Pilsicainide (hydrochloride)
(Synonyms: 盐酸吡西卡呢,SUN-1165; Pilzicainide(hydrochloride)) 目录号 : GC49193
A class Ic antiarrhythmic agent
Cas No.:88069-49-2
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >95.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Pilsicainide is a class Ic antiarrhythmic agent.1,2 It shortens action potential duration in canine Purkinje fibers, as well as increases the ratio of the effective refractory period to the duration of action potential in guinea pig atrial muscle strips, when used at a concentration of 10 µg/ml.1 Pilsicainide (3-10 mg/kg) restores sinus rhythm in a canine model of ventricular multifocal arrhythmias.2 It also suppresses arrhythmias induced by ouabain or halothane and epinephrine in dogs. Formulations containing pilsicainide have been used in the treatment of supraventricular and ventricular tachycardia.
1.Hattori, Y., Inomata, N., Aisaka, K., et al.Electrophysiological actions of N-(2,6-dimethylphenyl)-8-pyrrolizidine-acetamide hydrochloride hemihydrate (SUN 1165), a new antiarrhythmic agentJ. Cardiovasc. Pharmacol.8(5)998-1002(1986) 2.Aisaka, K., Hidaka, T., Inomata, N., et al.N-(2,6-Dimethylphenyl)-8-pyrrolizidineacetamide hydrochloride hemihydrate (SUN 1165): A new potent and long-acting antiarrhythmic agentArzneimittelforschung35(8)1239-1245(1985)
| Cas No. | 88069-49-2 | SDF | |
| 别名 | 盐酸吡西卡呢,SUN-1165; Pilzicainide(hydrochloride) | ||
| Canonical SMILES | O=C(CC12N(CCC2)CCC1)NC3=C(C)C=CC=C3C.Cl | ||
| 分子式 | C17H24N2O·HCl | 分子量 | 308.9 |
| 溶解度 | DMF: 20 mg/ml,DMSO: 25 mg/ml,Ethanol: 25 mg/ml,PBS (pH 7.2): 10 mg/ml | 储存条件 | -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 | 3.2373 mL | 16.1865 mL | 32.3729 mL |
| 5 mM | 0.6475 mL | 3.2373 mL | 6.4746 mL |
| 10 mM | 0.3237 mL | 1.6186 mL | 3.2373 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。
Pilsicainide
Drugs 2010 Mar 5;70(4):455-67.PMID:20205487DOI:10.2165/11204960-000000000-00000.
Pilsicainide is a class Ic antiarrhythmic agent used for the treatment of supraventricular and ventricular tachycardia. The pharmacodynamic effects of Pilsicainide are achieved via selective sodium channel blockade. In randomized, multicentre trials in patients with atrial fibrillation, restoration of sinus rhythm was achieved in significantly more patients treated with a single oral dose of Pilsicainide than those who received placebo, and in a numerically higher proportion of oral Pilsicainide than intravenous disopyramide recipients. In another well designed trial in patients with persistent atrial fibrillation, the proportion of patients whose arrhythmia converted to normal sinus rhythm was significantly higher among those randomized to receive 2 weeks of oral Pilsicainide therapy than among patients who received placebo. Over a 1-year period, both Pilsicainide and cibenzoline (another class Ic agent) were effective in preventing recurrence of atrial fibrillation in a substantial proportion of patients in a single-centre crossover trial. There were no between-group differences in the subgroup of patients with shorter-duration atrial fibrillation, but actuarial results over 1 year significantly favoured cibenzoline over Pilsicainide in patients with longer-duration atrial fibrillation. Both oral and intravenous Pilsicainide have demonstrated efficacy in ventricular tachyarrhythmias, including ventricular extrasystole. Clinical trial and postmarketing surveillance data indicate that Pilsicainide is generally well tolerated in most patients.
