Effects of dauricine,quinidine,and sotalol on action potential duration of papillary muscles in vitro

目的：观察蝙蝠葛碱对豚鼠乳头状肌的动作电位是否具有使用依赖性特征，并与奎尼丁、索他洛尔作平行比较．方法：利用细胞内微电极技术记录豚鼠乳头状肌跨膜动作电位．结果：蝙蝠葛碱２０μｍｏｌ·Ｌ－１能明显延长乳头状肌跨膜动作电位时程，在刺激周长为２００，３００，４００，６００，８００，１０００，２０００ｍｓ时，其延长动作电位时程的百分率分别为２２±８，１１±６，９±５，７±５，６±３，４３±２８，４５±２８，蝙蝠葛碱延长动作电位时程作用于刺激周期较短时作用明显，呈使用依赖性特征．而奎尼丁１μｍｏｌ·Ｌ－１和索他洛尔１０μｍｏｌ·Ｌ－１延长动作电位时程作用随刺激周期延长而增强，呈现逆向使用依赖性特征．结论：蝙蝠葛碱使用依赖性延长豚鼠乳头状肌动作电位时程．     

On the neuromuscular effects of pindolol and sotalol in the rat

The effects of pindolol and sotalol on neuromuscular transmission were tested using intracellular micro-electrode recording of resting membrane potentials, miniature end-plate potentials and end-plate potentials, and recording of muscle contractions upon nerve stimulation of rat phrenic nerve-hemidiaphragm preparations. Both pindolol and sotalol reduced the amplitudes of miniature end-plate potentials and end-plate potentials in a dose-dependent manner without significantly affecting their time-courses. Pindolol, but not sotalol, also increased the frequency of the miniature end-plate potentials and decreased the number of acetylcholine quanta released by nerve impulses. Neither of the drugs significantly affected resting membrane potentials of the muscle fibres or excitability of the motor nerve to electric stimulation.     

Efficacy and Mechanism of Intravenous Sotalol for Termination of Paroxysmal Supraventricular Tachycardia

ＳＶＴ ,ｉｎｃｌｕｄｉｎｇＡＶＲＴａｎｄＡＶＮＲＴ ,ｉｓａｋｉｎｄｏｆａｒｒｈｙｔｈｍｉａｏｆｔｅｎｓｅｅｎｉｎｃｌｉｎｉｃａｌｐｒａｃ ｔｉｃｅ .Ｓｏｔａｌｏｌ,ａｃｌａｓｓⅢａｎｔｉ ａｒｒｈｙｔｈｍｉｃｄｒｕｇｗｉｔｈａｄｄｉｔｉｏｎａｌβ ｂｌｏｃｋｉｎｇａｇｅｎｔｐｒｏｐｅｒｔｉｅｓ ,ｈａｓｂｅｅｎｗｉｄｅｌｙｕｓｅｄｔｏｔｒｅａｔｖａｒｉｏｕｓａｒｒｈｙｔｈｍｉａ(ｓｕｐｒａ ｖｅｎｔｒｉｃｕｌａｒａｎｄｖｅｎｔｒｉｃｕｌａｒ)ｅｆｆｉｃｉｅｎｔｌｙｉｎｗｅｓｔｅｒｎｃｏｕｎｔｒｉｅｓ[1 9]…     

Binding ofβ-adrenoceptor blocking drugs to human serum albumin,to α1-acid glycoprotein and to human serum

Summary The binding of 8 -adrenergic blocking drugs to human serum albumin, to ₁-acid glycoprotein and to serum from normal volunteers and from patients with rheumatoid arthritis was studied. Protein binding was determined in vitro using equilibrium dialysis of labelled drug at 25° C. Oxprenolol and propranolol were highly bound to serum, alprenolol, pindolol and timolol to a lesser degree, and atenolol, metoprolol and sotalol were negligibly bound. For the five compounds which were appreciably bound, the mean binding was significantly higher in serum from patients with rheumatoid arthritis than in serum from normal volunteers. For those drugs, binding to ₁-acid glycoprotein was higher than to human serum albumin, and binding to a mixture of both proteins approached that to serum from healthy volunteers. For each of these drugs there was a strong correlation between the serum ₁-glycoprotein concentration and the percentage binding.     

