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Application of donepezil in preparation of medicine for treating arrhythmia

A donepezil and antiarrhythmic technology, applied in the field of medicine, can solve problems such as bradycardia, and achieve the effects of less toxic and side effects, prolonging the action potential duration, and prolonging the effective refractory period

Pending Publication Date: 2022-07-22
YANGZHOU ZHONGBAO PHARMA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Clinical Data Show Donepezil May Cause Bradycardia

Method used

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  • Application of donepezil in preparation of medicine for treating arrhythmia
  • Application of donepezil in preparation of medicine for treating arrhythmia
  • Application of donepezil in preparation of medicine for treating arrhythmia

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0026] Example 1: Effect of donepezil on fast action potential (AP) of guinea pig ventricular papillary muscle cells

[0027] Guinea pigs were used in this experiment. Take 30 guinea pigs, weighing 350-400 g, male or female. The guinea pigs were decapitated and exsanguinated, and the hearts were rapidly isolated to 100% O. 2 In saturated benchtop solution (NaCl 147mM; KCl 5.4mM; CaCl 2 1.8mM; MgCl1.05mM; HEPES 10mM; Glucose 11mM; pH 7.4), rapidly separate right ventricular papillary muscle (choose a diameter of 0.4-0.8mm), apply a preload of about 0.5g to the specimen from the horizontal direction and fix it on the bottom of a 10mL constant temperature bath on a silicone sheet to last for 100% O 2 , the temperature is 36 ± 0.5 ℃ desktop liquid perfusion, flow rate 3mL / min, equilibrated for 2h for the experiment.

[0028] AP was recorded using standard glass microelectrode techniques. Ventricular tissue samples were treated with balanced salt solution (O 2 Saturated modi...

Embodiment 2

[0032] Example 2: Chloroform-induced arrhythmia test in mice

[0033] Kunming mice were used in this experiment. Take 60 mice, weighing 25-30g, half male and half male, and randomly divided into 3 groups with 20 mice in each group: negative control group (normal saline), positive (verapamil) group (4 mg / kg) ), donepezil (2mg / kg) group. Each group was successively injected with the drug or an equal volume of normal saline into the tail vein of the mice according to the administration volume of 0.1 mL / 10 g, and put them into a 500 mL beaker containing 4 mL of chloroform cotton balls. Take it out of the beaker, quickly open its chest cavity, expose the mouse heart, visually check whether the mouse arrhythmia occurs or not, record the results and compare them, as shown in Table 2. It can be seen from Table 2 that compared with normal saline, donepezil can significantly reduce the incidence of chloroform-induced arrhythmia.

[0034] Table 2 The effect of donepezil on chloroform-...

Embodiment 3

[0037] Example 3: Aconitine-induced arrhythmia experiment in rats

[0038]SD rats were used in this experiment. 30 SD rats, weighing 180-220 g, half male and half male, were randomly divided into 3 groups, namely model group, amiodarone group (0.5 mg / kg, tail vein injection) and donepezil group (5 mg / kg) , intragastric administration), 5 males and 5 males in each group. After 30 minutes of administration (10 minutes after administration of the positive group), the back was fixed after anesthesia, the neck vein was incised, and the physiological signal acquisition system was connected. Aconitine 20μg / kg was injected within 1min, followed by a constant-speed bolus injection of 0.4μg / min by a micro-infusion pump to induce arrhythmia. The occurrence time of ventricular premature beat, ventricular tachycardia, ventricular fibrillation and cardiac arrest were recorded and converted into the cumulative dose of aconitine. The results are shown in Table 3, Table 4, figure 2 and i...

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Abstract

The invention relates to the technical field of medicines, and discloses application of donepezil in preparation of a medicine for treating arrhythmia, so that a safe and effective medicine with small toxic and side effects is provided for clinical treatment of arrhythmia. The donepezil can effectively prolong the action potential time history of myocardial cells and prolong the effective refractory period, can be further developed into a medicine for treating arrhythmia, and has a wide application prospect.

Description

technical field [0001] The invention belongs to the technical field of medicine, and particularly relates to the application of donepezil in the preparation of a drug for treating arrhythmia. Background technique [0002] Arrhythmias are abnormalities in the rate or rhythm of the heartbeat, caused by abnormalities in the frequency, rhythm, origin, conduction rate, or sequence of activation of cardiac impulses. Many factors can lead to arrhythmias, such as heart attack, congenital heart defects, smoking, and alcoholism. Typical symptoms of arrhythmia include palpitations, fatigue, etc., and as the disease progresses, dizziness, fainting, shortness of breath or chest pain may even lead to sudden death. While some arrhythmia symptoms are not serious, patients are prone to complications such as stroke or heart failure. [0003] Although radiofrequency ablation, automatic cardioverter-defibrillator and other treatment methods are available, antiarrhythmic drugs are still an imp...

Claims

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Application Information

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IPC IPC(8): A61K31/445A61P9/06
CPCA61K31/445A61P9/06
Inventor 蔡浩毕爱静张广明张冠亚韩晓秋卢诚
Owner YANGZHOU ZHONGBAO PHARMA
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