Disease relevance of Ambasilide

• In an additional 6 dogs with sterile pericarditis and inducible AF, ambasilide prevented AF induction in all 6 [1].
• Class III antiarrhythmic drug action in experimental atrial fibrillation. Differences in reverse use dependence and effectiveness between d-sotalol and the new antiarrhythmic drug ambasilide [1].
• Effects of the potassium channel blocking agent ambasilide on ventricular arrhythmias induced by acute myocardial ischemia and sympathetic activation [2].
• We assessed the effects of ambasilide, 5 mg/kg intravenous (i.v.) bolus plus 5 mg.kg-1.hr-1 i.v. infusion, in 16 anesthetized cats in which ventricular arrhythmias could be induced reproducibly by the combination of acute myocardial ischemia and increased sympathetic activity [2].
• Ambasilide prevented nonsustained ventricular tachycardia in 2 (40%) of 5 animals [2].

High impact information on Ambasilide

• This study evaluated effects of ambasilide, quinidine, flecainide and verapamil on I(Kur.d) in isolated canine atrial myocytes [3].
• By comparison, ambasilide inhibited HERG channels with lower potency (IC(50) 3.6 microM), in a voltage- and time-dependent but frequency-independent manner (0.03-1 Hz) [4].
• The 50% inhibitory concentration of ambasilide averaged 23 +/- 2 microM and 34 +/- 3 microM for I(to) and I(Kur) respectively [5].
• Ambasilide (1 microM) prolonged the action potential (APD) at 20, 50 and 90% repolarization by 11.2 +/- 4.3, 13.8 +/- 3.9 and 13.6 +/- 3.7%, respectively, compared to control (n = 10) [6].
• The block of Ik by ambasilide was compared to that by E-4031 (5 microM), a putative selective blocker of that fast, inwardly rectifying component of Ik identified in guinea pig ventricle [6].

Biological context of Ambasilide

• The antiarrhythmic effect of ambasilide persisted when heart rate was kept constant by atrial pacing [2].
• Ambasilide decreased heart rate and blood pressure and prolonged QRS duration (26%, p < 0.05), QTc (17%, p < 0.0001), and JTc (16%, p < 0.005) [2].
• These data suggest that ambasilide, in addition to its Class III antiarrhythmic action, which is presumably due to its inhibitory effect on the delayed rectifier potassium current, possesses I/B type antiarrhythmic properties as a result of the inhibition of the fast sodium channels at high frequency rate with relatively fast kinetics [7].

Anatomical context of Ambasilide

• In Purkinje fibers, the prolonging effect of ambasilide on APD-80 was more pronounced at lower stimulation frequency, whereas APD-20 shortened at all stimulation frequencies [8].
• Electrophysiologic effects of ambasilide (LU 47110), a novel class III antiarrhythmic agent, on the properties of isolated rabbit and canine cardiac muscle [8].

Associations of Ambasilide with other chemical compounds

• We conclude that neither d-sotalol nor E-4031 affects I(to) or I(Kur), whereas ambasilide produces efficacious open-channel block of both currents, in human atrial myocytes [5].
• The action potential prolonging effect of dofetilide was reduced in the presence of increasing concentrations of isoproterenol whereas the effect of ambasilide was much less reduced [9].

Analytical, diagnostic and therapeutic context of Ambasilide

• The actions of ambasilide (LU-47110) on the action potential and membrane currents of isolated guinea pig ventricular myocytes were studied using voltage clamp techniques [6].
• Ventricular fibrillation was observed in 7 animals and never occurred after ambasilide (p < 0.001); however, 4 (57%) of these cats had sustained ventricular tachycardia requiring cardiac massage [2].
• We recorded transmembrane action potential (TAP) characteristics at different stimulation frequencies (0.5, 1, 1.5, and 2 Hz) and with different dosages of ambasilide (1, 10, and 50 microM) by using conventional microelectrode techniques [10].

References