Evidence map›Paper›PMID 39028384›Full record

ArticlePharmacological reports : PR2024

Padsevonil suppresses seizures without inducing cell death in neonatal rats.

Sean Quinlan, Eric Witherspoon, Patrick A Forcelli

Abstract read
In one paragraph

Article in Pharmacological reports : PR, 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. Review
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

3 authors.

Sean Quinlan *Department of Pharmacology & Physiology, Georgetown University, New Research Bldg., W209B, 3970 Reservoir Road NW, Washington, DC, 20007, USA.
Eric Witherspoon *Department of Pharmacology & Physiology, Georgetown University, New Research Bldg., W209B, 3970 Reservoir Road NW, Washington, DC, 20007, USA.
Patrick A ForcelliDepartment of Pharmacology & Physiology, Georgetown University, New Research Bldg., W209B, 3970 Reservoir Road NW, Washington, DC, 20007, USA. paf22@georgetown.edu.ORCID http://orcid.org/0000-0003-1763-060X

Funding

Structural and functional sequelae of neonatal anticonvulsant exposure: drug-seizure interactionsR01HD091994 · NICHD · GEORGETOWN UNIVERSITY · PI FORCELLI, PATRICK ALEXANDER · 2018 to 2022
$2.9M
Pharmacological Sciences Training Program (PSTP)T32GM142520 · NIGMS · GEORGETOWN UNIVERSITY · PI Patrick Alexander Forcelli, Anton Wellstein · 2022 to 2026
$1.3M
National Institute of Child Health and Human Development R01HD091994NICHD NIH HHS R01 HD091994NIGMS NIH HHS T32 GM142520NIGMS NIH HHS T32GM142520
6 · The paper itself

Abstract

backgroundPadsevonil (PSL) is a rationally designed anti-seizure medication (ASM) which has overlapping mechanisms of action with the two most common ASMs used for neonatal seizures, phenobarbital (PB) and levetiracetam (LEV). Here we evaluated the anti-seizure properties of PSL across the neonatal and adolescent period in rats in the pentlyenetetrazole (PTZ) induced seizures model.

methodsPostnatal day (P)7, P14 and P21 Sprague-Dawley rat pups were pre-treated with PSL (1-30 mg/kg), and assessed for seizure latency and severity 30 min later following injection of PTZ. A separate cohort of P7 pups were treated with neonatal ASMs and euthanized 24 h later (on P8) to assess induction of cell death, a feature common to many ASMs when given to P7 rodents. This effect has been extensively reported with PB, but not with LEV. Cell death was assessed by PathoGreen staining.

resultsPSL suppressed PTZ-evoked seizures across multiple age groups, particularly at higher doses, without producing increased cell death compared to vehicle. The effects of PSL were particularly notable at suppressing tonic-clonic seizure manifestations (82% of P7 and 100% of P14 and P21 animals were protected from tonic-clonic seizures with the 30 mg/kg dose).

conclusionsPSL displayed dose-dependent anti-seizure effects in immature rodents in the PTZ model of seizures in immature rats. While many ASMs, including PB, induce cell death in neonatal rats, PSL does not. This suggests that PSL may offer therapeutic benefit and a favorable safety profile for the treatment of neonatal seizures.

Indexed as

Animals, NewbornAnticonvulsantsCell DeathRats, Sprague-DawleySeizuresAnimalsCinnamatesDisease Models, AnimalDose-Response Relationship, DrugFemaleMalePentylenetetrazoleRatsAnticonvulsantsCinnamatesPentylenetetrazoleAnticonvulsantAntiepileptic drugAnti-seizure medicationApoptosisCell deathNeonatal seizureToxicology

Identifiers

PMID39028384
PMCPMC11584979

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

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 OpenQuestion graph.