ArticleNeurochemical research2026
Cenobamate and Trazodone Combination Suppresses Seizures, EEG Alterations, Preserves Neuronal Architecture and Normalizes the BDNF/TrkB Expression in PTZ‑Kindled Mice.
Article in Neurochemical research, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Polytherapy is increasingly needed to overcome the limitations of monotherapy in epilepsy and its comorbidities. Therefore, we investigated the effect of cenobamate (CNB, 30 mg/kg) and trazodone (TZ, 10 mg/kg), alone and in combination, in PTZ-kindling model, where mice received 11 doses of pentylenetetrazole (PTZ, 40 mg/kg) every other day for three weeks. Behavioral seizure scoring, electroencephalographic (EEG) changes at the 1st, 5th, and 11th injections, molecular markers, and hippocampal histopathology were assessed. TZ + CNB suppressed seizure progression with no tonic-clonic seizures observed throughout kindling period (p < 0.0001), whereas monotherapy by these drugs showed no significant suppression. PTZ produced the most pronounced EEG abnormalities, which CNB and TZ alone did not differ significantly. Combination therapy revealed the greatest reductions across all EEG parameters (q = 0.0004-0.0014), approaching near-baseline values by the 11th injection. Furthermore, brain homogenates were assessed for BDNF, GFAP, and TrkB expression levels by RT-PCR. CNB showed mixed effects (p = 0.0081-0.0631), while TZ (p = 0.0971-0.1422) produced no significant difference from PTZ40. TZ + CNB shifted these markers toward normal levels (p = 0.0001-0.0054), outperforming monotherapies. Hippocampal Nissl-stained sections showed neurodegenerative damage with monotherapies across all regions, while TZ + CNB exhibited substantial preservation, with minimal alteration in hippocampal and cortical architecture. These parallel findings suggest that positive allosteric GABA
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