Evidence map›Paper›PMID 39212337›Full record

ArticleEpilepsia2024

Utilizing an acute hyperthermia-induced seizure test and pharmacokinetic studies to establish optimal dosing regimens in a mouse model of Dravet syndrome.

Jeffrey A Mensah, Kristina Johnson, Tia Freeman, Christopher A Reilly, Joseph E Rower, Cameron S Metcalf, Karen S Wilcox

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Epilepsia, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors.

Jeffrey A MensahDepartment of Pharmacology and Toxicology, University of Utah, Salt Lake City, Utah, USA.ORCID https://orcid.org/0000-0001-7026-9329
Kristina JohnsonContract Site of the National Institute of Neurological Disorders and Stroke Epilepsy Therapy Screening Program, Salt Lake City, Utah, USA.
Tia FreemanCenter for Human Toxicology, Salt Lake City, Utah, USA.
Christopher A ReillyDepartment of Pharmacology and Toxicology, University of Utah, Salt Lake City, Utah, USA.ORCID https://orcid.org/0000-0002-5006-1982
Joseph E RowerDepartment of Pharmacology and Toxicology, University of Utah, Salt Lake City, Utah, USA.ORCID https://orcid.org/0000-0003-3629-7902
Cameron S MetcalfDepartment of Pharmacology and Toxicology, University of Utah, Salt Lake City, Utah, USA.ORCID https://orcid.org/0000-0002-1510-0405
Karen S WilcoxDepartment of Pharmacology and Toxicology, University of Utah, Salt Lake City, Utah, USA.ORCID https://orcid.org/0000-0003-2660-8826

Funding

SCREENING OF INVESTIGATIONAL THERAPEUTICS TO TREAT, MODIFY OR PREVENT EPILEPSY FOR THE NINDS EPILEPSY THERAPY SCREENING PROGRAM (ETSP)75N95022C00007 · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · 2025 to 2025
$5.4M
Donald R. Gehlert Fellowship, University of Utah College of PharmacyNational Institute of Neurological Disorders and Stroke, Epilepsy Therapy Screening Program, National Institutes of Health, and Department of Health and Human Services HHS 75N95022C00007NIDA NIH HHS 75N95022C00007NIDA NIH HHS HHSN271201600048C
6 · The paper itself

Abstract

objectiveThe current standard of care for Dravet syndrome (DS) includes polytherapy after inadequate seizure control with one or more monotherapy approaches. Treatment guidelines are often based on expert opinions, and finding an optimal balance between seizure control and adverse drug effects can be challenging. This study utilizes the efficacy and pharmacokinetic assessment of a second-line treatment regimen that combines clobazam and sodium valproate with an add-on drug as a proof-of-principle approach to establish an effective therapeutic regimen in a DS mouse model.

methodsWe evaluated the efficacy of add-on therapies stiripentol, cannabidiol, lorcaserin, or fenfluramine added to clobazam and sodium valproate against hyperthermia-induced seizures in Scn1a

resultsHigher doses of stiripentol or cannabidiol, in combination with clobazam and sodium valproate, were effective against hyperthermia-induced seizures in Scn1a SIGNIFICANCE: A polypharmacy strategy may be a practical preclinical approach to identifying efficacious compounds for DS. The drug-drug interactions between compounds used in this study may explain the potentiated efficacy of some polytherapies.

Indexed as

AnticonvulsantsCannabidiolClobazamDioxolanesDisease Models, AnimalEpilepsies, MyoclonicHyperthermiaValproic AcidAnimalsDose-Response Relationship, DrugDrug Therapy, CombinationFenfluramineMaleMiceMice, TransgenicNAV1.1 Voltage-Gated Sodium ChannelAnticonvulsantsCannabidiolClobazamDioxolanesFenfluramineNAV1.1 Voltage-Gated Sodium ChannelScn1a protein, mousestiripentolValproic Acidantiseizure drugsDravet syndromehyperthermia‐induced seizure modelpharmacokineticstriple‐drug therapy

Identifiers

PMID39212337
PMCPMC11496002

What Socratic holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.