Linalool and trans-nerolidol prevent pentylenetetrazole-induced seizures in adult zebrafish

Silva, A. L.; Bastos, L. M.; Gallas-Lopes, M.; Chitolina, R.; Reis, C. G.; Nunes, D. S.; Elisabetsky, E.; Herrmann, A. P.; Calcagnotto, M. E.; Piato, A.

doi:10.1101/2025.01.14.633001

bioRxiv · 10.1101/2025.01.14.633001

Linalool and trans-nerolidol prevent pentylenetetrazole-induced seizures in adult zebrafish

Silva, A. L.·Bastos, L. M.·Gallas-Lopes, M.·Chitolina, R.·Reis, C. G.·Nunes, D. S.·Elisabetsky, E.·Herrmann, A. P.·Calcagnotto, M. E.·Piato, A.

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Abstract

BackgroundLinalool (LIN) and trans-nerolidol (NER) are terpene alcohols found in plant-derived essential oils commonly used in traditional systems of medicine. Both compounds have shown antiseizure, sedative, and antioxidant effects in rodent and in vitro models. Due to their structural similarity, a comparative evaluation of their antiseizure profiles is warranted. This study examined the effects of acute LIN and NER exposure in a pentylenetetrazole (PTZ)-induced seizure model in zebrafish (Danio rerio). MethodsA total of 240 adult zebrafish were randomly assigned to the following groups: blank control (dechlorinated water), vehicle control (1% DMSO), positive control (50 {micro}M diazepam, DZP), and three concentrations of LIN or NER (4, 40, 400 {micro}M). Fish were exposed to treatments for 10 minutes, transferred to a washout beaker with dechlorinated water for 5 minutes, and then transferred to PTZ (10 mM) for 20-minute behavioral recording. Seizure activity was scored by blinded observers (BORIS(R)), and locomotion was analyzed with ANY-maze software. ResultsLIN at 400 {micro}M and NER at 40 and 400 {micro}M significantly prolonged latency to clonic- and tonic-like seizures and reduced seizure severity. Notably, 400 {micro}M NER exceeded DZP in effect size, and 40 {micro}M NER also enhanced locomotor activity. ConclusionLIN and NER delayed progression to severe seizure stages and reduced seizure severity, supporting their antiseizure potential. NER consistently outperformed LIN, demonstrating stronger efficacy than DZP at the highest concentration. Consistent with rodent studies, these findings position both as promising leads for drug development.

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Silva, A. L., Bastos, L. M., Gallas-Lopes, M., Chitolina, R., Reis, C. G., Nunes, D. S., Elisabetsky, E., Herrmann, A. P., Calcagnotto, M. E., Piato, A.. 2025-01-16. Linalool and trans-nerolidol prevent pentylenetetrazole-induced seizures in adult zebrafish. https://doi.org/10.1101/2025.01.14.633001

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