Disease relevance of N-(2-diethylaminoethyl)-4-methanesulfonamido-benzamide

• The antiarrhythmic and electrophysiologic profiles of sematilide, a "pure" class III agent, were determined in 27 patients with clinical ventricular arrhythmias and inducible sustained ventricular tachycardia during electrophysiologic study [1].
• The right ventricular effective refractory period (at 600 ms) increased by 38 +/- 14 ms in patients whose sustained ventricular tachycardia was suppressed by sematilide and by 19 +/- 18 ms in patients not suppressed (P = .015) [1].
• Eight patients were placed on long-term sematilide therapy, and during a mean follow-up period of 7.0 +/- 7.5 months, two patients developed sudden cardiac death, and one additional patient had recurrent sustained ventricular tachycardia [1].
• Hemodynamic effects of intravenous sematilide in patients with congestive heart failure: a class III antiarrhythmic agent without cardiodepressant effects [2].
• Pharmacokinetics of sematilide in renal failure [3].

High impact information on N-(2-diethylaminoethyl)-4-methanesulfonamido-benzamide

• Both low (n = 20) and high (n = 19) dose sematilide infusions produced dose-dependent increases in QT interval (5 +/- 8% [mean +/- SD] and 18 +/- 10%, respectively) and corrected QT interval (4 +/- 8% and 14 +/- 10%), and high dose sematilide decreased heart rate by 7 +/- 10% (all p < 0.025 vs. baseline) [2].
• Sematilide showed no adverse hemodynamic effects in patients with left ventricular ejection fraction < or = 25% or > 25% and in patients with cardiac index < 2 or > or = 2 liters/min per m2 [2].
• Rate-dependent effects of sematilide on action potential duration in isolated guinea pig ventricular myocytes [4].
• We examined the underlying mechanism for rate-dependent effects of sematilide on action potential duration (APD) in guinea pig ventricular myocytes [4].
• Glibenclamide and sematilide neither enhanced the post-ischemic recovery of left ventricular developed pressure nor affected cation changes during reperfusion [5].

Chemical compound and disease context of N-(2-diethylaminoethyl)-4-methanesulfonamido-benzamide

• Using canine ventricular arrhythmia models induced by two-stage coronary ligation, digitalis, adrenaline, coronary ligation and reperfusion, and programmed electrical stimulation (PES), we examined the antiarrhythmic or proarrhythmic effects of sematilide, N-[2(diethylamino)ethyl]-4-[(methylsulfonyl)amino]-benzamide hydrochloride [6].
• Comparison of the in vivo electrophysiological and proarrhythmic effects of amiodarone with those of a selective class III drug, sematilide, using a canine chronic atrioventricular block model [7].

Biological context of N-(2-diethylaminoethyl)-4-methanesulfonamido-benzamide

• All of these factors may contribute to reverse use-dependent effects on action potential prolongation by sematilide [4].
• A randomized, two-period, two-treatment study was conducted to investigate the effect of renal impairment on the pharmacokinetics of the Class III antiarrhythmic sematilide HCl [3].
• The bioavailability of sematilide was 0.47 (0.15) [8].
• Comparative kinetics of sematilide in four species [9].
• Application of 10, 30, 100 and 300 microM sematilide caused a concentration-dependent inhibition of the delayed rectifier K+ current (IC50 approx. 25 microM) [10].

Anatomical context of N-(2-diethylaminoethyl)-4-methanesulfonamido-benzamide

• The effects of sematilide, a novel class III antiarrhythmic agent, on membrane currents were examined in single myocytes isolated from the rabbit left atrium, using the whole-cell voltage clamp technique [10].
• In this study, we examined the in vitro effects of sematilide (1-100 microM) on isolated sinoatrial (SA) node, atrioventricular (AV) node, and atrial muscle [11].
• Our objective was to define the actions of sematilide in rabbits and to assess the contribution of the delayed rectifier (IK) to rate dependence of action potential duration (APD) in rabbit ventricular myocardium [12].
• These results strongly suggested that the neutral form of sematilide may penetrate the cardiac cell membrane via hydrophobic pathway [13].

Associations of N-(2-diethylaminoethyl)-4-methanesulfonamido-benzamide with other chemical compounds

• Based on the experimentally determined linear relationship between total clearance of sematilide and creatinine clearance, modified dose regimens for sematilide HCl in patients with renal impairment and functionally anephric patients off hemodialysis were developed [3].
• Electrophysiological effects of sematilide, a novel class III antiarrhythmic agent, were examined and compared with those of (+/-)sotalol in guinea pig left atrium by a conventional microelectrode technique [14].
• Amiodarone or sematilide (3 and 30 mg/kg; n=4 for each group) was administered orally without anesthesia under continuous ECG monitoring [7].

Gene context of N-(2-diethylaminoethyl)-4-methanesulfonamido-benzamide

• Sematilide blocks the inward rectifier potassium channel in isolated guinea pig ventricular myocytes [13].

Analytical, diagnostic and therapeutic context of N-(2-diethylaminoethyl)-4-methanesulfonamido-benzamide

• After treatment with oral sematilide (mean dose, 133 +/- 29 mg every 8 hours), the patients underwent repeat 24-hour ambulatory ECG monitoring and electrophysiologic study [1].
• Compounds 6a,d,f-k and 11 exhibited potency in the in vitro Purkinje fiber assay comparable to that of N-[2-(diethylamino)ethyl]-4- [(methylsulfonyl)amino]benzamide (1, sematilide), a potent selective class III agent which is undergoing clinical trials [15].
• Determination of sematilide in plasma by high-performance liquid chromatography [16].
• Separated by a 14-day washout period, the subjects received a constant rate intravenous infusion of 40 mg sematilide HCl over 30 minutes and a tablet containing 100 mg of the drug [3].
• The goals of this retrospective study with the novel class III antiarrhythmic sematilide HCI were to investigate: a) whether there existed interspecies correlations and b) whether reliable animal-to-human predictions were possible for the main pharmacokinetics parameters [9].

References