Effects of zatebradine on ouabain-, two-stage coronary ligation- and epinephrine-induced ventricular tachyarrhythmias

Furukawa, Yoshiko; Xue, Yixue; Chiba, Shigetoshi; Hashimoto, Keitaro

doi:10.1016/0014-2999(95)00880-2

Cited by 9 publications

(3 citation statements)

References 28 publications

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“…The pattern of drug effects are similar to that obtained using the two-stage coronary ligation arrhythmias, namely, that the Na + -channel-blocking drugs suppressed these digitalis arrhythmias and the effective plasma concentrations are closely related to their in vitro Na + -channel-blocking concentrations (5, 15, 16, 18 -40). Zatebradine did not suppress the two-stage coronary ligation arrhythmia, but digitalis arrhythmia was suppressed by a high dose of intravenous 1.5 mg/ kg bolus injection (57). The mechanism of this effect might be either due to I f block or other channel effects, but there was no supporting data of plasma concentration determination and also there were no other I f blockers available for our study.…”

Section: -2-3 Antiarrhythmic Drugsmentioning

confidence: 65%

Arrhythmia Models for Drug Research: Classification of Antiarrhythmic Drugs

Hashimoto

2007

J Pharmacol Sci

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Abstract. The aim of this study was to classify antiarrhythmic drugs based on their effectiveness on 6 in vivo arrhythmia models, mainly using dogs. The models were produced by two-stage coronary ligation, digitalis, halothane-adrenaline, programmed electrical stimulation in old myocardial infarction dogs, coronary artery occlusion / reperfusion, or chronic atrioventricular block. Na + -channel-blocking drugs suppressed two-stage coronary ligation and digitalis arrhythmias. Ca 2+ -channel blockers and β-blockers suppressed halothane-adrenaline arrhythmia. Positive inotropic drugs aggravated halothane-adrenaline arrhythmia, but did not aggravate digitalis arrhythmia. K + -channel blockers suppressed programmed electrical stimulation induced arrhythmia, but induced torsades de pointes type arrhythmia in chronic atrioventricular block dogs and aggravated halothane-adrenaline arrhythmia. Na

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Section: -2-3 Antiarrhythmic Drugsmentioning

confidence: 65%

Arrhythmia Models for Drug Research: Classification of Antiarrhythmic Drugs

Hashimoto

2007

J Pharmacol Sci

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“…HRV is a valuable tool to detect sympathetic and parasympathetic functions of the ANS [22] . There is overwhelming evidence in human and animal models that spectral power in the HF range in HRV reflects parasympathetic activity and that L/H ratio reflects sympathetic activity tones in the heart [13,20,[23][24][25] . Although zatebradine is currently prescribed in several clinical applications, only a few reports are available demonstrating its effects on HRV.…”

Section: Discussionmentioning

confidence: 99%

Three Different Bradycardic Agents, Zatebradine, Diltiazem and Propranolol, Distinctly Modify Heart Rate Variability and QT-Interval Variability

Yamabe

Sanyal²,

Miyamoto³

et al. 2007

Pharmacology

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Zatebradine, diltiazem and propranolol are all antiarrhythmic agents, and all induce bradycardia, but each is known to have a different initial molecular mechanism: zatebradine is a channel blocker of the hyperpolarization-activated inward current (I_f ); diltiazem is a blocker of the L-type Ca²⁺ channel (I_CaL), and propranolol is a β-blocker. To further investigate the mechanisms underlying their clinical effects, we studied their effects on heart rate variability (HRV) and QT-interval variability (QTV). To this end, guinea pigs were treated with either zatebradine (1.5 mg/kg, i.p.), diltiazem (40 mg/kg, i.p.) or propranolol (20 mg/kg, i.p.). A dose of each agent that decreased HR by 20–22% was used in this study. HRV and QTV were analyzed by a fast Fourier and/or a wavelet transform algorithm. Zatebradine, an I_f channel blocker, had no significant effect on HRV and QTV. Diltiazem, a non-dihydropyridine I_CaL blocker, increased high frequency (HF) power and decreased the power ratio of the low frequency (LF) range to the HF range (L/H) in HRV, and increased QTV. Propranolol, a non-selective β-antagonist, decreased LF power and L/H ratios in HRV, and appreciably reduced QTV. These differences in pharmacological action may help us better understand the antiarrhythmic and/or proarrhythmic actions of these agents when they are used clinically for reducing HR.

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“…In einer anderen Studie wirkte Zatebradin zwar während der Ischämie antiarrhythmisch, verhinderte allerdings die ventrikulären Arrhythmien während der Reperfusion nicht [134]. Während adrenalininduzierte ventrikuläre Arrhythmien durch Zatebradin nicht vermindert wurden, kam es bei ouabaininduzierten Arrhythmien zu einem dosisabhängigen Rückgang der Arrhythmien [50]. Ventrikuläre Tachykardien, die sich durch das trizyklische Antidepressivum Amitriptylin hervorrufen lassen, ließen sich durch Zatebradin verhindern [4].…”

Section: In-situ-herzenunclassified

Selektive If-Kanal-Hemmung: eine Alternative in der Behandlung der koronaren Herzkrankheit?

Schipke

Büter

Hohlfeld

et al. 2006

Herz

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Several clinical studies demonstrate the importance of the heart rate for the cardiovascular morbidity and mortality. Over the last 50 years, some thought has been given to those substances that selectively reduce the heart rate. It is now recognized that I(f) ion channels of the sinus node play a major role in the automatism and modulation of the heart rate. Substances that selectively reduce the heart rate should decrease myocardial oxygen consumption and increase oxygen delivery via the prolonged diastolic coronary perfusion. Direct inotropic effects, however, are unlikely. In principle, anti-anginal and anti-ischemic effects of specific bradycardic substances can be expected. The clinical experience with some of the former bradycardic substances has not been sufficiently convincing. The more recent ivabradine (Procoralan presents an exception to this, as it successfully completed a clinical program for the treatment of chronically stable angina pectoris. In this review article, specific bradycardic substances (= I(f) channel inhibitors) are presented together with the corresponding experimental and clinical studies. The studies were selected against the background of the efficacy of I(f) channel inhibitors in the therapy of cardiovascular disease. As only ivabradine has completed a study on 5,000 patients, the discussion on that particular I(f) channel inhibitor is somewhat extensive. In addition, prospective possibilities and limitations of bradycardic substances are presented.

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Effects of zatebradine on ouabain-, two-stage coronary ligation- and epinephrine-induced ventricular tachyarrhythmias

Cited by 9 publications

References 28 publications

Arrhythmia Models for Drug Research: Classification of Antiarrhythmic Drugs

Arrhythmia Models for Drug Research: Classification of Antiarrhythmic Drugs

Three Different Bradycardic Agents, Zatebradine, Diltiazem and Propranolol, Distinctly Modify Heart Rate Variability and QT-Interval Variability

Selektive If-Kanal-Hemmung: eine Alternative in der Behandlung der koronaren Herzkrankheit?

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