Since 1993, over 20 new anti-seizure drugs (ASDs) have been identified in well-established animal seizure and epilepsy models and subsequently demonstrated to be clinically effective in double-blinded, placebo-controlled clinical trials in patients with focal onset seizures. All clinically-available ASDs on the market today are effective in at least one of only three preclinical seizure and epilepsy models: the acute maximal electroshock (MES), the acute subcutaneous pentylenetetrazol (scPTZ) test, or the kindled rodent with chronic evoked seizures. Thus, it reasons that preclinical ASD development does not need significant revision to successfully identify ASDs for the symptomatic treatment of epilepsy. Unfortunately, a significant need still persists for more efficacious and better tolerated ASDs. This is particularly true for those patients whose seizures remain drug resistant. This review will focus on the continued utility of the acute MES and scPTZ tests, as well as the kindled rodent for current and future ASD development. These are the only "clinically validated" rodent models to date and been heavily used in the search for novel and more efficacious ASDs. This is to say that promising ASDs have been brought to the clinic on the basis of efficacy in these particular seizure and epilepsy models alone. This review also discusses some of the inherent advantages and limitations of these models relative to existing and emerging preclinical models. It then offers insight into future efforts to develop a preclinical model that will advance a truly transformative therapy for the symptomatic treatment of difficult to treat focal onset epilepsy.
Validated animal models for antiseizure drug (ASD) discovery: Advantages and potential pitfalls in ASD screening.
Melissa Barker-Haliski,H. Steve White
Published 2020 in Neuropharmacology
ABSTRACT
PUBLICATION RECORD
- Publication year
2020
- Venue
Neuropharmacology
- Publication date
2020-05-01
- Fields of study
Medicine
- Identifiers
- External record
- Source metadata
Semantic Scholar, PubMed
CITATION MAP
EXTRACTION MAP
CLAIMS
CONCEPTS
- anti-seizure drugs (asds)
The therapeutic drug class used to prevent or reduce seizures and serve as the focus of the review.
Aliases: ASDs, anti-seizure drugs, antiseizure drugs
- clinically validated rodent models
The rodent seizure models discussed as having translated to clinically effective antiseizure drugs in human trials.
Aliases: clinically validated models
- difficult-to-treat focal onset epilepsy
Focal epilepsy with seizures that remain hard to control with medication, motivating better therapies.
Aliases: drug-resistant focal onset epilepsy, difficult to treat focal onset epilepsy
- kindled rodent model
A chronic evoked-seizure rodent model created by repeated stimulation and used to evaluate antiseizure compounds.
Aliases: kindling model, kindled rat model
- maximal electroshock (mes) test
An acute rodent seizure assay that uses electroshock to induce seizures for antiseizure drug screening.
Aliases: MES test, MES
- preclinical model
An experimental model used before clinical testing to evaluate candidate therapies.
Aliases: animal model, preclinical assay
- subcutaneous pentylenetetrazol (scptz) test
An acute rodent seizure assay that uses subcutaneous pentylenetetrazol to provoke seizures for drug screening.
Aliases: scPTZ test, PTZ test
REFERENCES
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