Searching for new molecules with antiepileptic potential

ESTEBAN-LÓPEZ, V; SCIOLI MONTOTO, S; RUIZ ME; GAVERNET L; LLANOS M; TALEVI ALAN; LÓPEZ, D.E; SÁNCHEZ-BENITO, D

Simposio; International Partnership Symposium FAPESP/USAL; 2022

Among the different animal models of epilepsy, the GASH/Sal (Genetic Audiogenic Seizure Hamster/Salamanca) resulted in a valuable tool to study new anti-seizure drugs that may lead to the discovery of antiepileptic treatment strategies. These animals exhibit susceptibility to sound-induced seizures. Objectives. The aim of this study is to determine the anti-seizure potential of two TRPV1 channel modulators: novobiocin (NVB) and montelukast (MTK). Both are already used in the treatment of other pathologies. Material and Methods. A total of 12 GASH/Sal hamsters were used in this study. All animals exhibit tonic-clonic seizures before starting the experiment. We evaluate the effect in seizure severity of acute intraperitoneal administrations of 30 mg/kg and 100 mg/kg for both drugs at 30 minutes and 4 hours after treatment. We analyze drug concentration in the blood several times using HPLC. Aproved by the All procedures and experimental protocols were performed in accordance with the guidelines of the European Communities Council Directive (2010/63/UE) for the care and use of laboratory animals and approved by the the Bioethics Committee of the University of Salamanca (application number 380). Results. NVB and MTK produce a decrease in the severity of GASH/Sal seizures, being more effective NVB than MTK. The dosage of 30 mg/kg is enough to produce the anticonvulsant effect, but MTK seems to be more effective than NVB. By HPLC, it is possible to detect levels of both drugs in serum up to 24 hours after administration, reaching the maximum level at 24 minutes, being proportional to the dose used. Conclusions: Both drugs, NVB and MTK, could have a new application as antiepileptic drugs but more studies are necessary to understand their mechanism of action and the right dosage.