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The opioid antagonist naltrexone decreases seizure-like activity in genetic and chemically induced epilepsy models

Morgan L Sturgeon1, Rachel Langton2,3, Shaunik Sharma4

  • 1Department of Anatomy and Cell Biology, University of Iowa, Iowa City, IA, USA.

Epilepsia Open
|October 19, 2021
PubMed
Abstract

Insights

Naltrexone, an opioid antagonist, demonstrates anticonvulsant properties. This study validates naltrexone as a promising candidate for developing new seizure treatments for epilepsy patients.

Area of Science:

  • Neuroscience
  • Pharmacology
  • Epilepsy Research

Background:

  • Many epilepsy patients are unresponsive to current anticonvulsant medications.
  • There is a critical need for novel anticonvulsant therapies.

Purpose of the Study:

  • To identify new anticonvulsant drugs by screening FDA-approved medications not previously known for anticonvulsant activity.
  • To evaluate the efficacy of naltrexone as a potential treatment for seizures.

Main Methods:

  • Screening was performed using a larval zebrafish model of Dravet syndrome and pentylenetetrazole (PTZ)-induced seizures.
  • Further validation was conducted in mouse acute brain slices and in vivo PTZ-induced seizure models.
  • Abnormal locomotion and seizure activity were assessed behaviorally and electrophysiologically.

Main Results:

  • Naltrexone significantly reduced abnormal locomotion in zebrafish models of epilepsy.
  • Naltrexone decreased seizure-like events in mouse brain slices.
  • Naltrexone diminished the duration and frequency of seizures in adult mice.

Conclusions:

  • Naltrexone exhibits significant anticonvulsant properties across multiple epilepsy models.
  • Naltrexone is a promising candidate drug for the development of novel seizure treatments.
Keywords:
scn1LabZebrafishdrug repurposemicenaltrexonepentylenetetrazole

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