<abstract xmlns="http://www.w3.org/1999/xhtml"><bold>Objective</bold>: This study evaluated the anticonvulsant action of lacosamide (LCS), a novel drug that was recently approved for the treatment of partial or secondarily generalized seizures, using an animal model of generalized epilepsy induced by repetitive pentylenetetrazole (PTZ) administration in rats. The main goal was to evaluate the behavioral pattern of lacosamide action by classifying seizures according to a modi Racine-scale. Furthermore, the reproducibility of the win-PTZ kindling model of epilepsy, a recently described variant of the standard PTZ-kindling model, was also assessed.<bold>Methods</bold>: Adult male Wistar rats (n=16) were divided into two groups and underwent the win-PTZ-kindling protocol in two independent trials. After finishing the kindling procedure, all animals, which presented stage 5 seizures were tested for the anticonvulsant action of lacosamide at three different doses (3, 10, and 30 mg/kg).<bold>Results</bold>: The maximal severity of seizures decreased and the latency to stage 3-5 seizures increased when the animals were treated with lacosamide at a single dose of 10 mg/kg compared to saline pretreatment (p &lt; 0.05), both parameter reflecting an anticonvulsant action of the drug. Unfortunately, the number of stage 3-5 seizures also increased, but not significantly. The win-PTZ kindling model showed an adequate reproducibility between different trials, however, the number of fully kindled rats was lower than previously reported.<bold>Conclusions</bold>: Lacosamide showed a convincing anticonvulsant action in the win-PTZ kindling model of epilepsy by preventing the generalization of seizures. The win-PTZ kindling model was proved to be useful for studying epileptogenesis and the anticonvulsant action of drugs.</abstract>

Objective: This study evaluated the anticonvulsant action of lacosamide (LCS), a novel drug that was recently approved for the treatment of partial or secondarily generalized seizures, using an animal model of generalized epilepsy induced by repetitive pentylenetetrazole (PTZ) administration in rats. The main goal was to evaluate the behavioral pattern of lacosamide action by classifying seizures according to a modi Racine-scale. Furthermore, the reproducibility of the win-PTZ kindling model of epilepsy, a recently described variant of the standard PTZ-kindling model, was also assessed.Methods: Adult male Wistar rats (n=16) were divided into two groups and underwent the win-PTZ-kindling protocol in two independent trials. After finishing the kindling procedure, all animals, which presented stage 5 seizures were tested for the anticonvulsant action of lacosamide at three different doses (3, 10, and 30 mg/kg).Results: The maximal severity of seizures decreased and the latency to stage 3-5 seizures increased when the animals were treated with lacosamide at a single dose of 10 mg/kg compared to saline pretreatment (p < 0.05), both parameter reflecting an anticonvulsant action of the drug. Unfortunately, the number of stage 3-5 seizures also increased, but not significantly. The win-PTZ kindling model showed an adequate reproducibility between different trials, however, the number of fully kindled rats was lower than previously reported.Conclusions: Lacosamide showed a convincing anticonvulsant action in the win-PTZ kindling model of epilepsy by preventing the generalization of seizures. The win-PTZ kindling model was proved to be useful for studying epileptogenesis and the anticonvulsant action of drugs.

Lacosamide Reduces Seizure Severity but Increases Seizure Frequency in PTZ-Kindled Rats

Faculty of Pharmacy, Department of Pharmacology and Clinical Pharmacy

University of Medicine and Pharmacy of Tirgu Mures

Acta Marisiensis - Seria Medica

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

Objective: This study evaluated the anticonvulsant action of lacosamide (LCS), a novel drug that was recently approved for the treatment of partial or...

Lacosamide Reduces Seizure Severity but Increases Seizure Frequency in PTZ-Kindled Rats

Published Online: Dec 30, 2017

Page range: 173 - 177

Received: Oct 10, 2017

Accepted: Nov 13, 2017

DOI: https://doi.org/10.1515/amma-2017-0037

Keywords
lacosamide, anticonvulsant, kindling, epilepsy

© 2017 Zsolt Gáll et al., published by De Gruyter Open

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

Lacosamide Reduces Seizure Severity but Increases Seizure Frequency in PTZ-Kindled Rats

Published Online: Dec 30, 2017

Page range: 173 - 177

Received: Oct 10, 2017

Accepted: Nov 13, 2017

DOI: https://doi.org/10.1515/amma-2017-0037

Keywordslacosamide, anticonvulsant, kindling, epilepsy

© 2017 Zsolt Gáll et al., published by De Gruyter Open

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

Keywords
lacosamide, anticonvulsant, kindling, epilepsy