抗精神病药物和柑橘类黄酮柚皮苷对爪蟾卵母细胞中表达的 HERG 通道的相加抑制作用。

IF 2.9 4区 医学 Q2 PHARMACOLOGY & PHARMACY
Pharmacology Pub Date : 2024-09-26 DOI:10.1159/000541005
Keun-Hang Susan Yang, Dmytro Isaev, Murat Oz
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引用次数: 0

摘要

背景:柑橘汁已被证实会导致健康志愿者的心电图出现 QT 间期延长,而柑橘汁中的主要黄酮类化合物柚皮苷已被确认为导致 QT 间期延长的强效 HERG 通道抑制剂。有报告称,氟哌啶醇、氯丙嗪和氯氮平等几种抗精神病药物也会抑制 HERG 通道,并延长用药患者的 QT 间期。然而,柚皮苷与抗精神病药物对 HERG 通道功能的相互作用尚未得到研究:在本研究中,我们评估了柚皮苷与抗精神病药物联合使用对在爪蟾卵母细胞中表达的 HERG 通道功能的影响:结果:在抗精神病药物(1 µM氟哌啶醇、10 µM氯丙嗪或10 µM氯氮平)中加入30 µM柚皮苷,与单独使用抗精神病药物相比,HERG抑制作用明显增强:结论:研究结果表明,柚皮素与抗精神病药物之间存在相加作用。结论:研究结果表明,柚皮苷与抗精神病药物之间会产生相加作用,这种相加的 HERG 抑制作用会降低再极化储备并可能导致再极化异质性,从而增加心律失常的风险。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Additive Inhibition of HERG Channels Expressed in Xenopus Oocytes by Antipsychotic Drugs and Citrus Juice Flavonoid Naringenin.

Introduction: Citrus juice has been shown to cause QT prolongation in electrocardiograms of healthy volunteers, and naringenin, a major flavonoid found in citrus juice, has been identified as the potent inhibitor of human ether-a-go-go-related gene (HERG) channels as the cause of QT prolongation. Inhibition of HERG channels and prolongation of QT interval by antipsychotic drugs such as haloperidol, chlorpromazine, and clozapine have also been shown. However, naringenin's effect on HERG channel function in conjunction with antipsychotic medications has not been investigated.

Methods: In the present study, we evaluated the effect of combining naringenin with antipsychotics on the function of HERG channels expressed in Xenopus oocytes.

Results: When 30 µm naringenin was added to antipsychotic drugs (1 µm haloperidol, 10 µm chlorpromazine, or 10 µm clozapine), significantly greater HERG inhibition was demonstrated, compared to the inhibition caused by antipsychotic drugs alone. Co-application studies also showed that the magnitudes of inhibitions caused by naringenin + antipsychotics were similar to that predicted by the allotopic interaction model, suggesting that naringenin and antipsychotics bind to the HERG channel at different sites.

Conclusion: The results suggest that there is an additive interaction between antipsychotics and naringenin. Due to the potential for repolarization heterogeneity and a decrease in repolarization reserve, this additive HERG inhibition may increase the risk of arrhythmias.

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来源期刊
Pharmacology
Pharmacology 医学-药学
CiteScore
5.60
自引率
0.00%
发文量
52
审稿时长
6-12 weeks
期刊介绍: ''Pharmacology'' is an international forum to present and discuss current perspectives in drug research. The journal communicates research in basic and clinical pharmacology and related fields. It covers biochemical pharmacology, molecular pharmacology, immunopharmacology, drug metabolism, pharmacogenetics, analytical toxicology, neuropsychopharmacology, pharmacokinetics and clinical pharmacology. In addition to original papers and short communications of investigative findings and pharmacological profiles the journal contains reviews, comments and perspective notes; research communications of novel therapeutic agents are encouraged.
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