PUBLICATION
Memantine Confers Multi-Target Protection in a Zebrafish Seizure Model: Attenuating Epileptic Behavior, GluN2A Overexpression, and Oxidative Stress
- Authors
- Zenki, K.C., Kalinine, E., Mussulini, B.H.M., Dos Santos, T.G., von Mengden, L., Klamt, F., Baggio, S., de Moura, A.C., da Veiga, A.B.G., de Oliveira, D.L.
- ID
- ZDB-PUB-260103-5
- Date
- 2026
- Source
- Journal of neurochemistry 170: e70345 (Journal)
- Registered Authors
- Keywords
- anxiety, drug repurposing, memantine, seizure, zebrafish
- MeSH Terms
-
- Animals
- Anticonvulsants/pharmacology
- Disease Models, Animal
- Excitatory Amino Acid Antagonists/pharmacology
- Male
- Memantine*/pharmacology
- Memantine*/therapeutic use
- Neuroprotective Agents*/pharmacology
- Oxidative Stress*/drug effects
- Oxidative Stress*/physiology
- Pentylenetetrazole/toxicity
- Receptors, N-Methyl-D-Aspartate*/antagonists & inhibitors
- Receptors, N-Methyl-D-Aspartate*/biosynthesis
- Receptors, N-Methyl-D-Aspartate*/genetics
- Receptors, N-Methyl-D-Aspartate*/metabolism
- Seizures*/chemically induced
- Seizures*/drug therapy
- Seizures*/metabolism
- Seizures*/prevention & control
- Zebrafish
- PubMed
- 41480919 Full text @ J. Neurochem.
Citation
Zenki, K.C., Kalinine, E., Mussulini, B.H.M., Dos Santos, T.G., von Mengden, L., Klamt, F., Baggio, S., de Moura, A.C., da Veiga, A.B.G., de Oliveira, D.L. (2026) Memantine Confers Multi-Target Protection in a Zebrafish Seizure Model: Attenuating Epileptic Behavior, GluN2A Overexpression, and Oxidative Stress. Journal of neurochemistry. 170:e70345.
Abstract
Drug repurposing represents a strategic approach to identifying multi-target therapies for complex disorders like refractory epilepsy. Memantine (MN), a well-tolerated N-methyl-D-aspartate receptor (NMDAR) antagonist with additional multi-target activities, is a promising candidate for repurposing. This study investigated the preventive effects of MN on pentylenetetrazol (PTZ)-induced seizures and its associated neurochemical and behavioral sequelae in adult zebrafish. Animals were pre-treated with MN (20 or 50 mg/kg, i.p.) or vehicle 1 or 2 h before PTZ exposure. Seizure behavior was assessed immediately, while neurochemical and behavioral analyses were conducted 24 h post-seizure. MN pre-treatment significantly attenuated seizure severity and delayed the onset of tonic-clonic seizures. Notably, MN prevented the PTZ-induced upregulation of the GluN2A NMDAR subunit and mitigated oxidative stress by reducing protein carbonylation and normalizing superoxide dismutase (SOD) activity. Furthermore, MN abolished the PTZ-induced increase in time spent in the white compartment of a light/dark test, a behavioral indicator of disrupted defensive responses. These results demonstrate that MN confers robust anticonvulsant, neuroprotective, and behavioral-stabilizing effects in a zebrafish seizure model. Our findings reinforce the potential of memantine as a novel multi-target adjunct therapy for mitigating the neurobehavioral consequences of epilepsy.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping