Moricizine
(Synonyms: 乙吗噻嗪) 目录号 : GC36648
Moricizine可抗心律失常。
Cas No.:31883-05-3
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
Moricizine is an antiarrhythmia agent used primarily for ventricular rhythm disturbances.Target: Sodium ChannelMoricizine is an antiarrhythmia agent used primarily for ventricular rhythm disturbances. Moricizine works by inhibiting the rapid inward sodium current across myocardial cell membranes. Moricizine induced the tonic block of INa with the apparent dissociation constant (Kd,app) of 6.3 microM at -100 mV and 99.3 microM at -140 mV. Moricizine at 30 microM shifted the h infinity curve to the hyperpolarizing direction by 8.6 +/- 2.4 mV. Moricizine also produced the phasic block of INa, which was enhanced with the increase in the duration of train pulses, and was more prominent with a holding potential (HP) of -100 mV than with an HP of -140 mV. Moricizine would exert an antiarrhythmic action on atrial myocytes, as well as on ventricular myocytes, by blocking Na+ channels with a high affinity to the inactivated state and a slow dissociation kinetics [1].
[1]. Ahmmed, G.U., et al., Analysis of moricizine block of sodium current in isolated guinea-pig atrial myocytes. Atrioventricular difference of moricizine block. Vascul Pharmacol, 2002. 38(3): p. 131-41.
| Cas No. | 31883-05-3 | SDF | |
| 别名 | 乙吗噻嗪 | ||
| Canonical SMILES | O=C(OCC)NC(C=C1N2C(CCN3CCOCC3)=O)=CC=C1SC4=C2C=CC=C4 | ||
| 分子式 | C22H25N3O4S | 分子量 | 427.52 |
| 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 | 2.3391 mL | 11.6954 mL | 23.3907 mL |
| 5 mM | 0.4678 mL | 2.3391 mL | 4.6781 mL |
| 10 mM | 0.2339 mL | 1.1695 mL | 2.3391 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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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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Pharmacokinetics of Moricizine HCl
Am J Cardiol 1987 Oct 16;60(11):35F-39F.PMID:3310583DOI:10.1016/0002-9149(87)90718-1.
Moricizine HCl is a phenothiazine derivative with antiarrhythmic properties. It was developed in the USSR and is now undergoing clinical evaluation. Although preliminary work has shown Moricizine HCl to be effective in treating both atrial and ventricular arrhythmias, little is known of its pharmacokinetics. There is a 4-fold variability in range for its elimination half-life and in volumes of distribution and clearance. There is a linear relation for peak plasma levels and area under the plasma concentration/time curve with regard to single-dose administration of Moricizine HCl. The bioavailability of Moricizine HCl connotes extensive first-pass effect, or presystemic metabolism. Very little of Moricizine is excreted unchanged; it is extensively metabolized to certain compounds that are present in plasma for extended periods. Moricizine is extensively (92% to 95%) bound to plasma protein. Its coadministration with cimetidine leads to additive systemic effects; however, there is no evidence of alterations in steady-state levels when Moricizine HCl is coadministered with digoxin. Because Moricizine is a drug with active metabolites, its concentration/effect profile is complex; this poses a challenge for accurate dose titration. This may, however, be a helpful challenge in that the metabolites may one day prove useful in therapy. This surmise warrants further study.
Clinical pharmacokinetics of Moricizine
Am J Cardiol 1990 Feb 20;65(8):21D-25D; discussion 68D-71D.PMID:2407090DOI:10.1016/0002-9149(90)91413-z.
Moricizine is well absorbed after oral administration and undergoes extensive first-pass metabolism. The drug has a large apparent volume of distribution (approximately 4 liters/kg), exhibits extensive plasma protein binding (approximately 95%) and produces at least 30 metabolites. Indirect evidence indicates that some of those metabolites may be pharmacologically active. The elimination half-life of Moricizine is 2 to 6 hours, but its duration of antiarrhythmic action is much longer suggesting active metabolites. Moricizine induces its own metabolism with no change in pharmacologic effect. It also induces the metabolism of theophylline and specific pathways of antipyrine. Cimetidine reduces metabolism of Moricizine but does not alter its pharmacologic effects. This observation provides further support for the hypothesis that the metabolites of Moricizine contribute to the pharmacologic actions during therapy and indicate that plasma level monitoring is not likely to be of value. There are no known clinically significant pharmacokinetic interactions between Moricizine and digoxin, warfarin or propranolol. Excessive prolongation of the PR interval has been seen in some patients receiving both digoxin and Moricizine, probably due to additive electrophysiologic effects of the 2 drugs.
Moricizine. A review of its pharmacological properties, and therapeutic efficacy in cardiac arrhythmias
Drugs 1990 Jul;40(1):138-67.PMID:2202581DOI:10.2165/00003495-199040010-00007.