盐酸索他洛尔合成工艺条件的分析与优化

本文利用正交实验方法系统地研究了合成盐酸索他洛尔过程中各工艺参数对产品收率的影响 ,得到了最佳工艺条件 ,在此条件下 ,盐酸索他洛尔的收率可达 80 %以上     

Low dose amiodarone and sotalol in the treatment of recurrent, symptomatic atrial fibrillation: a comparative, placebo controlled study

OBJECTIVE—To assess and compare the safety and efficacy of amiodarone and sotalol in the treatment of patients with recurrent symptomatic atrial fibrillation.
DESIGN—Prospective, randomised, single blind, placebo controlled study.
SETTING—Tertiary cardiac referral centre.
PATIENTS—186 consecutive patients (97 men, 89 women; mean (SD) age, 63 (10) years) with recurrent, symptomatic atrial fibrillation.
INTERVENTIONS—65 patients were randomised to amiodarone, 61 to sotalol, and 60 to placebo. Patients receiving amiodarone were maintained at a dose of 200 mg/day after a 30 day loading phase. The sotalol dose was 160-480 mg daily, as tolerated.
MAIN OUTCOME MEASURES—Recurrence of atrial fibrillation or side effects.
RESULTS—In the amiodarone group, 31 of the 65 patients developed atrial fibrillation after an average of six months, while 15 (11 in sinus rhythm and four in atrial fibrillation) experienced significant side effects after an average of 16 months. In the sotalol group, relapse to atrial fibrillation occurred in 47 of the 61 patients after an average of eight months; three experienced side effects during the titration phase. In the placebo group, 53 of the 60 patients developed atrial fibrillation after an average of four months (p < 0.001 for amiodarone and sotalol v placebo; p < 0.001 for amiodarone v sotalol).
CONCLUSIONS—Both amiodarone and sotalol can be used for the maintenance of normal sinus rhythm in patients with symptomatic atrial fibrillation. Amiodarone is more effective but causes more side effects.


Keywords: amiodarone; sotalol; atrial fibrillation     

Detection of QTc interval prolongation using jacket telemetry in conscious non-human primates: comparison with implanted telemetry

Background and Purpose: During repeat-dose toxicity studies, ECGs are collected from chemically or physically-restrained animals over a short timeframe. This is problematic due to cardiovascular changes caused by manual restraint stress and anesthesia, and limited ECG sampling. These factors confound data interpretation, but may be overcome by using a non-invasive jacket-based ECG collection (JET). The current study investigated whether a jacketed external telemetry system could detect changes in cardiac intervals and heart rate in non-human primates (NHPs), previously implanted with a PCT transmitter.Experimental Approach: Twelve male cynomolgus monkeys were treated weekly with vehicle or sotalol (8, 16, 32 mg kg⁻¹) p.o. ECGs were collected continuously for 24 hours, following treatment, over 4 weeks. A satellite group of six NHPs was used for sotalol toxicokinetics.Key Results: Sotalol attained C_max values 1–3 hours after dosing, and exhibited dose-proportional exposure. In jacketed NHPs, sotalol dose-dependently increased QT/QTc intervals, prolonged PR interval, and reduced heart rate. Significant QTc prolongation of 27, 54 and 76 msec was detected by JET after 8, 16, and 32 mg kg⁻¹ sotalol, respectively, compared with time-matched vehicle-treated animals. Overall, JET-derived PR, QT, QTc intervals, QRS duration, and heart rate correlated well with those derived from PCT.Conclusions and Implications: The current findings clearly support the use of JET to quantify cardiac interval and rhythm changes, capable of detecting QTc prolongation caused by sotalol. JET may be a preferred method compared to restraint-based ECG because high-density ECG sampling can be collected in unstressed conscious monkeys, over several weeks.     

A comparison of sotalol and procainamide in symptomatic ventricular tachycardia

Summary The effects of oral sotalol were compared with 1000 and 1500 mg of procainamide in 23 patients with sustained ventricular tachycardia. The predictive value of an induction study after procainamide was assessed. The mean age of the study group was 62±12 years, and the mean ejection fraction was 32±16%. The cycle length (CL) of the induced tachycardia, the coupling interval (CI) of the first extrastimulus (in ms), and the number of noninducible (NI) patients are given in the table below. One patient developed torsades during the loading period of sotalol and is included in the number requiring cardioversion (DC). Important proarrhythmic effects (spontaneous occurrence of tachycardia) were seen twice after procainamide. Induction suppression by procainamide predicted success with sotalol (p=0.0013).Conclusion: Ventricular tachycardia seems to be less often inducible after oral sotalol than after procainamide. The success of procainamide during programmed electrical stimulation predicts the same for sotalol. If ventricular tachycardia remains inducible after oral sotalol, it is faster than after procainamide but slower than the baseline tachycardia. Both drugs slightly prolong refractoriness.