Naltrexone, an Opioid Antagonist, Decreases Seizure Activity In Vitro and In Vivo
Abstract number :
2.19
Submission category :
7. Anti-seizure Medications / 7A. Animal Studies
Year :
2021
Submission ID :
1826130
Source :
www.aesnet.org
Presentation date :
12/5/2021 12:00:00 PM
Published date :
Nov 22, 2021, 06:52 AM
Authors :
Rachel Langton, BS - University of Iowa; Morgan Sturgeon, PhD - Research Scientist III, Integrated DNA Technologies; Shaunik Sharma, PhD - Postdoctoral Research Scholar, Pediatrics, University of Iowa; Robert Cornell, PhD - Professor, Anatomy & Cell Biology, University of Iowa; Alexander Bassuk, MD, PhD - Professor, Pediatrics, University of Iowa; Joseph Glykys, MD, PhD - Assistant Professor, Pediatrics, University of Iowa
Rationale: Many epileptic patients fail to respond to available anticonvulsive medications, and novel drugs are needed. Drug repositioning is a strategy to decrease the time and costs for medicines to reach patients by using previously approved drugs for new indications. Therefore, we evaluated FDA-approved drugs to find medications that have anticonvulsive properties.
Methods: We evaluated candidate anticonvulsant drugs, determined by our prior transcriptomics analysis of hippocampal tissue, in a larval zebrafish model of human Dravet Syndrome (scn1Lab mutants), in wild-type zebrafish larvae treated with the pro-convulsant drug pentylenetetrazole (PTZ), in wild-type C57bl/6J acute brain slices exposed to PTZ, and in wild-type mice treated with PTZ in vivo. Abnormal locomotion was determined behaviorally in zebrafish and mice and through field potentials in neocortex layer IV/V and hippocampal CA1 stratum pyramidale.
Results: The opioid antagonist naltrexone (75 μM) decreased abnormal locomotion in the larval zebrafish model of human Dravet Syndrome (scn1Lab mutants) and wild-type larvae treated with the pro-convulsant drug PTZ. Naltrexone (75 μM) decreased seizure-like events in the neocortex of acute brain slices of wild-type mice, but not in the hippocampus CA1 stratum pyramidale. This same dose of naltrexone further reduced seizure-like events in the presence of valproic acid. In vivo, naltrexone reduced the duration and number of convulsive seizures in wild-type adult mice injected with PTZ.
Conclusions: Our results reveal that the opioid antagonist naltrexone has anticonvulsive properties and is a candidate drug for seizure treatment.
Funding: Please list any funding that was received in support of this abstract.: AGB was supported by NIH R01NS098590 and the UNIDM/Tross Family Fund. JG was supported by NIH/NINDS K08NS091248, R01NS115800, and the Iowa Neuroscience Institute.
Anti-seizure Medications