新开发的普罗帕酮衍生物的抗心律失常作用

Q4 Pharmacology, Toxicology and Pharmaceutics Arhiv za Farmaciju Pub Date : 2022-01-01 DOI:10.5937/arhfarm72-37114
B. Ivković, D. Opačić, B. Dzudovic, Milkica Crevar, L. Gojković-Bukarica
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引用次数: 0

摘要

众所周知,药物分子中不同化学基团的存在会影响其药理学性质。我们的研究目的是探讨新合成的普罗帕酮衍生物,其苯基部分的变化是否与普罗帕酮对心律失常的影响不同。5OCl-PF和5OF-PF是在苯基部分的邻位上具有-Cl或-F取代基的普罗帕酮衍生物。为了验证其抗心律失常的作用,我们使用了乌头碱诱发心律失常的体内大鼠模型。5OCl-PF比乌头碱更能加速室上性早搏(SVPB)的出现和死亡。所有接受5OCl-PF治疗的动物均出现齐射性室性早搏(VPBS)、双心室性早搏(VPBB)和阵发性室性心动过速(PVT)。5OF-PF具有负变时作用,增强心房兴奋性(更多的SVPB)。对室上性心动过速、VPBS、ptt的发生及起病时间均有积极影响。根据所得结果,新合成的propaenone衍生物的抗心律失常作用并不优于母体化合物。在未来,我们的研究将集中在不同衍生物的合成和研究其抗心律失常的作用。
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Antiarrhythmic effects of newly developed propafenone derivatives
It is well known that the presence of different chemical groups in drug molecules influences their pharmacological properties. The aim of our study is to investigate whether newly synthesized derivatives of propafenone, with changes in benzyl moiety, have a different effect upon arrhythmia, compared to propafenone. 5OCl-PF and 5OF-PF are derivatives of propafenone with -Cl or -F substituent on the ortho position of the benzyl moiety. For verification of their antiarrhythmic effect, we used an in vivo rat model of aconitine-induced arrhythmia. 5OCl-PF speeded the appearance of supraventricular premature beats (SVPB) and death more than aconitine. All animals treated with 5OCl-PF developed ventricular premature beats in salvos (VPBS), bigeminies (VPBB) and paroxysmal ventricular tachycardia (PVT). 5OF-PF had a negative chronotropic effect and potentiated atrial excitability (more SVPB). It had a positive effect on the occurrence and onset time of supraventricular tachycardia, VPBS, and PVT. Based on the obtained results, it can be concluded that newly synthesized propafenone derivatives have no better antiarrhythmic effect than the parent compound. In the future, our research will be focused on the synthesis of different derivatives and examining their antiarrhythmic effects.
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来源期刊
Arhiv za Farmaciju
Arhiv za Farmaciju Pharmacology, Toxicology and Pharmaceutics-Pharmaceutical Science
自引率
0.00%
发文量
19
审稿时长
12 weeks
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