The pharmacology of iprindole,a new antidepressant

Summary Iprindole, a tricyclic indole antidepressant shares in common with imipramine-type antidepressants the ability to potentiate the central effects of amphetamine, and potentiate the peripheral effects of direct acting catecholamines. In contrast to imipramine-type compounds iprindole does not inhibit H³NE uptake centrally or peripherally, does not block the peripheral actions of indirect acting sympathomimetic amines nor block the inhibiting effects of guanethidine on the vas deferens preparation. These findings suggest that iprindole enhances activity of adrenergic receptors through a mechanism unrelated to inhibition of reuptake of norepinephrine.The minimal anticholinergic and antihistaminic activity of iprindole supports the contention that these effects are unnecessary for antidepressant activity.Tests involving potentiation of amphetamine proved to be more predictive of the antidepressant activity of iprindole than tests involving reserpine antagonism.     

Efficacy of the latest fluoroquinolones against experimental Yersinia pestis

The efficacies of prophylactic and therapeutic gatifloxacin and moxifloxacin were assessed in a BALB/c mouse model of systemic and pneumonic plague and compared with ciprofloxacin. Mice were given 100 mg/kg of the antibiotic by oral administration twice daily for 7 days starting 1 h prior to infection or following infection. All antibiotics offered full protection for up to 6 h following systemic challenge, and for up to 30 h following an aerosol challenge. The efficacy of each of the antibiotics decreased when antibiotics were started 18 h following systemic challenge and 48 h following aerosol challenge. Fluoroquinolones may therefore be considered useful candidates for the treatment of bubonic and pneumonic plague.     

Incidence of cardiac arrhythmias during antidepressant therapy with maprotiline or nomifensine

In a prospective randomized study we searched for arrhythmogenic effects of the tetracyclic antidepressant, a maprotiline, and the tetrahydroisoquinoline derivative, nomifensine. Forty depressive patients from the psychiatric outpatients department were included in the study. Twenty patients in each group received maprotiline or nomifensine over three weeks in the recommended daily dosage of 75 mg. Rhythm analysis was performed before therapy, at the end of 3 weeks therapy, and 1 week after withdrawal from medication using a dual channel long-term ECG with monitoring periods of 10 h during normal daily activities. Before treatment, spontaneous incidence of all ventricular ectopics and of their complex forms was within the normal range when compared with ectopic activity of 121 "normal subjects" without detectable heart disease. No significant increase could be demonstrated during therapy with maprotiline or nomifensine, nor was any change observed 1 week after medication had been stopped. The same was true for supraventricular extrasystoles; atrial tachycardia, atrial flutter, and fibrillation were never seen. Sinoatrial (n=2) and atrioventricular block (n=1) were rare findings independent of and not affected by treatment. No bundle branch blocks were observed before, during, and after treatment. In contrast, despite the conservative dosage of both drugs, a therapy-dependent increase in average heart rate was found (p less than 0.001). This increase was significantly higher in patients receiving nomifensine than in those treated with maprotiline (p less than 0.001), suggesting a lower intrinsic anticholinergic activity of the latter compound.     

Effect of tetrodotoxin on experimental arrhythmias

Effects of tetrodotoxin (TTX) on the ventricular fibrillation threshold (VFT) in dogs and on various types of arrhythmias in cats were studied. TTX, 2–4 μg/kg i.v., raises VFT in dogs. TTX, 2–4 μg/kg i.v., suppressed Deslanoside- or aconitine-induced arrhythmias, and those induced by bilateral carotid occlusion or by electrical stimulation of the posterior hypothalamus in cats, but the effects are transient. TTX may exert its anti-arrhythmic effect in situ by acting on myocardium and nerve axons.     

Effect of diuretics on the course of experimental arrhythmias

The protective effect of triamterene was demonstrated on aconitine (rats) and strophanthin (cats) models of arrhythmias. Furosemide potentiates the antiarrhythmic effects of calcium chloride (rats) and strophanthin, ethacrynic acid potentiates the arrhythmogenic action of all agents used.     

