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Antibiotic nitrofurantoi capable of serving as novel antiarrhythmic drug

A technology for nitrofurantoin and arrhythmia, which is used in drug combinations, pharmaceutical formulations, cardiovascular system diseases, etc.

Pending Publication Date: 2020-02-28
SHANXI MEDICAL UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0018] But so far, there is only such an I as zacopride K1 Specific agonists are publicly reported

Method used

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  • Antibiotic nitrofurantoi capable of serving as novel antiarrhythmic drug
  • Antibiotic nitrofurantoi capable of serving as novel antiarrhythmic drug

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0028] Embodiment one: the screening of nitrofurantoin

[0029]IK1 selective agonist - zacopride (zacopride), by stimulating IK1, can increase the negative value of the resting potential (hyperpolarization), and slightly shorten the duration of the action potential. The drug repositioning platform based on omics big data seeks the analogues of zacopride. The human colorectal cancer cell line HCT116 was incubated with zacopride for 24 hours, and transcriptome sequencing (RNA-seq) was performed. Two groups of "Ctl_VS_Za_1 (control) Group VS zacopride 1 μM) and Ctl_VS_Za_40 (control group VS zacopride 40 μM)” were verified. After the difference results were consistent, two groups of differential genes were obtained: Ctl_VS_Za_1 group had 226 differential genes, 187 were up-regulated, and 39 were down-regulated. 302 differential genes in Ctl_VS_Za_40 group, 250 up-regulated and 52 down-regulated. The two groups of differentially expressed genes were imported into the drug reposit...

Embodiment 2

[0030] Example 2: Detecting the effect of nitrofurantoin on the resting potential and action potential of left ventricular myocytes.

[0031] (1) Experimental method: Patch clamp whole cell recording, voltage clamp mode recording membrane current, current clamp mode recording membrane potential

[0032] (2) Observation indicators: rat ventricular muscle resting potential (RMP), action potential amplitude (APA) and duration (APD) before and after drug action 50 ,APD 90 ) The change.

[0033] because I K1 It is the main ion current that determines the resting potential (RMP) level and the terminal repolarization of the action potential (AP) phase 3. The inventors first observed the effect of the antibiotic Nitrofurantoi on the resting potential and action potential of left ventricular myocytes.

[0034] (1) Acute isolation of rat left ventricular cardiomyocytes by collagenase method

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Abstract

The invention discloses application of nitrofurantoi in preparing drug for treating arrhythmia. It is found for the first time that nitrofurantoi can effectively serve as an IK1 specific agonist, haseffect similar to that of zacopride and can serve as antiarrhythmic drug, so that a new treatment way which is effective and safe is provided.

Description

technical field [0001] The invention relates to a cardiovascular disease drug, in particular to the application of nitrofurantoin in the preparation of drugs for treating arrhythmia. Background technique [0002] Arrhythmia refers to the abnormality of heartbeat frequency and rhythm, and severe arrhythmia is often one of the main causes of death in patients with cardiovascular diseases. The mechanism of severe arrhythmia is very complicated, and it is often not a single mechanism, but at its root, there are changes in the functional activities of myocardial ion channels, and the changes in ion currents caused by this will affect the occurrence and shape of action potentials. Those drugs that alter the action potential may thus have a proarrhythmic risk or an antiarrhythmic effect. [0003] At present, almost all antiarrhythmic drugs in clinical use are various ion channel blockers, and their main targets act on Na . Kv , Ca ion channels. Disorder drugs fall into four categ...

Claims

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Application Information

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IPC IPC(8): A61K31/4178A61P9/06
CPCA61K31/4178A61P9/06
Inventor 吴博威刘清华贺培凤卢学春于琦郝亚楠吕艳华
Owner SHANXI MEDICAL UNIV
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