabolic pathways were mono- and di-hydroxylation of the benzene ring with subsequent O-methylation, reduction of the C-21, oxidation of the C-17 and C-21-hydroxyl function, N-oxidation, and a combination of these metabolic steps. Ajmaline and its metabolites were mainly excreted in the form of their conjugates. Furthermore, the interference of sparteine, debrisoquine, quinidine, and nifedipine with Ajmaline metabolism was studied with semiquantitative thin-layer chromatography. Ajmaline metabolism was inhibited by co-administration of sparteine or quinidine, but not by debrisoquine or nifedipine. Sparteine most likely competed with Ajmaline metabolism. Quinidine probably bound competitively to ajmaline-metabolizing enzymes without being metabolized itself. Additionally, the metabolic ratio of hydroxyajmaline/Ajmaline in urine was determined in 9 extensive metabolizers and one poor metabolizer of dextromethorphan. The poor metabolizer had a significantly reduced metabolic ratio of hydroxyajmaline/Ajmaline, which indicates that Ajmaline metabolism probably co-segregates with polymorphic sparteine/debrisoquine/dextromethorphan metabolism.
Sarpagine and Related Alkaloids
Alkaloids Chem Biol 2016;76:63-169.PMID:26827883DOI:10.1016/bs.alkal.2015.08.002.
The sarpagine-related macroline and Ajmaline alkaloids share a common biosynthetic origin, and bear important structural similarities, as expected. These indole alkaloids are widely dispersed in 25 plant genera, principally in the family Apocynaceae. Very diverse and interesting biological properties have been reported for this group of natural products. Isolation of new sarpagine-related alkaloids and the asymmetric synthesis of these structurally complex molecules are of paramount importance to the synthetic and medicinal chemists. A total of 115 newly isolated sarpagine-related macroline and Ajmaline alkaloids, along with their physicochemical properties have been included in this chapter. A general and efficient strategy for the synthesis of these monomeric alkaloids, as well as bisindoles, has been presented, which involves application of the asymmetric Pictet-Spengler reaction (>98% ee) as a key step because of the ease of scale up of the tetracyclic template. Also included in this chapter are the syntheses of the sarpagine-related alkaloids, published since 2000.
Cardiovascular effects of Ajmaline
Am Heart J 1976 Oct;92(4):487-96.PMID:961588DOI:10.1016/s0002-8703(76)80049-x.
Ajmaline, a rauwolfia derivative, has been found to possess potent antiarrhythmic effects. The present study has been designed to define the cardiovascular effects of this drug. Hemodynamic studies performed in anesthetized and conscious dogs demonstrated no significant changes in measured hemodynamic parameters at doses equal to or less than 2 mg. per kilogram. Studies in isolated papillary muscle demonstrated no negative inotropic effects until concentrations of 1 X 10(-4). Disparate results were obtained with regard to heart rate reflecting the state of autonomic tone. Electrophysiologic studies in both anesthetized and conscious dogs demonstrated a significant depression of intraventricular conduction with no significant effect on AV nodal conduction; ventricular automaticity was not affected. Ajmaline did not alter digitalis-induced AV nodal conduction prolongation. However, Ajmaline dramatically altered or abolished ventricular arrhythmias secondary to acute ischemia. In conclusion, these studies demonstrate that Ajmaline specifically depresses intraventricular conduction, suggesting that this drug would be particularly effective in the treatment of re-entrant ventricular arrhythmias.
Ajmaline attenuates electrocardiogram characteristics of inferolateral early repolarization
Heart Rhythm 2012 Feb;9(2):232-9.PMID:21914496DOI:10.1016/j.hrthm.2011.09.013.
Background: J waves are the hallmark of both inferolateral early repolarization (ER) and Brugada syndrome. While Ajmaline, a class 1a antiarrhythmic drug, accentuates the J wave in Brugada syndrome, its effect on ER is unreported. Objective: To describe the effect of Ajmaline on the electrocardiogram in ER. Methods: We analyzed electrocardiograms before and after the administration of intravenous Ajmaline (1 mg/kg) in 31 patients with ER, 21 patients with Brugada type 1 electrocardiogram (Br), and 22 controls. ER was defined as J-point elevation of ≥1 mm with QRS slurring or notching in ≥2 inferolateral leads (I, aVL, II, III, aVF, V4-V6). Results: Ajmaline decreased mean J-wave amplitude in the ER group from 0.2 ± 0.15 mV at baseline to 0.08 ± 0.09 mV (P < .001). The QRS width prolonged significantly in all 3 groups, but the prolongation was significantly less in the ER group (+21 ms) than in the Br group (+36 ms; P < .001) or controls (+28 ms; P = .010). Decrease in mean inferolateral R-wave amplitude was similar in all the groups (ER group -0.14 mV; Br group -0.11 mV; controls -0.13 mV; P = ns), but mean inferolateral S-wave amplitude increased significantly less in the ER group (ER group +0.14 mV; Br group +16 mV; controls +0.20 mV; P < .001). Conclusions: Ajmaline significantly decreases the J-wave amplitude in ER and prolongs the QRS width significantly less than in patients with Br. This indicates a different pathogenesis for both disorders. The altered terminal QRS vector probably is responsible for the decrease in the J-wave amplitude in ER, although a specific effect of Ajmaline on J waves cannot be excluded.