Moricizine (moracizine, ethmozine) is an orally active phenothiazine derivative with direct myocardial Class I antiarrhythmic activity and minimal CNS effects. Placebo-controlled studies have confirmed its efficacy in suppressing nonmalignant ventricular arrhythmias (premature ventricular complexes, couplets and runs of nonsustained ventricular tachycardia), including those refractory to previous antiarrhythmic therapy. Preliminary findings have indicated that Moricizine is also effective in suppressing atrial ectopic activity, atrioventricular nodal re-entry tachycardia and Wolff-Parkinson-White tachycardias involving accessory pathways. As with other oral antiarrhythmics, malignant ventricular arrhythmias (sustained ventricular tachycardia and ventricular fibrillation) have been shown, both on noninvasive monitoring and programmed electrical stimulation, to be less susceptible to suppression by Moricizine than nonmalignant ventricular arrhythmias. The therapeutic potential of Moricizine is enhanced by its relatively low incidence of extra-cardiac adverse effects (predominantly gastrointestinal and neurological) and its lack of significant cardiodepressant activity in patients with normal or mildly to moderality depressed left ventricular function. Moricizine has proved to be more effective than disopyramide and propranolol in suppressing ventricular ectopic activity, of comparable efficacy to quinidine, but less effective than encainide and flecainide. The drug appears to be particularly suited to the suppression of ventricular ectopy in patients with preexisting left ventricular dysfunction. Further studies are required to confirm its long term efficacy and effects on mortality when used prophylactically in patients at increased risk of sudden cardiac death.
Moricizine prevents atrial fibrillation by late sodium current inhibition in atrial myocytes
J Thorac Dis 2022 Jun;14(6):2187-2200.PMID:35813708DOI:10.21037/jtd-22-534.
Background: Enhanced late sodium current (INaL) is reportedly related to an increased risk of atrial fibrillation (AF). Moricizine, as a widely used anti-arrhythmia drug for suppressing ventricular tachycardia, has also been shown to prevent paroxysmal AF. However, the mechanism of its therapeutic effect remains poorly understood. Methods: Angiotensin II (Ang II) was induced in C57Bl/6 mice (male wild-type) for 4 weeks to increase the susceptibility of AF, and acetylcholine-calcium chloride was used to induce AF. The whole-cell patch-clamp technique was used to detect INaL from isolated atrial myocytes. The expression of proteins in atrial of mice and HL-1 cells were examined by Western-blot. Results: The results showed that Moricizine significantly inhibited Ang II-mediated atrial enlargement and reduced AF vulnerability. We found that the densities of INaL were enhanced in Ang II-treated left and right atrial cardiomyocytes. Simultaneously, the Ang II-induced increase in INaL currents density was alleviated by the administration of Moricizine, and no alteration in Nav1.5 expression was observed. In normal isolated atrial myocytes, Moricizine significantly reduced Sea anemone toxin II (ATX II)-enhanced INaL density with a reduction of peak sodium currents. In addition, Moricizine reduced the Ang II-induced upregulation of phosphorylated calcium/calmodulin-dependent protein kinase-II (p-CaMKII) in both the left and right atria. In HL-1 cells, Moricizine also reduced the upregulation of p-CaMKII with Ang II and ATX II intervention, respectively. Conclusions: Our results indicate that Ang II enhances the INaL via activation of CaMKII. Moricizine inhibits INaL and reduces CaMKII activation, which may be one of the mechanisms of Moricizine suppression of AF.
Cardiac electrophysiologic effects of Moricizine hydrochloride
Am J Cardiol 1990 Feb 20;65(8):15D-20D; discussion 68D-71D.PMID:2407089DOI:10.1016/0002-9149(90)91412-y.
Moricizine is a class I antiarrhythmic drug. In preclinical studies, it produces a concentration-dependent decrease in the maximal rate of phase 0 depolarization, speeds repolarization of phases 2 and 3, and decreases the action potential duration and effective refractory period duration in cardiac Purkinje fibers. It has no effect on the slope of phase 4 depolarization, but suppresses normal automaticity in vitro and in vivo and suppresses abnormal automaticity in depolarized Purkinje fibers. Also, it suppresses early afterdepolarizations, delayed afterdepolarizations and triggered activity. In patients, Moricizine has minimal effects on the normal sinus node, slows conduction in the atrium, atrioventricular node, His-Purkinje system and ventricular myocardium and has little effect on the atrial and ventricular refractoriness. The intensity of Moricizine action on the atrioventricular node, His-Purkinje system and JT interval are dose-related. Co-administration of digoxin and Moricizine intensified the lengthening of the PR, AH and HV intervals, and produced more shortening of the JT interval. Patients in whom Moricizine was efficacious had a significantly greater lengthening of the AH and QRS intervals than those in whom Moricizine was not efficacious. In some patients with sinus node dysfunction, Moricizine produced sinus bradycardia, increased sinus node recovery time, and produced second-degree or complete sinoatrial block.