二(二甲氨基)-二苯甲烷的抗心律失常作用

碘杂环化合物(IHC-64,IHC-65,IHC-66)有抗心律失常、降血压,并表现钙拮抗效应。4,4′-二(二甲氨基)-二苯甲烷[4,4′-bis(dimethyl amino)-diphenyl methane,BDDM]是合成碘杂环化合物的前体物,与抗心律失常药利多卡因、安博律定(aprindine)等在化学结构上有相近之处,如苯环和碱性氨基。本实验观察了碘杂环前体物BDDM的抗实验性心律失常作用。并进一步探讨本系列合成物的构效关系。     

碘杂环化合物IHC-72抗实验性心律失常作用

碘杂环-72能提高哇巴因诱发豚鼠心律失常的用量;防治氯化钡、氯化钙导致的心律失常;对结扎冠脉诱发大鼠心律失常有明显预防作用;亦可降低氯仿引起小鼠室颤的发生率,并明显减慢麻醉大鼠的心率。碘杂环-72可能是通过钙拮抗效应而产生抗心律失常作用.     

对碘杂环64号药致突变作用的评价

<正> 碘杂环64号化学名为3,6-二[二甲氨基]-二苯骈碘杂环甲酸盐[3.6-di(dimethylamino)-dibenzopyriodonium formate,IHC-64]是兰州大学化学系黄文魁教授合成的一种新型化合物。该化合物具有降血压、抗心律失常、镇痛和降脂等药理效应。该药的亚急性试验已有报道,但长期应用IHC-64是否具有致突变作用迄今未见报道。为确保临床用药安全,根据新药审批办法规定,我们对IHC-64的致突变作用进行了实验研究。实验材料碘杂环64号由兰州大学化学系陈淑英教     

3,6-二[二甲氨基]-二苯骈碘杂环甲酸盐致畸、致突变检测

3,6-二[二甲氨基]-二苯骈碘杂环甲酸盐(HIC-64)是新合成的一种化合物,具有降血压、抗心律失常、镇痛和降血脂等药理效应。为了搞清其是否有致畸和致突变作用,我们对HIC-64致畸和致突变作用进行了检测,结果报道如下: 一、致畸试验 HIC-64由甘肃省药物研究所提供。临用前配成水溶液,避光保存备用。敌枯双粉剂由华西医科大学惠赠。     

碘杂环化合物对家兔缺血心肌兴奋阈和颤动阈的影响

前文报道,碘杂环化合物(3,6-二[二甲氨基]-二苯并碘因甲酸盐,以下简称IHC-64)对多种实验性心律失常有较好的防治效果,对离体豚鼠乳头肌具有负性肌力、降低自律性、延长有效不应期等作用,而不影响其兴奋性,即呈兴奋-收缩脱偶联的现象。为了探讨IHC-64在整体水平对缺血心肌的影响,本实验以家兔缺血心肌的心电图兴奋阈和颤动阈为指标,观察药物的作用。     

4′甲基-7-(2-羟基-3-异丙胺基丙氧基)黄酮盐酸盐的抗实验性心律失常作用

4'-甲基-7-(2-羟基-3-异丙胺基丙氧基)黄酮盐酸盐(SIPI-549)对乌头碱诱发的大鼠心律失常有预防作用,对氯化钡诱发的家兔心律失常有治疗作用,对哇巴因诱发的豚鼠心律失常则无明显作用。抗心律失常作用比普萘洛尔强,但比胺碘酮弱。对狗急性心肌梗塞后24 h 的心律失常,本品的抗心律失常作用比利多卡因弱,但负性频率作用比其为强。     

邻卤代苄基异喹啉碘盐抗心律失常作用的研究

目的：比较1-(邻-碘苄基)-6，7-甲二氧基-2-甲基-3，4-二氢异喹啉碘盐(O-BIMMDI)与1-(邻-溴苄基)-6，7-甲二氧基-2-甲基-3，4-二氢异喹啉碘盐(O-BBMMDI)，对实验性心律失常模型的影响。方法：采用乌头碱、氯化钡和结扎左冠状动脉前降支方法制备大鼠心律失常模型，观察并比较O-BIMMDI与O-BBMMDI的保护作用。结果：O-BIMMDI和O-BBMMDI可对抗乌头碱、氯化钡所致的大鼠心律失常，延长心律失常诱发时间，缩短心律失常持续时间；对结扎左冠状动脉前降支所诱发的大鼠心律失常也有一定的对抗作用，并可减轻结扎造成的心肌缺血。O-BBMMDI抗心律失常作用优于O-BBMMDI。结论：O-BBMMDI和O-BBMMDI均可对抗大鼠心律失常模型，而O-BBMMDI抗心律失常作用优于O-BBMMDI．     

