Disease relevance of AZIMILIDE

• OBJECTIVES: The purpose of this study was to assess the effect of oral azimilide dihydrochloride (AZ) 100 mg versus placebo on the onset, termination, and prevalence of atrial fibrillation (AF) in a subpopulation of patients in the Azimilide Postinfarct Survival Evaluation (ALIVE) trial [1].
• CONCLUSIONS: Azimilide dihydrochloride may be a safe and effective drug for reducing the frequency of VT and ventricular fibrillation in patients with implanted ICDs [2].
• Doses of 3, 10, and 30 mg/kg i.v. azimilide dihydrochloride were analyzed in 8 dogs in which sustained atrial flutter lasting more than 30 minutes was induced by burst pacing [3].
• INTRODUCTION: Azimilide (NE-10064) has antiarrhythmic and antifibrillatory effects in canine models of ventricular arrhythmia [4].
• Effects of azimilide dihydrochloride on circus movement atrial flutter in the canine sterile pericarditis model [3].

High impact information on AZIMILIDE

• Azimilide dihydrochloride was generally well tolerated and did not affect left ventricular ejection fraction or minimal energy requirements for defibrillation or pacing [2].
• Dual actions of the novel class III antiarrhythmic drug NE-10064 on delayed potassium channel currents in guinea pig ventricular and sinoatrial node cells [5].
• The purpose of this study was to assess the influence of multiple-dose oral administration of azimilide dihydrochloride on CYP2C19-mediated metabolism [6].
• Thus, no clinically important drug interactions are expected when azimilide dihydrochloride is coadministered with CYP3A4 inhibitors [7].
• Comparative oral bioavailability of azimilide dihydrochloride in the fed and fasted states [8].

Biological context of AZIMILIDE

• Azimilide (NE-10064) can prolong or shorten the action potential duration in canine ventricular myocytes: dependence on blockade of K, Ca, and Na channels [4].
• Pharmacokinetics and pharmacodynamics following intravenous doses of azimilide dihydrochloride [9].
• NE-10064 potently blocked the rapidly activating component of the delayed rectifier, IKr (IC50 0.4 microM), and inhibited IKs (IC50 3 microM) with nearly 10-fold less potency [10].

Anatomical context of AZIMILIDE

• Blockade of human IsK channels expressed in Xenopus oocytes by the novel class III antiarrhythmic NE-10064 [11].
• NE-10064 increased ventricular effective refractory period (VERP 166 +/- 5 ms predrug vs. 194 +/- 13 ms postdrug, p = 0.013), prolonged QTc interval (310 +/- 12 ms predrug vs. 350 +/- 16 ms postdrug, p = 0.004) and prolonged the effective refractory period (ERP) of noninfarcted myocardium (p = 0.045) [12].
• In ferret papillary muscles, NE-10064 increased effective refractory period (ERP) and decreased isometric twitch tension in a concentration-dependent manner (0.3-30 microM) [10].
• The class III antiarrhythmics azimilide dihydrochloride and dl-sotalol were evaluated for ability to suppress induction of ventricular tachyarrhythmias (VT) in anesthetized, male mongrel dogs 4-6 days after surgical infarction of the left ventricle (LV) produced by ligation/reperfusion of the left anterior descending coronary artery [13].

Associations of AZIMILIDE with other chemical compounds

• Comparison of the rate-dependent properties of the class III antiarrhythmic agents azimilide (NE-10064) and E-4031: considerations on the mechanism of reverse rate-dependent action potential prolongation [14].
• The novel class III antiarrhythmics NE-10064 and NE-10133 inhibit IsK channels expressed in Xenopus oocytes and IKs in guinea pig cardiac myocytes [15].

Analytical, diagnostic and therapeutic context of AZIMILIDE

• OBJECTIVES: This study evaluated the effects of azimilide dihydrochloride (AZ) on anti-tachycardia pacing (ATP) and shock-terminated events in patients with implantable cardioverter defibrillators (ICDs) [2].
• Azimilide dihydrochloride was investigated as adjunctive treatment for reducing the frequency of VT and, thus, the need for ICD therapies, including ATP and cardioversion/defibrillation (ICD shocks) in patients with inducible monomorphic VT [2].
• Azimilide dihydrochloride (75-125 mg/day) is currently being developed for use in prolonging the time to recurrence of atrial fibrillation/flutter and for reducing the frequency of shocks in patients with an implantable cardioverting defibrillator [16].
• On-line Raman spectroscopy was used to evaluate the effect of blending time on low dose, 1%, blend uniformity of azimilide dihydrochloride [17].
• Azimilide dihydrochloride (or azimilide) is a class III antiarrhythmic drug currently under investigation that has been tested in atrial fibrillation in four randomized, placebo-controlled clinical trials to assess efficacy and dose range [18].

References