• Journal of Ginseng Research
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• v.44 no.5
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• pp.717-724
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• 2020

Background: Malignant arrhythmias require drug therapy. However, most of the currently available antiarrhythmic drugs have significant side effects. Ginsenoside Rg2 exhibits excellent cardioprotective effects and appears to be a promising candidate for cardiovascular drug development. So far, the oral toxicity and antiarrhythmic effects of Rg2 have not been evaluated. Methods: Acute oral toxicity of Rg2 was assessed by the Limit Test method in mice. Subchronic oral toxicity was determined by repeated dose 28-day toxicity study in rats. Antiarrhythmic activities of Rg2 were evaluated in calcium chloride-induced arrhythmic rats. Antiarrhythmic mechanism of Rg2 was investigated in arrhythmic rats and H9c2 cardiomyocytes. Results: The results of toxicity studies indicated that Rg2 exhibited no single-dose (10 g/kg) acute oral toxicity. And 28-day repeated dose treatment with Rg2 (1.75, 3.5 and 5 g/kg/d) demonstrated minimal, if any, subchronic toxicity. Serum biochemical examination showed that total cholesterol in the high-dose cohort was dramatically decreased, whereas prothrombin time was increased at Day 28, suggesting that Rg2 might regulate lipid metabolism and have a potential anticoagulant effect. Moreover, pretreatment with Rg2 showed antiarrhythmic effects on the rat model of calcium chloride induced arrhythmia, in terms of the reduced duration time, mortality, and incidence of malignant arrhythmias. The antiarrhythmic mechanism of Rg2 might be the inhibition of calcium influx through L-type calcium channels by suppressing the phosphorylation of Ca²⁺/calmodulin-dependent protein kinase II. Conclusion: Our findings support the development of Rg2 as a promising antiarrhythmic drug with fewer side effects for clinical use.

• Proceedings of the PSK Conference
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• 2003.04a
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• pp.126.2-127
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• 2003

The therapeutic potential of currently available antiarrhythmic drugs is limited by their tendency to induce proarrhythmic and extracardiac side effects. An ideal antiarrhythmic agent would selectively prolong the action potential duration more in extraordinarily depolarized cardiac myocytes than in normal cells. and show tissue selectivity. Voltage-gated K+ (Kv) channels represent a structurally and functionally diverse group of membrane proteins. (omitted)

• Journal of Electrochemical Science and Technology
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• v.9 no.4
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• pp.292-300
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• 2018

The electrocatalytic oxidative behavior of an antiarrhythmic drug, procainamide hydrochloride (PAH) at the gold electrode surface has been examined using different voltammetric methods like cyclic, linear-sweep and differential pulse voltammetry. Voltammograms obtained in this study reveal that the electrode exhibit excellent electrocatalytic activity towards oxidation of the drug. The parameters that can affect the peak current at different pH, scan rate and concentration were evaluated. The number of electrons transferred was calculated. The current displayed a wide linear response ranging from 0.5 to $30.0{\mu}M$ with a limit of detection of 56.4 nM. The impact of potential interfering agents was also studied. The electrode displayed wide advantages such as simple sample preparation, appreciable repeatability, reproducibility and also high sensitivity. Furthermore, the feasibility of the proposed method was successfully demonstrated by determining PAH in the spiked human biological sample.

• Proceedings of the PSK Conference
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• 2002.10a
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• pp.247.1-247.1
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• 2002

A number of patients suffering from atrial fibrillation are increasing and many cardiologists are trying to develop the ideal antiarrhythmic drugs for atrial fibrillation. Previously, we found out that CW-2202, a furanocoumarin derivative inhibited the hKvl.5 current expressing predominantly in human atrium without affecting the HERG current expressing mainly in ventricle. (omitted)

• Proceedings of the PSK Conference
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• 2001.10a
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• pp.140.3-141
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• 2001

• Proceedings of the PSK Conference
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• 2002.04a
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• pp.108.1-108.1
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• 2002

• Korean Journal of Clinical Pharmacy
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• v.26 no.1
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• pp.84-95
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• 2016

