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Review
. 2023 Aug 24;24(17):13143.
doi: 10.3390/ijms241713143.

Identification of New Antiseizure Medication Candidates in Preclinical Animal Studies

Chih-Sheng Yang  1   2 , Man-Chun Wu  3 , Ming-Chi Lai  4 , Sheng-Nan Wu  5   6 , Chin-Wei Huang  7
Affiliations
Review

Identification of New Antiseizure Medication Candidates in Preclinical Animal Studies

Chih-Sheng Yang et al. Int J Mol Sci. .

Abstract

Epilepsy is a multifactorial neurologic disease that often leads to many devastating disabilities and an enormous burden on the healthcare system. Until now, drug-resistant epilepsy has presented a major challenge for approximately 30% of the epileptic population. The present article summarizes the validated rodent models of seizures employed in pharmacological researches and comprehensively reviews updated advances of novel antiseizure candidates in the preclinical phase. Newly discovered compounds that demonstrate antiseizure efficacy in preclinical trials will be discussed in the review. It is inspiring that several candidates exert promising antiseizure activities in drug-resistant seizure models. The representative compounds consist of derivatives of hybrid compounds that integrate multiple approved antiseizure medications, novel positive allosteric modulators targeting subtype-selective γ-Aminobutyric acid type A receptors, and a derivative of cinnamamide. Although the precise molecular mechanism, pharmacokinetic properties, and safety are not yet fully clear in every novel antiseizure candidate, the adapted approaches to design novel antiseizure medications provide new insights to overcome drug-resistant epilepsy.

Keywords: animal models of seizures; drug-resistant epilepsy; kindling model; maximal electroshock seizure model; novel antiseizure candidates.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Flow diagram of database search.
Figure 2
Figure 2
Schematic flowsheet of novel ASM identification and development, proposed by The Epilepsy Therapy Screening Program, formerly known as ASM Screening Program. Adapted from [19]. 2011, Löscher and Wilcox. Abbreviations: ED50 = median effective dose, LEV = Levetiracetam, LTG = Lamotrigine, MES = maximal electroshock seizure, PTZ = pentylenetetrazole, TD50 = median toxic dose.
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