cilobradine and Bradycardia

cilobradine has been researched along with Bradycardia* in 3 studies

Other Studies

3 other study(ies) available for cilobradine and Bradycardia

ArticleYear
Bradycardic and proarrhythmic properties of sinus node inhibitors.
    Molecular pharmacology, 2006, Volume: 69, Issue:4

    Sinus node inhibitors reduce the heart rate presumably by blocking the pacemaker current If in the cardiac conduction system. This pacemaker current is carried by four hyperpolarization-activated, cyclic nucleotide-gated cation (HCN) channels. We tested the potential subtype-specificity of the sinus node inhibitors cilobradine, ivabradine, and zatebradine using cloned HCN channels. All three substances blocked the slow inward current through human HCN1, HCN2, HCN3, and HCN4 channels. There was no subtype-specificity for the steady-state block, with mean IC50 values of 0.99, 2.25, and 1.96 microM for cilobradine, ivabradine, and zatebradine, respectively. Native If, recorded from mouse sinoatrial node cells, was slightly more efficiently blocked by cilobradine (IC50 value of 0.62 microM) than were the HCN currents. The block of I(f) in sinoatrial node cells resulted in slower and dysrhythmic spontaneous action potentials. The in vivo action of these blockers was analyzed using telemetric ECG recordings in mice. Each compound reduced the heart rate dose-dependently from 600 to 200 bpm with ED50 values of 1.2, 4.7, and 1.8 mg/kg for cilobradine, ivabradine, and zatebradine, respectively. beta-Adrenergic stimulation or forced physical activity only partly reversed this bradycardia. In addition to bradycardia, all three drugs induced increasing arrhythmia at concentrations greater than 5 mg/kg for cilobradine, greater than 10 mg/kg for zatebradine, or greater than 15 mg/kg for ivabradine. This dysrhythmic heart rate is characterized by periodic fluctuations of the duration between the T and P wave, resembling a form of sick sinus syndrome in humans. Hence, all available sinus node inhibitors possess an as-yet-unrecognized proarrhythmic potential.

    Topics: Animals; Arrhythmias, Cardiac; Benzazepines; Bradycardia; Cardiotonic Agents; Cloning, Molecular; Electrocardiography; Humans; Ivabradine; Mice; Mice, Inbred C57BL; Piperidines; Sinoatrial Node; Up-Regulation

2006
The impact of organic inhibitors of the hyperpolarization activated current (Ih) on the electroretinogram (ERG) of rodents.
    Archives italiennes de biologie, 2004, Volume: 142, Issue:2

    We have compared the effect of two distinct Ih inhibitors on the temporal properties of the ERG response that, as previously shown, correlates well with the HCN activation in rods. The present results confirm the notion that cilobradine is more effective than zatebradine in inducing bradycardia. Importantly, the doses of cilobradine that reduce the heart rate to values comparable to, or lower than, those obtained with higher doses of zatebradine have little effect on the frequency response of the ERG. While more potent than zatebradine in its bradycardic action, cilobradine appears comparatively less effective on the visual response. A possible explanation is that the affinity of cilobradine for the HCN channels in the heart is higher than that for the HCN channels of retinal neurons.

    Topics: Animals; Benzazepines; Bradycardia; Cardiotonic Agents; Dose-Response Relationship, Drug; Electroretinography; Heart; Heart Rate; Ion Channels; Membrane Potentials; Piperidines; Rats; Rats, Long-Evans; Retina; Retinal Ganglion Cells; Retinal Rod Photoreceptor Cells; Tachycardia

2004
Effects of a bradycardic agent on postischemic cardiac recovery in rabbits.
    Journal of physiology and pharmacology : an official journal of the Polish Physiological Society, 2004, Volume: 55, Issue:4

    Decreasing heart rate might be beneficial for improvement of myocardial energetics and could reduce the severity of myocardial ischemia. We examined the contribution of heart rate reduction by cilobradine (DK-AH 269), a direct sinus node inhibitor, on left ventricular function and peripheral vasomotion in anesthetized rabbits with experimental myocardial infarction. The rabbits were randomized to receive either placebo (n=10) or cilobradine (n=7). Cilobradine decreased significantly heart rate from 163 +/- 33 to 131 +/- 13 bpm, p< 0.05, without any inotopic or vascular effects. After 60 min coronary occlusion and 30 min reperfusion, both systolic and diastolic ventricular function were more reduced in the cilobradine group; i.e. maximal left ventricular pressure significantly decreased to 62 +/- 11 mmHg, p < 0.05 (placebo: 77 +/- 9 mmHg); dP/dt(min) significantly decreased to -904 +/- 247 mmHg, p < 0.05 (placebo: -1106 +/- 242 mmHg). However, infarct size in the cilobradine group was significantly smaller compared with the placebo group. In conclusion, cilobradine reduced heart rate without any negative inotropic effect and reduced infarct size. On that account, this bradycardic agent might open a promising therapeutical avenue to treat postischemic dysfunction.

    Topics: Animals; Benzazepines; Bradycardia; Heart Rate; Myocardial Ischemia; Piperidines; Rabbits

2004