Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review

Animal Models of Pharmacoresistant Epilepsy

Michelle Guignet, H. Steve White
Jeffrey L. Noebels  1 , Massimo Avoli  2 , Michael A. Rogawski  3 , Annamaria Vezzani  4 , Antonio V. Delgado-Escueta  5
, editors.
In: Jasper's Basic Mechanisms of the Epilepsies. 5th edition. New York: Oxford University Press; 2024. Chapter 66.
Affiliations
Free Books & Documents
Review

Animal Models of Pharmacoresistant Epilepsy

Michelle Guignet et al.
Free Books & Documents

Excerpt

Recognizing the pressing need for better treatment options for pharmacoresistant patients with epilepsy, collaborative efforts among the NINDS Epilepsy Therapy Screening Program, the pharmaceutical industry, and academia have focused on the inclusion of therapy-resistant animal models for the screening and characterization of novel compounds that offer more effective seizure control for a difficult-to-treat population. This chapter discusses the role of the 6 Hz psychomotor seizure model, the lamotrigine- and phenytoin-resistant kindled rodent models of focal epilepsy, and the post–status epilepticus models of spontaneous recurring seizures in the antiseizure drug discovery process. While each of these models reproduces some aspects of the pathological, behavioral, and pharmacological characteristics of pharmacoresistant seizures in humans, their clinical validity has yet to be established. However, the approval of cenobamate (CBM) in 2019, an ASD with remarkable clinical efficacy (~20% seizure freedom) and profound preclinical efficacy in the 6 Hz test, opens the door to reevaluate these animal seizure models with renewed hope and optimism. While it would have been premature to speculate on the predictive clinical efficacy of CBM based on only the 6 Hz test, it does provide hope that existing animal models can identify new drugs and potentially change the landscape for pharmacoresistance in the future.

PubMed Disclaimer

Similar articles

See all similar articles

References

    1. Ali, A., et al. (2012). “A once-per-day, drug-in-food protocol for prolonged administration of antiepileptic drugs in animal models.” Epilepsia 53(1): 199–206. - PubMed
    1. Bankstahl, M., et al. (2012). “Inter-individual variation in the anticonvulsant effect of phenobarbital in the pilocarpine rat model of temporal lobe epilepsy.” Exp Neurol 234(1): 70–84. - PubMed
    1. Barton, M. E., et al. (2001). “Pharmacological characterization of the 6 Hz psychomotor seizure model of partial epilepsy.” Epilepsy Res 47(3): 217–227. - PubMed
    1. Ben-Ari, Y., et al. (1979). “A new model of focal status epilepticus: intra-amygdaloid application of kainic acid elicits repetitive secondarily generalized convulsive seizures.” Brain Res 163(1): 176–179. - PubMed
    1. Bethmann, K., et al. (2007). “Resistance to phenobarbital extends to phenytoin in a rat model of temporal lobe epilepsy.” Epilepsia 48(4): 816–826. - PubMed

LinkOut - more resources