Effects of tedisamil, atenolol and their combination on heart andrate‐dependent QT interval in healthy volunteers

Démolis, Jean-Louis; Martel, Christine; Funck‐Brentano, Christian; Sachse, Alisia; Weimann, H; Jaillon, Patrice

doi:10.1046/j.1365-2125.1997.t01-1-00603.x

Cited by 15 publications

(8 citation statements)

References 12 publications

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“…Although tedisamil does show a dose dependent bradycardic effect on coronary artery disease patients at rest,3 4 the effects are smaller during exercise 5. In the present study, reductions of 5–15 bpm were seen (unrelated to dose) during exercise, and these findings are consistent with the studies mentioned above.…”

Section: Discussionsupporting

confidence: 92%

Antianginal and anti-ischaemic efficacy of tedisamil, a potassium channel blocker

Fox

2000

Heart

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Objective-To determine the eYcacy and safety of the potassium channel blocker tedisamil versus placebo in the treatment of patients with stable angina. Design-Prospective, double blind, placebo controlled study. 203 patients first completed a seven day placebo run in. They were then randomised to receive 50 mg, 100 mg or 150 mg tedisamil twice daily, or placebo. Treadmill exercise testing was carried out at baseline and after 14 days of double blind treatment. Main outcome measures-Primary eYcacy parameters were an increase in total exercise duration and a reduction of the sum of ST segment depression using six ECG leads at maximum workload at trough (12 hours after last medication). Secondary aims included increase in exercise time to onset of 0.1 mV ST segment depression, increase in exercise time to onset of any anginal pain, and reduction in ST segment depression in any of the six specified leads at maximum workload. These were all at trough. The same parameters were also assessed at peak concentrations (two hours after administration). Overall attacks of angina and the use of short acting nitrates were assessed from patient diaries. Results-Tedisamil led to a dose dependent prolongation of exercise duration (significant at all concentrations), an eVect that was greater at peak than at trough. Treatment also led to a significant dose dependent reduction in the sum of ST segment depression at both trough and peak concentrations. Tedisamil also decreased (in a dose dependent way) the frequency of anginal attacks and the consumption of short acting nitrates, an improvement that became significant for all doses in the second treatment week. Adverse events with tedisamil were few. There was a pronounced rise in the incidence of diarrhoea with the 150 mg twice daily regimen. Bradycardic eVects and increases in QT interval were dose dependent, but were no more evident at exercise than at rest. Conclusions-Tedisamil, at doses of 50-100 mg twice daily, was found to be an eVective antianginal and anti-ischaemic agent. At doses above 100 mg twice daily its main side eVect, diarrhoea, becomes pronounced; therefore the 50-100 mg twice daily regimen appears to be appropriate.

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Section: Discussionsupporting

confidence: 92%

Antianginal and anti-ischaemic efficacy of tedisamil, a potassium channel blocker

Fox

2000

Heart

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“…[14][15][16][17] Additional recordings were obtained during the course of a submaximal exercise test performed on a bicycle ergometer (model EM840; Siemens, Paris, France). On each study day, subjects performed an exercise test 2 hours after telithromycin, clarithromycin, or placebo administration (ie, at the time of expected maximum telithromycinclarithromycin plasma concentration).…”

Section: Data Acquisitionmentioning

confidence: 99%

Effect of single and repeated oral doses of telithromycin on cardiac QT interval in healthy subjects

Démolis

Vacheron

Cardus

et al. 2003

Clin Pharma and Therapeutics

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“…However, tail‐cuff blood pressure measurements represent a significant stress to conscious animals and may therefore underestimate the bradycardic effect of tedisamil. Actually, during maximum exercise, tedisamil did not decrease heart rate in healthy men ( Demolis et al ., 1997 ).…”

Section: Discussionmentioning

confidence: 99%

Tedisamil attenuates foetal transformation of myosin in the hypertrophied rat myocardium

Turcani

Thormaehlen

Rupp

2004

British J Pharmacology

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1 Reduction in repolarizing potassium currents has controversial effects on hypertrophic responses in cardiomyocytes of transgenic models and cultured cardiomyocytes. It remains thus unknown whether a blockade of potassium channels with tedisamil (N,N 0 dicyclopropylmethylene-9,9-tetramethylene-3,7-diazabicyclo(3.3.1)nonane dihydrochloride) has any effects on cardiac growth during postnatal development or pressure overload. 2 To test the hypothesis that a treatment with tedisamil affects cardiac growth or protein phenotype, sham-operated rats and rats with ascending aorta constriction were treated with tedisamil (36 mg kg day À1 ) for 7 weeks. Left ventricular mass and geometry, relative expression of myosin isoforms, hydroxyproline concentration and isovolumic ventricular function were assessed. 3 Rats with aortic constriction exhibited a marked increase in left ventricular weight and the diastolic pressure-volume relationship was shifted to smaller volumes. The hydroxyproline concentration remained unaltered. The proportion of a-myosin heavy chains was, however, reduced (Po0.05). Hypertrophied left ventricles manifested an enhanced overall performance but depressed myocardial contractility. 4 Administration of tedisamil was associated with decreased heart rate (Po0.05). In contrast, cardiac growth in sham-operated rats and concentric left ventricular hypertrophy of pressureoverloaded animals was not significantly altered. Hypertrophied hearts from rats treated with tedisamil expressed more a-myosin heavy chains (6574 versus 5774%; Po0.05). Also, maximal rate of wall stress rise and decline was higher (Po0.05) in tedisamil-treated pressure-overloaded rats. 5 In the rat model of pressure-overloaded hypertrophy, tedisamil had no effect on cardiac growth but partially corrected myocardial dysfunction. Postulated mechanism of this effect is the phenotype modification of myosin filaments in hypertrophied myocardium. British Journal of Pharmacology (2004) 143, 561-572. doi:10.1038/sj.bjp.0705992 Keywords: Potassium channel inhibition; pressure overload; heart hypertrophy; myosin isoforms; ventricular performance; myocardial contractility; tedisamilAbbreviations: ANCOVA, analysis of covariance; C R , midwall circumference; I f , hyperpolarization-activated current; I K , delayed outward rectifying potassium currents; I to , calcium-independent transient outward current; P, left intraventricular pressure; 7dP/dt max , maximal rate of intraventricular pressure rise and decline; S, mean wall stress; 7dS/dt max , maximal rate of wall stress rise and decline; V, left ventricular cavity volume; W, left ventricular wall volume

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Effects of tedisamil, atenolol and their combination on heart andrate‐dependent QT interval in healthy volunteers

Cited by 15 publications

References 12 publications

Antianginal and anti-ischaemic efficacy of tedisamil, a potassium channel blocker

Antianginal and anti-ischaemic efficacy of tedisamil, a potassium channel blocker

Effect of single and repeated oral doses of telithromycin on cardiac QT interval in healthy subjects

Tedisamil attenuates foetal transformation of myosin in the hypertrophied rat myocardium

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