Evidence map›Paper›PMID 33025394›Full record

ArticlePharmacological reports : PR2021

Polygonogram with isobolographic synergy for three-drug combinations of phenobarbital with second-generation antiepileptic drugs in the tonic-clonic seizure model in mice.

Jarogniew J Łuszczki, Dominika Podgórska, Justyna Kozińska, Marek Jankiewicz, Zbigniew Plewa, Mateusz Kominek, Dorota Żółkowska, Magdalena Florek-Łuszczki

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In one paragraph

Article in Pharmacological reports : PR, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
0.6field-weighted citation impact, top 32% of its field
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

5 citing papers in PubMed, 8 citations in OpenAlex.

  1. Article
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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

8 authors at 4 institutions in 2 countries.

Jarogniew J ŁuszczkiDepartment of Pathophysiology, Medical University, Jaczewskiego 8b, 20-090, Lublin, PL, Poland. jarogniew.luszczki@umlub.pl.ORCID http://orcid.org/0000-0002-3059-0393
Dominika PodgórskaDepartment of Pathophysiology, Medical University, Jaczewskiego 8b, 20-090, Lublin, PL, Poland.
Justyna KozińskaChair and Clinic of Hematooncology and Bone Marrow Transplantation, Medical University, Lublin, Poland.ORCID http://orcid.org/0000-0001-8817-5638
Marek JankiewiczChair and Clinic of Cardiology, Medical University, Lublin, Poland.ORCID https://orcid.org/0000-0001-9900-9168
Zbigniew PlewaDepartment of General, Oncological and Minimally Invasive Surgery, 1st Military Clinical Hospital, Lublin, Poland.ORCID http://orcid.org/0000-0001-6255-5085
Mateusz KominekClinic of Orthopedics and Traumatology, Medical University, Lublin, Poland.ORCID http://orcid.org/0000-0003-4591-6752
Dorota ŻółkowskaDepartment of Neurology, School of Medicine, University of California-Davis, Sacramento, CA, USA.ORCID http://orcid.org/0000-0003-1988-0119
Magdalena Florek-ŁuszczkiDepartment of Medical Anthropology, Institute of Rural Health, Lublin, Poland.ORCID http://orcid.org/0000-0003-1489-2399
Medical University of Lublin · PL1 Military Clinical Hospital with Outpatient Clinic · PLInstytut Medycyny Wsi im. Witolda Chodźki · PLUniversity of California, Davis · US

Funding

Uniwersytet Medyczny w Lublinie DS 474 / 2012-2015
6 · The paper itself

Abstract

backgroundCombination therapy consisting of two or more antiepileptic drugs (AEDs) is usually prescribed for patients with refractory epilepsy. The drug-drug interactions, which may occur among currently available AEDs, are the principal criterion taken by physicians when prescribing the AED combination to the patients. Unfortunately, the number of possible three-drug combinations tremendously increases along with the clinical approval of novel AEDs.

aimTo isobolographically characterize three-drug interactions of phenobarbital (PB) with lamotrigine (LTG), oxcarbazepine (OXC), pregabalin (PGB) and topiramate (TPM), the maximal electroshock-induced (MES) seizure model was used in male albino Swiss mice. MATERIALS AND

methodThe MES-induced seizures in mice were generated by alternating current delivered via auricular electrodes. To classify interactions for 6 various three-drug combinations of AEDs (i.e., PB + TPM + PGB, PB + OXC + TPM, PB + LTG + TPM, PB + OXC + PGB, PB + LTG + PGB and PB + LTG + OXC), the type I isobolographic analysis was used. Total brain concentrations of PB were measured by fluorescent polarization immunoassay technique.

resultsThe three-drug mixtures of PB + TPM + PGB, PB + OXC + TPM, PB + LTG + TPM, PB + OXC + PGB, PB + LTG + PGB and PB + LTG + OXC protected the male albino Swiss mice from MES-induced seizures. All the observed interactions in this seizure model were supra-additive (synergistic) (p < 0.001), except for the combination of PB + LTG + OXC, which was additive. It was unable to show the impact of the studied second-generation AEDs on total brain content of PB in mice.

conclusionsThe synergistic interactions among PB and LTG, OXC, PGB and TPM in the mouse MES model are worthy of being transferred to clinical trials, especially for the patients with drug resistant epilepsy, who would benefit these treatment options.

Indexed as

AnimalsAnticonvulsantsBrainDrug SynergismDrug Therapy, CombinationElectroshockEpilepsy, Tonic-ClonicMaleMicePhenobarbitalSeizuresAnticonvulsantsPhenobarbitalAntiepileptic drugsDrug interactionsDrug synergismIsobolographic analysisMaximal electroshock

Identifiers

PMID33025394
PMCPMC7862539
OpenAlexW3092538801

What OpenQuestion holds

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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.