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

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 modified 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-PTZkindling 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.

The problem of “structural integration”. A case study of the 9th‒10th century burials (Graves 49 and 50) at Hortobágy – Árkus

“…Nonetheless, when looking at the broader geographical area around the microregion of the Hortobágy and its Conquest Period archaeology, the picture becomes more differentiated. To the southeast, one finds a fine example of the so called "sabretache plate -circle" 41 , namely, the sabretache plate of Báránd 42 . In the surroundings of Báránd, beyond the eastern perimeter of the Hortobágy, there is the completely excavated burial site at Püspökladány -Hízóföld, the starting date of which could be set around 960/970 43 .…”