Pharmacokinetics of Pilsicainide hydrochloride for injection in healthy Chinese volunteers: a randomized, parallel-group, open-label, single-dose study
Clin Ther 2014 Feb 1;36(2):255-63.PMID:24480637DOI:10.1016/j.clinthera.2013.12.015.
Background: Pilsicainide hydrochloride is a class IC antiarrhythmic agent used for the treatment of supraventricular and ventricular arrhythmias and atrial fibrillation. Objective: The objective of the present study was to determine the pharmacokinetics (PK) of a Pilsicainide hydrochloride injection in healthy Chinese adults. The study was conducted to meet China State Food and Drug Administration requirements for the marketing of the new generic formulation of Pilsicainide hydrochloride. Methods: This Phase I, randomized, parallel-group, open-label, single-dose PK study was conducted in healthy Chinese volunteers. Subjects were randomized to receive a single dose of 0.25-, 0.50-, and 0.75-mg/kg Pilsicainide hydrochloride with a 10-minute intravenous infusion. Serial blood and urine samples were collected up to 24 hours after dosing; drug concentrations in plasma and urine were then determined by using LC-MS/MS. The PK parameters of Pilsicainide were calculated from the plasma concentration-time data according to noncompartmental methods. Safety profile was evaluated by monitoring adverse events, clinical laboratory parameters, and the results of 12-lead ECGs. Results: Thirty healthy volunteers (mean [SD] age, 28.0 [4.95] years; weight, 59.3 [6.51] kg; height, 165.0 [7.25] cm; body mass index, 21.7 [1.94] kg/m(2)) were randomly divided into 3 groups, each consisting of 5 men and 5 women. After single-dose intravenous administration of 0.25, 0.50, and 0.75 mg/kg of Pilsicainide hydrochloride, mean Cmax was 0.34 (0.11), 0.54 (0.15), and 1.05 (0.19) μg/mL, respectively; AUC0-24 was 0.76 (0.12), 1.61 (0.37), and 2.61 (0.46) h · μg/mL; and AUC0-∞ was 0.79 (0.13), 1.71 (0.46), and 2.72 (0.50) h · μg/mL. The ranges for t½z, CL, and Vz were 5.19 to 5.98 hours, 4.73 to 5.44 mL/min/kg, and 2.23 to 0.58 L/kg, respectively. The mean urinary recovery rate within 24 hours was 75.0% (12.0%), 65.0% (19.2%), and 66.4% (14.1%). Men and women had significantly different AUC0-24 values in the 0.50-mg/kg dose group (P = 0.044), and Vz showed significant differences between men and women in all 3 dose groups (P = 0.001). According to ECG parameters, PR intervals were significantly prolonged after administration at all 3 doses (P = 0.034, P < 0.001, and P = 0.034); no significant changes were seen in QRS width, QTc interval, or other parameters. Conclusions: Pilsicainide hydrochloride demonstrated linear PK, and the increase in the exposure of Pilsicainide (AUC0-24 and AUC0-∞) was dose proportional after single doses of 0.25, 0.50, and 0.75 mg/kg. All 3 Pilsicainide hydrochloride doses were well tolerated in these Chinese volunteers. ChiCTR-ONC-13003546.
Pilsicainide for atrial fibrillation
Drugs 2006;66(16):2067-73.PMID:17112301DOI:10.2165/00003495-200666160-00003.
Pilsicainide is a class IC antiarrhythmic drug, which has a pure sodium channel blocking action with slow recovery pharmacokinetics. In experimental studies, Pilsicainide has a depressant effect on intra-atrial conduction and a prolonging effect on the atrial effective refractory period (ERP). In patients with paroxysmal atrial fibrillation (AF), Pilsicainide significantly prolonged the ERP of the distal pulmonary vein (PV), PV-left atrium (LA) junction and LA, and the conduction time from the distal PV to the PV-LA junction. In some patients, PV-LA conduction block has been observed just before pilsicainide-induced termination of AF; this isolation of the PV may provide a new insight into the mechanism of pharmacological conversion of AF. Hybrid therapy with Pilsicainide and PV isolation (by radiofrequency catheter ablation) appears to be an effective therapeutic approach for AF. The pharmacological PV isolation by Pilsicainide and its suppression of focal discharges from atrial tissue may prevent the development of AF after unsuccessful ablation.