卡维地洛抗实验性心律失常作用

目的　评价卡维地洛（ＣＶＤ）抗实验性心律失常作用,并与β受体阻断剂普萘洛尔（ＰＲＯ） 进行比较。方法　采用氯仿致小鼠室颤（ＶＦ） , 哇巴因、乌头碱致豚鼠、大鼠心律失常,肾上腺素致豚鼠心律失常, 以及结扎大鼠冠状动脉诱发心律失常等５ 种模型。结果　与溶媒对照组相比, ＣＶＤ１ ｍｇ·ｋｇ－１ 显著降低氯仿诱发的小鼠ＶＦ 发生率〔１８－７５ ％（３／１６） ｖｓ８１－２５％ （１３／１６）,Ｐ＜ ０－０１〕,此作用与ＰＲＯ 相似。１ ｍｇ·ｋｇ－１ ＣＶＤ 和ＰＲＯ 均显著提高致室早（ＶＥ） , 室速（ＶＴ）, ＶＦ, 心搏停止（ＣＡ） 所需哇巴因和乌头碱用量（ Ｐ＜０－０１ ｖｓ 溶剂对照组） ;ＣＶＤ 对抗哇巴因的致心律失常作用较等剂量ＰＲＯ 显著（ Ｐ＜ ０－０１ ,ＣＶＤ ｖｓ ＰＲＯ）。ＣＶＤ 剂量依赖性地显著缩短ｉｖ 肾上腺素４０ μｇ·ｋｇ－ １ 所致心律失常持续时间,有效减少结扎冠脉诱发的缺血性心律失常ＶＴ,ＶＦ,ＣＡ 的发生率并缩短ＶＴ 的持续时间。结论　ＣＶＤ 具有抗多种实验性心律失常作用,该作用在等剂量时至少与ＰＲＯ 相近,或强于ＰＲＯ。ＣＶＤ的这种作用最终将有益于接受其治疗的原发性高血压、冠心病、充血性心力衰竭患者     

Effect of alinidine on experimental cardiac arrhythmias

Alinidine (2.9 +/- 0.7 mg/kg) prevented an adrenaline-induced ventricular arrhythmia in dogs respired with halothane. In ouabain-induced ventricular tachycardia, a cumulative dose of alinidine (15.5 mg/kg) reduced the number of ventricular beats by 91.6 +/- 1.9%. The drug was much less effective in abolishing the ventricular tachycardia 24 h after ligation of a coronary artery, with only a 36 +/- 15% reduction in ventricular ectopic beats after 15.5 mg/kg. The administration of alinidine (0.5-1.0 mg/kg) to anaesthetized dogs with no cardiac arrhythmia reduced sinus node rate with little effect on the response of the node to vagal stimulation.     

阿魏酸钠抗实验性心律失常的作用

目的　探讨阿魏酸钠抗实验性心律失常的机制。方法　应用各种心律失常动物模型观察药物对实验性心律失常的作用。结果　阿魏酸钠 0 6 g·kg-1iv可对抗哇巴因、肾上腺素诱发的室性心律失常 (P <0 0 1) ,亦可对抗心肌缺血诱发的心律失常 (P <0 0 5 ) ,但不能拮抗乌头碱所诱发的心律失常 (P >0 0 5 )。结论　阿魏酸钠具有抗多种实验性心律失常的作用 ,其机制可能与钾离子通道及 β受体的阻断作用有关     

The effects of bisaramil on experimental arrhythmias

Antiarrhythmic activity of bisaramil (3-methyl,7-ethyl,9 alpha, 4'-(Cl-benzoyloxy)-3,7-diazabicyclo[3.3.1.]nonane monohydrochloride) was investigated in a variety of experimental arrhythmic models. Bisaramil at the dose range of 0.1-2 mg/kg given i.v. was able to protect against either chemically induced (chloroform, aconitine, adrenaline, ouabain) or coronary-ligation-induced arrhythmias. Bisaramil dose dependently increased fibrillation threshold both in the right auricle and in the right ventricle (ED50 approximately 0.2 mg/kg i.v.) and decreased the susceptibility of the heart to arrhythmias induced by programmed electrostimulation alone or together with local cooling of the heart. Bisaramil given orally (5-20 mg/kg) also showed antiarrhythmic activity with a medium (2-4 h) duration of the action. Therapeutic index of bisaramil was found to be 19.6 (rat); 5.0 (dog) by i.v. administration and 46.5 (rat); 15.5 (dog) by p.o. administration. This means that bisaramil may be given rather safely.     

Efficacy of intravenous disopyramide in acute cardiac arrhythmias

Summary The efficacy of intravenous disopyramide was studied during 200 episodes of supraventricular and ventricular arrhythmias in 160 patients, mainly presenting with acute myocardial infarction or cardiac failure. Disopyramide 50 mg was administered in a few seconds and any remaining dose within 2 to 5 min. The overall success rate was 80.5%. Intravenous disopyramide was more effective in patients with ventricular arrhythmias (85%) than in those with supraventricular arrhythmias (76%). Dose dependent prolongation of the PR interval, QRS time and the QT interval occurred in 16.32 and 20% of the cases, respectively. The adverse effects were aggravation of the arrhythmias, decrease of blood pressure and anticholinergic activity.     

