Disease relevance of Ersentilide

• During a subsequent exercise test, ersentilide prevented VF in 85% (11 of 13) of the high risk animals and showed no proarrhythmic effects in the 6 dogs without arrhythmias in the initial test [1].
• METHODS: Ersentilide was tested in 19 dogs with a healed myocardial infarction (MI) undergoing two minutes of circumflex artery occlusion (CAO) during sub-maximal treadmill exercise [1].
• Ersentilide lowered heart rate at all levels of exercise and during acute myocardial ischemia [1].
• Despite its ineffectiveness in preventing electrical induction of tachycardia, CK-3579 produced a significant increase in the cycle length of the induced ventricular rhythm [2].

High impact information on Ersentilide

• Ersentilide prolonged left ventricular monophasic action potential duration by 30% (from 179 +/- 6 ms to 233 +/- 5 ms, p < 0.001) at a 360 ms cycle length and completely prevented its shortening during sympathetic stimulation [1].
• Epicardial monophasic action potential duration was measured before and after ersentilide in 8 anesthetized open chest dogs at baseline and during stimulation of the left stellate ganglion at constant paced heart rate [1].
• The IC50 for CK-4001 at the beta 1-adrenoceptor was 38.1 +/- 8 microM and > 100 microM at the beta 2-adrenoceptor [3].
• Both CK-3579 and CK-4000 were equipotent in displacing [3H]dihydroalprenolol from cardiac membranes (IC50 = 2.4 +/- 0.3 and 1.7 +/- 0.4 microM, respectively) and were approximately 23-59 times more selective for the heart receptor than the lung receptor [3].
• We examined the beta 1- and beta 2-adrenoceptor binding properties, cellular electrophysiology, and antiarrhythmic efficacy of CK-3579 and the two enantiomers CK-4000 (S) and CK-4001 (R) [3].

Chemical compound and disease context of Ersentilide

• The antiarrhythmic and antifibrillatory actions of the CK-3579 and sematilide, two new class III antiarrhythmic drugs, administered in a multiple-dose regimen were evaluated in conscious dogs 3-5 days after anterior myocardial infarction [2].

Anatomical context of Ersentilide

• CK-4000 inhibits the potassium delayed rectifier current Ik in a concentration-dependent manner in isolated feline ventricular myocytes [3].

Analytical, diagnostic and therapeutic context of Ersentilide

• Sematilide significantly suppressed the induction of ventricular tachyarrhythmia by programmed electrical stimulation in six of 10 postinfarcted dogs, whereas CK-3579 suppressed the induction of tachyarrhythmia in only two of 10 animals [2].

References