Objective: Atrial fibrillation (AF) guidelines have been published in the USA and Europe. Recently, the USA and Europe have updated their guidelines, respectively. These new AF guidelines help in addressing key management issues in clinical situations. This study, therefore, systematically compared guidelines for rate and rhythm control pharmacotherapy of patients with AF between the USA (American College of Cardiology and American Heart Association, ACC/AHA) and Europe (European Society of Cardiology, ESC). Methods: This study investigated and compared American guidelines (2014) and European guidelines (2010 and 2012). Results: Generally, there are four meaningful differences between ACC/AHA and ESC guidelines. Important differences are treatment classification system, level of recommendation, drug list, and dosage. In addition, ACC/AHA described pharmacokinetic drug interactions for antiarrhythmic drugs. ESC emphasized ECG and atrioventricular nodal slowing as feature of antiarrhythmic drugs. Conclusion: This research addresses important use of anti-arrhythmic drugs and movement to accept recent recommendations in Korea. For the successful application of the guidelines, a role of pharmacists is crucial in clinical situation.

• Biomolecules & Therapeutics
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• v.14 no.2
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• pp.102-105
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• 2006

We examined the effects of psoralen derivatives on a rapidly activating delayed rectifier $K^+$ channel (hKv1.5) cloned from human heart and stably expressed in $Ltk^-$ cells. Using the whole cell configuration of the patch-clamp technique, we found that the five psoralen derivatives inhibited hKv1.5 current. Especially, 4-(2-Propenyloxy)-7H-furo[3,2-g][1]benzopyran-7-one (compound 5) was more potent than the inhibition of the hKv1.5 current of psoralen. The compound 5 inhibited the hKv1.5 current in a concentration-, time-, and voltage-dependent manner. These results suggest that the compound 5 is an excellent candidate as an antiarrhythmic drug for atrial fibrillation.

• The Korean Journal of Pharmacology
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• v.11 no.2
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• pp.9-17
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• 1975

The adrenergic blocking activity and refractory period of cardiac muscle on isolated rabbit atria were measured after administration of Scutellaria. In rabbits and cats the antiarrhythmic action of Scutellaria on atrial and ventricular arrhythmias produced by epinephrine or ouabain was examined and also compared with that of propranolol and quinidine. The alcoholic extract of Scutellaria produced a marked decrease in heart rate and contractile amplitude of the isolated rabbit atria. Pretreatment with Scutellaria rendered the atria to fail to respond to epinephrine, indicating that this crude drug possesses an adrenergic blocking activity. The extract produced a marked prolongation of the refractory period of atrial muscle. The extract effectively abolished the spontaneous arrhythmia occurring in the isolated rabbit atria. As propranolol and quinidine it also suppressed the atrial arrhythmia induced by ouabain. The extract prevented, as propranolol and quinidine, the induction of ventricular arrhythmia arising from excessive dose of epinephrine in anesthetized rabbits and cats. With regard to the ventricular arrhythmia induced by a continuous infusion of ouabain, the alcoholic extract of Scutellaria exerted some suppressive effect in anesthetized rabbits but no effect on cats. From the above results, it may be concluded that Scutellaria is effective against atrial and ventricular arrhythmias. The antiarrhythmic effects of this drug may be the result of adrenergic beta receptor blocking and cardiac depressive activities including prolongation of the refractory period of cardiac muscle.

• The Korean Journal of Physiology and Pharmacology
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• v.22 no.5
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• pp.597-605
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• 2018

In this study, we demonstrated the inhibitory effect of the Class Ic antiarrhythmic agent propafenone on voltage-dependent $K^+$ (Kv) channels using freshly isolated coronary artery smooth muscle cells from rabbits. The Kv current amplitude was progressively inhibited by propafenone in a dose-dependent manner, with an apparent $IC_{50}$ value of $5.04{\pm}1.05{\mu}M$ and a Hill coefficient of $0.78{\pm}0.06$. The application of propafenone had no significant effect on the steady-state activation and inactivation curves, indicating that propafenone did not affect the voltage-sensitivity of Kv channels. The application of train pulses at frequencies of 1 or 2 Hz progressively increased the propafenone-induced inhibition of the Kv current. Furthermore, the inactivation recovery time constant was increased after the application of propafenone, suggesting that the inhibitory action of propafenone on Kv current is partially use-dependent. Pretreatment with Kv1.5, Kv2.1 or Kv7 inhibitor did not change the inhibitory effect of propafenone on the Kv current. Together, these results suggest that propafenone inhibits the vascular Kv channels in a dose- and use-dependent manner, regardless of $Na^+$ channel inhibition.