[Antiarrhythmic effects of Pilsicainide hydrochloride and effects on cardiac function and ECG in dogs: comparison with disopyramide]
Nihon Yakurigaku Zasshi 2000 May;115(5):295-308.PMID:10872181DOI:10.1254/fpj.115.295.
Antiarrhythmic effects and cardiovascular effects of Pilsicainide hydrochloride were compared with those of disopyramide in a canine model of coronary ligation-induced ventricular arrhythmias and anesthetized dogs. Pilsicainide (1.25, 2.5 and 5 mg/kg) and disopyramide (2.5 and 5 mg/kg) decreased the arrhythmic ratio ¿(ventricular arrhythmias/total heart rate) x 100¿ dose-dependently. Pilsicainide at 2.5 and 5 mg/kg and disopyramide at 5 mg/kg suppressed ventricular arrhythmias more than 50%. The effective dose of Pilsicainide was lower than that of disopyramide, but the effective plasma concentration of Pilsicainide was between 3 and 8 micrograms/ml, which was almost the same as that of disopyramide. In anesthetized dogs, both drugs decreased LV dP/dt max in almost the same concentration-dependent manner. PQ-interval was prolonged by Pilsicainide, but not by disopyramide. QRS and QTc were prolonged by both drugs in a concentration-dependent manner. However, the prolongation of QTc by disopyramide was provoked at lower plasma concentrations than by Pilsicainide. Because the excessive prolongation of QTc lead to the lethal arrhythmias such as torsades de pointes, Pilsicainide may be useful as an injectable antiarrhythmic agent superior to disopyramide.
Molecular mechanisms underlying the pilsicainide-induced stabilization of hERG proteins in transfected mammalian cells
J Arrhythm 2017 Jun;33(3):226-233.PMID:28607619DOI:10.1016/j.joa.2016.09.003.
Background: Pilsicainide, classified as a relatively selective Na+ channel blocker, also has an inhibitory action on the rapidly-activating delayed-rectifier K+ current (IKr ) through human ether-a-go-go-related gene (hERG) channels. We studied the effects of chronic exposure to Pilsicainide on the expression of wild-type (WT) hERG proteins and WT-hERG channel currents, as well as on the expression of mutant hERG proteins, in a heterologous expression system. Methods: HEK293 cells stably expressing WT or mutant hERG proteins were subjected to Western blotting, immunofluorescence microscopy and patch-clamp experiments. Results: Acute exposure to Pilsicainide at 0.03-10 μM influenced neither the expression of WT-hERG proteins nor WT-hERG channel currents. Chronic treatment with 0.03-10 μM Pilsicainide for 48 h, however, increased the expression of WT-hERG proteins and channel currents in a concentration-dependent manner. Chronic treatment with 3 μM Pilsicainide for 48 h delayed degradation of WT-hERG proteins and increased the channels expressed on the plasma membrane. A cell membrane-impermeant Pilsicainide derivative did not influence the expression of WT-hERG, indicating that Pilsicainide stabilized the protein inside the cell. Pilsicainide did not influence phosphorylation of Akt (protein kinase B) or expression of heat shock protein families such as HSF-1, hsp70 and hsp90. E4031, a chemical chaperone for hERG, abolished the Pilsicainide effect on hERG. Chronic treatment with Pilsicainide could also increase the protein expression of trafficking-defective mutant hERG, G601S and R752W. Conclusions: Pilsicainide penetrates the plasma membrane, stabilizes WT-hERG proteins by acting as a chemical chaperone, and enhances WT-hERG channel currents. This mechanism could also be applicable to modulations of certain mutant-hERG proteins.