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Drug Res (Stuttg) 2024; 74(09): 456-463
DOI: 10.1055/a-2406-5340
Original Article

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

Samane Jahanabadi 
1   Department of Pharmacology and Toxicology, Faculty of Pharmacy, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
2   Pharmaceutical Science Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
,
Mohammadreza Riahi Madvar
1   Department of Pharmacology and Toxicology, Faculty of Pharmacy, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
2   Pharmaceutical Science Research Center, Shahid Sadoughi University of Medical Sciences, Yazd, Iran
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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.

Keywords

5-HT3 antagonist - NMDA receptor - seizure - mice - TNF-α


Publication History

Received: 25 May 2024

Accepted: 20 August 2024

Article published online:
19 September 2024

© 2024. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

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