13-正丙基巴马汀的抗心律失常作用

iv13—正丙基巴马汀(13—n—Ptopyl—Pal-matine)8mg·kg~(-1)能显著减少氯仿诱发小鼠室颤的发生率.提高哇巴因致豚鼠室早、室速、室颤及心搏停止的阈剂量。iv1、3 mg·kg~(-1)可明显减少CaCl_2诱发小鼠心律失常的发生率.缩短BaCl_2诱发大鼠心律失常的持续时间、但对乌头碱诱发大鼠心律失常无明显的对抗作用。此外,13—正丙基巴马汀还能明显提高大鼠心肌细胞膜Na~+,K~+—ATP酶的活性。     

3,6—二[二甲氨基]—二苯骈碘杂环甲酸盐对大鼠血脂和脂蛋白的影响

<正> 3,6—二[二甲氨基]—二苯骈碘杂环甲酸盐[3,6—di—(dimethylamino)—dibenzopyriodonium formate,简称IHC—64]经药理实验和临床初步观察表明其有降血压和降低血清胆固醇的作用。文献报道某些抗高血压药物(如利尿降压药、β受体阻滞剂和肾上腺素能神经阻断药等)对血脂和血脂蛋白可产生不利影响.IHC—64作为新型降压药,可降低血清胆固醇,对脂代谢究竟有何影响值得探讨。为此我们以大鼠为实验对象,探讨IHC—64对大鼠血脂和脂蛋白的影响。现将结果报告如下。1 给药7 d和14 d后对大鼠血清脂质的影响大鼠     

SIPI—644对乌头碱诱发大鼠室性心律失常的作用

用乌头碱诱发的大鼠室性心律失常模型观察了SIPI-644十二指肠给药(id)的抗心律失常作用。本品id 50,100和200 mg/kg,均能显著对抗乌头碱诱发的各种室性心律失常,但三个剂量组之间没有明显差异p>0.05),抗心律失常作用的强度和剂量没有明显相关性。其id的药效比iv的药效弱,它和胺碘酮、静注的ED_(50)分别为12.3和27.8mg/kg,它们约TI分别为11.7和5.3。     

烟浪丁的抗心律失常作用

NICO 100 mg/kg iv,可明显对抗乌头碱和BaCl₂诱发大鼠及氯仿-肾上腺素引起兔的心律失常;降低CaCl₂所致的大鼠室颤率;提高豚鼠心脏哇巴因中毒时的耐量。50 mg/kg iv,也可预防结扎大鼠左冠状动脉引起的心律失常。50～100 mg/kg ip,能降低氯仿或ACh—CaCl₂引起的小鼠室颤率或房颤(扑)率。NICO可减慢豚鼠心率,且可拮抗异丙肾上腺素的正性变率作用。     

葡甲胺环腺苷酸的抗心律失常作用

MCA iv 100 mg/kg可推迟肾上腺素诱发兔心律失常的潜伏期,缩短心律失常的持续时间;减少CaCl_2引起大鼠室速和室颤的发生率.MCA不能推迟乌头碱诱发大鼠室早的潜伏期,但可减少大鼠室速的发生率;对哇巴因引起的豚鼠心律失常无对抗作用.MCA iv 200 mg/kg可减慢急性缺氧大鼠的心率,增加心脏收缩幅度.     

Arrhythmias induced by myocardial ischaemia-reperfusion are sensitive to ionotropic excitatory amino acid receptor antagonists

We have investigated the effects of (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine hydrogen maleate (MK801), a non-competitive N-methyl-D-aspartate (NMDA) ionotropic excitatory amino acid receptor antagonist, and 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), a non-NMDA ionotropic excitatory amino acid receptor antagonist, ketamine and memantine, NMDA receptor channel blockers, on ventricular arrhythmias induced by myocardial ischaemia and myocardial ischaemia-reperfusion. Coronary artery occlusion caused 100 +/- 2% ventricular tachycardia, in saline treated group, and 60 +/- 3% ventricular fibrillation. 66 +/- 6% of the animals recovered from ventricular fibrillation, while in 34 +/- 4% of animals the ventricular fibrillation caused mortality. The incidence of ventricular tachycardia, ventricular fibrillation and mortality was not modified by treatment of rats with MK801 (0.3 mg/kg i.v.), CNQX (1 mg/kg i.v.), ketamine (10 mg/kg) and memantine (1.5 mg/kg), injected 5 min prior to occlusion. Reperfusion caused severe arrhythmias which started within 5 +/- 2 s. For instance, in the saline treated group, the incidence of ventricular tachycardia was 100 +/- 5%, while ventricular fibrillation occurred in 87 +/- 3% of the animals and lasted 90 +/- 12 s. The mortality was 62 +/- 6%. The incidence of ventricular tachycardia, ventricular fibrillation and mortality induced by reperfusion was greatly (P < 0.01) reduced in animals treated with MK801 (0.3 mg/kg i.v.), CNQX (1 mg/kg i.v.), ketamine (10 mg/kg) and memantine (1.5 mg/kg), injected 5 min prior to occlusion. Therefore, reperfusion-induced arrhythmias, but not ischaemia-induced arrhythmias, are sensitive to NMDA/non-NMDA ionotropic excitatory amino acid receptor antagonists.     