Efficacy of verapamil against ventricular arrhythmias induced by programmed electrical stimulation in the late myocardial infarction phase in dogs.

The aim of the present study was to investigate the antiarrhythmic potential of verapamil in the late myocardial infarction period in conscious dogs. Verapamil was administered in cumulative doses (0.3 + 0.3 mg kg-1). The drug significantly lowered systolic and diastolic blood pressure after both doses. ECG signals showed short-lasting significant decrease in RR and QT intervals together with an increase in QTc interval. The parameters of the atrioventricular conduction system (PQ interval, 2:1 AV-conduction point) were significantly prolonged over the entire observation period. Ventricular effective refractory periods remained unaltered. In contrast to results obtained during acute ischaemia and in the first week thereafter, the present study demonstrates that verapamil moderately increases intraventricular conduction time 14 days after acute myocardial infarction. Verapamil prevented the induction of arrhythmias by programmed electrical stimulation (PES) in only 11% of all induction attempts. The lack of lengthening of refractory periods in the presence of a prolongation of intraventricular conduction time may be responsible for the poor antiarrhythmic efficacy. We conclude that verapamil is only of negligible value for the management of PES-induced ventricular arrhythmias in the late myocardial infarction period.     

磷酸喹哌抗实验性心律失常作用

磷酸喹哌(PQP)9mg·kg~(-1)iv明显降低小鼠室颤的死亡率;PQP 18mg·kg~(-1)ip对氯仿诱发小鼠室颤具有保护作用;PQP 6.3mg·kg~(-1)ip显著增加恒速(10mg·L~(-1)·min~(-1)滴注乌头碱引起麻醉大鼠室性早搏(VE)、室性心动过速(VT)、室性纤颤(VF)所需的乌头碱用量;PQP5.4 mg·kg~(-1)iv显著增加恒速(50mg·L~(-1)·min~(-1))滴注哇巴因引起麻醉豚鼠VE、VT和VF所需哇巴因用量;PQP3.36mg·kg~(-1)iv明显缩短肾上腺素诱发家兔室性心律失常的持续时间.结果表明PQP具有抗心律失常作用。小鼠PQPLD_(50)iv为93.33 mg·kg~(-1)。     

IQ_(23)抗实验性心律失常作用及其机制

IQ23为双苄基异喹啉类化合物,本实验观察IQ23对哇巴因所致豚鼠心律失常及离体心房的收缩性、自律性及功能性不应期(FRP)的作用,初步探讨IQ23抗实验性心律失常的机制。1材料与方法1.1药品IQ23由中国药科大学提供,纯度>99%。哇巴因,卡巴胆碱,肾上腺素,普萘洛尔购于Sigma公司,其余为国产分析纯。1.2哇巴因所致豚鼠心律失常模型的建立豚鼠20只,♀♂不拘,(280±20)g,华中科技大学同济医学院实验动物部提供,随机分为对照组(iv生理盐水1ml·kg-1)和实验组(iv0·5%IQ235mg·kg-1),10min后以0·19ml·min-1恒速静脉灌注0·003%哇巴因,记录出现…     

左旋体盐酸非洛普的抗实验性心律失常作用

目的　研究左旋体盐酸非洛普 [levo 1 (2 ,6 二甲基苯氧基 ) 2 (3 ,4 二甲氧基苯乙氨基 )丙烷盐酸盐 ,l DDPH对实验性心律失常的抑制作用。方法　iv哇巴因、乌头碱或氯化钙制造大鼠、豚鼠室性心律失常模型 ;标准微电极技术记录动作电位 ;全细胞膜片钳技术记录L型钙电流 (ICa,L)。结果　l DDPH 5 0mg·kg-1抑制哇巴因诱发的豚鼠室性心律失常以及乌头碱和氯化钙诱发的大鼠室性心律失常 ;l DDPH 3 0 μmol·L-1缩短豚鼠右心室乳头肌细胞 5 0 %动作电位时程 (APD50 )并延长有效不应期 (ERP) (n =6,P <0 0 5 ) ;l DDPH抑制单个豚鼠心室肌细胞ICa,L,其IC50 值为 12 9(95 %可信限 :7 0～ 18 8) μmol·L-1(n =5 )。结论　l DDPH具有抗实验性心律失常作用 ;其机制与抑制ICa,L、缩短APD50 并延长ERP有关