Unraveling the Interplay of 5-hydroxytryptamine-3 and N-methyl-d-aspartate Receptors in Seizure Susceptibility.

IF 1.7 Q3 PHARMACOLOGY & PHARMACY
Drug Research Pub Date : 2024-11-01 Epub Date: 2024-09-19 DOI:10.1055/a-2406-5340
Samane Jahanabadi, Mohammadreza Riahi Madvar
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引用次数: 0

Abstract

Background: Epilepsy, a prevalent neurological disorder characterized by recurrent seizures, presents significant challenges in treatment and management. This study aimed to evaluate the effect of tropisetron, a selective 5-HT3 receptor antagonist on pentylenetetrazole (PTZ) - induced seizure in mice by exploring the potential role of the NMDA receptor and inflammatory responses.

Methods: For this purpose, seizures were induced by intravenous PTZ infusion. Tropisetron at 1-, 2-, 3-, 5-, 10- mg/kg were administered intraperitoneally 30 minutes before PTZ. To evaluate probable role of NMDA signaling, selective NMDAR antagonists, ketamine and MK-801, were injected 15 minutes before tropisetron. Also, TNF-α level of hippocampus were measured following administration of mentioned drugs in mice.

Results: Our results demonstrate that tropisetron displayed a dose-dependent impact on seizure threshold, with certain doses (5 and 10 mg/kg) exhibiting anticonvulsant properties. In addition, the noncompetitive NMDAR antagonists, ketamine (1 mg/kg) and MK-801 (0.5 mg/kg), at doses that had no effect on seizure threshold, augmented the anticonvulsant effect of tropisetron (3 mg/kg). Also, tropisetron led to a reduction in hippocampal TNF-α levels, indicating its anti-inflammatory potential independent of 5-HT receptor activity.

Conclusion: In conclusion, we demonstrated that the anticonvulsant effect of tropisetron is mediated by the inhibition of NMDA receptors and a decline in hippocampal TNF-α level. These findings highlight a potential connection between 5-HT3 and NMDA receptors in the pharmacological treatment of inflammatory diseases, such as seizure, warranting further investigation into their combined therapeutic effects.

揭示5-羟色胺-3和N-甲基-d-天冬氨酸受体在癫痫易感性中的相互作用
背景:癫痫是一种以反复发作为特征的流行性神经系统疾病,给治疗和管理带来了巨大挑战。本研究旨在通过探讨 NMDA 受体和炎症反应的潜在作用,评估选择性 5-HT3 受体拮抗剂托品司琼对戊四氮唑(PTZ)诱导的小鼠癫痫发作的影响:方法:为此,通过静脉注射 PTZ 诱导癫痫发作。在注射 PTZ 前 30 分钟腹腔注射 1、2、3、5、10 毫克/千克的托吡司琼。为评估NMDA信号传导的可能作用,在托吡司琼注射前15分钟注射选择性NMDAR拮抗剂氯胺酮和MK-801。此外,在给小鼠注射上述药物后,还测量了海马的 TNF-α 水平:结果:我们的研究结果表明,托品司琼对癫痫发作阈值的影响呈剂量依赖性,某些剂量(5 和 10 毫克/千克)具有抗惊厥特性。此外,非竞争性 NMDAR 拮抗剂氯胺酮(1 毫克/千克)和 MK-801(0.5 毫克/千克)的剂量对癫痫发作阈值没有影响,但却增强了托吡司琼(3 毫克/千克)的抗惊厥作用。此外,托品司琼还能降低海马TNF-α的水平,这表明托品司琼具有独立于5-羟色胺受体活性的抗炎潜力:总之,我们证明了托吡司琼的抗惊厥作用是通过抑制 NMDA 受体和降低海马 TNF-α 水平来实现的。这些发现凸显了 5-HT3 和 NMDA 受体在癫痫发作等炎症性疾病的药物治疗中的潜在联系,值得进一步研究它们的联合治疗效果。
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来源期刊
Drug Research
Drug Research PHARMACOLOGY & PHARMACY-
CiteScore
3.50
自引率
0.00%
发文量
67
期刊介绍: Drug Research (formerly Arzneimittelforschung) is an international peer-reviewed journal with expedited processing times presenting the very latest research results related to novel and established drug molecules and the evaluation of new drug development. A key focus of the publication is translational medicine and the application of biological discoveries in the development of drugs for use in the clinical environment. Articles and experimental data from across the field of drug research address not only the issue of drug discovery, but also the mathematical and statistical methods for evaluating results from industrial investigations and clinical trials. Publishing twelve times a year, Drug Research includes original research articles as well as reviews, commentaries and short communications in the following areas: analytics applied to clinical trials chemistry and biochemistry clinical and experimental pharmacology drug interactions efficacy testing pharmacodynamics pharmacokinetics teratology toxicology.
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