Suppression of ventricular arrhythmias resulting from acute coronary artery ligation in rat by imipramine

The potential antiarrhythmic activity of imipramine against ventricular arrhythmias induced by coronary artery ligation in rats has been investigated and compared with procainamide. Imipramide (1 and 5 mg/kg-1) or procainamide (5 and 10 mg/kg-1) or solvent were injected intravenously 30 min before ligation. Imipramine reduced the total number of ventricular ectopic beats as well as the incidence and duration of ventricular tachycardia and ventricular fibrillation. The drug did not significantly affect the blood pressure but reduced the heart rate. The antiarrhythmic activity of imipramine is postulated to be due to a quinidine-like effect and/or alpha-adrenergic blocking activity. The study confirms the potential utility of imipramine as an antiarrhythmic drug.     

硫酸锌对实验性心律失常的影响

用6种实验性心律失常动物模型,观察ZnSO_4的抗心律失常作用。ZnSO_4 iv10mg/kg能明显对抗乌头碱和BaCl_2诱发大鼠心律失常,显著缩短CHCl_3-肾上腺素引起家兔心律失常的持续时间.ZnS0_4ip20μg/10g可降低CHCl_3引起小鼠室颤率。但ZnSO_4不能降低CaCl_2引起大鼠室颤率,减少哇巴因引起室性早搏和心室颤动的阈剂量和致死量。     

MAGNOLOL REDUCES INFARCT SIZE AND SUPPRESSES VENTRICULAR ARRHYTHMIA IN RATS SUBJECTED TO CORONARY LIGATION

1. Magnolol is an active component of Magnolia officinalis. It is 1000-times more potent than α-tocopherol in inhibiting lipid peroxidation in rat heart mitochondira. In the present study, the in vivo antiarrhythmic and anti-ischaemic effects of magnolol in coronary ligated rats were investigated. 2. Male Sprague-Dawley rats were anaesthetized with urethane. Magnolol, at dosages of 10^?7, 10^?8 and 10^?9 g/kg, was adminstered intravenously 15 min before ligation of the coronary artery. 3. The incidence and duration of ventricular tachycardia and ventricular fibrillation during 30 min coronary ligation were significantly reduced by magnolol. Ventricular arrhythmias during 10 min reperfusion after the relief of coronary ligation were also reduced. 4. In rats subjected to 4h coronary ligation, 10^?7 and 10^?8 g/kg magnolol significantly reduced infarct size. 5. We conclude that magnolol may protect the myocardium against ischaemic injury and suppress ventricular arrhythmia during ischaemia and reperfusion.     

山莨菪碱的抗心律失常作用

山莨菪碱(anisodamine,简称Ani)有阻断M受体和α受体等作用。近年来,有人报道Ani有钙拮抗作用,这可能与茛菪碱类药物用于治疗心律失常有关。本文采用七种实验动物模型,观察了Ani的抗心律失常作用。     

The effects of prostaglandins E2, F2 alpha, prostacyclin, flurbiprofen and aspirin on arrhythmias resulting from coronary artery ligation in anaesthetized rats.

1 Various prostaglandins and inhibitors of prostaglandin synthesis were administered prior to acute coronary artery ligation in anaesthetized rats and their effects were assessed on the number and severity of the resulting early arrhythmias (ventricular ectopic activity; incidence and duration of ventricular tachycardia and of ventricular fibrillation). 2 Prostaglandin E2 (PGE2), PGF2 alpha and prostacyclin all showed antiarrhythmic activity; in contrast flurbiprofen increased the incidence of ventricular fibrillation and mortality. 3 Both the number of ventricular ectopic beats and the incidence of ventricular fibrillation were reduced by aspirin. 4 The results suggest that the release of endogenous PGE2, PGF2 alpha and prostacyclin could reduce early post-infarction ventricular arrhythmias whilst the protective effect of aspirin in this model adds further support for the hypothesis that thromboxane release is involved in the genesis of these arrhythmias.