Preventive and therapeutic effects of magnesium sulfate on nikethamide-induced seizures: Implications for COVID-19 treatment

doi:10.5662/wjm.v15.i4.105775

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World Journal of Methodology

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World J Methodol. Dec 20, 2025; 15(4): 105775
Published online Dec 20, 2025. doi: 10.5662/wjm.v15.i4.105775

Preventive and therapeutic effects of magnesium sulfate on nikethamide-induced seizures: Implications for COVID-19 treatment

Dao-Jian Xu, Qiang Zhong, Guo-Tao Wang, Xiang Lu

Dao-Jian Xu, Qiang Zhong, Guo-Tao Wang, Xiang Lu, Department of Emergency, Taizhou Municipal Hospital, Taizhou 318099, Zhejiang Province, China

Author contributions: Xu DJ was responsible for data curation and writing of the original draft; Zhong Q was responsible for methodology and software; Wang GT was responsible for formal analysis and resources; Lu X was responsible for conceptualization, writing, reviewing and editing; all the authors participated in drafting the manuscript, and all the authors read, contributed to, and approved the final version of the manuscript.

Supported by The Zhejiang Provincial Health Commission, No. 2022KY1391.

Institutional review board statement: This study was conducted in accordance with the ethical guidelines for animal research and was approved by the Ethics Committee of Taizhou University.

Institutional animal care and use committee statement: All animal experiments were reviewed and approved by the Institutional Animal Care and Use Committee of Taizhou University. The study followed the national and institutional guidelines for the care and use of laboratory animals, ensuring ethical handling and welfare throughout the experimental procedures.

Conflict-of-interest statement: All authors declare no conflict of interest in publishing the manuscript.

ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.

Data sharing statement: The datasets generated and analyzed during the current study are available from the corresponding author upon reasonable request.

Corresponding author: Xiang Lu, PhD, Department of Emergency, Taizhou Municipal Hospital, No. 381 Zhongshan East Road, Jiaojiang District, Taizhou 318099, Zhejiang Province, China. cqlu1978@126.com

Received: February 7, 2025
Revised: March 12, 2025
Accepted: March 20, 2025
Published online: December 20, 2025
Processing time: 179 Days and 6.4 Hours

Abstract

BACKGROUND

Nikethamide, a respiratory stimulant, is used to treat hypoxemia caused by coronavirus disease 2019 (COVID-19), but it carries a risk of convulsions. Magnesium sulfate (MgSO₄), a seizure inhibitor, might serve as a rescue agent against nikethamide-induced seizures.

AIM

To investigate the therapeutic effect of MgSO₄ on nikethamide -induced seizures in COVID-19 patients through animal experiments, providing experimental support for the clinical application of MgSO₄ in preventing and treating seizures caused by nikethamide.

METHODS

Forty mice were randomly divided into four groups: (1) Physiological saline; (2) Low-dose MgSO₄ (50 mg/kg); (3) Medium-dose MgSO₄ (100 mg/kg); and (4) High-dose MgSO₄ (200 mg/kg). After 15 minutes of intraperitoneal injection of different doses of MgSO₄ or an equal volume of physiological saline, the mice were injected with nikethamide (250 mg/kg).

RESULTS

Compared to the normal saline group, all doses of MgSO₄ significantly prolonged the seizure latency and reduced the severity of convulsions. However, they also extended the duration of seizures and correspondingly increased survival time (P < 0.05). The incidence of seizures and mortality rate in the MgSO₄-treated groups were significantly lower than those in the normal saline group (P < 0.05).

CONCLUSION

MgSO₄ can prevent and treat seizures caused by nikethamide in mice. This finding has implications for the application of MgSO₄ in treating and preventing seizures caused by nikethamide in COVID-19 treatment.

Keywords: COVID-19; Drug discovery; Hypoxemia; Magnesium sulfate; Nikethamide; Seizures

Core Tip: Nikethamide is a respiratory stimulant used for the treatment of coronavirus disease 2019 (COVID-19); however, its use carries the risk of seizure induction. This study demonstrates that magnesium sulfate (MgSO₄) can effectively prevent and mitigate nikethamide-induced seizures in a dose-dependent manner. The results indicate that MgSO₄ prolongs seizure latency, reduces seizure severity, extends seizure duration, and decreases mortality in the experimental model. These findings provide important insights into the potential clinical application of MgSO₄ for managing nikethamide-associated seizure complications in COVID-19 patients.