Evidence map›Paper›PMID 41396383›Full record

ArticleForensic toxicology2026

Inactivation of calcium Ion signaling in neuronal SK-N-SH cells with development of resistance to a designer drug α-pyrrolidinooctanophenone.

Yuji Sakai, Yoshifumi Morikawa, Toshihiro Matsumura, Shunsuke Jimbo, Koichi Suenami, Gento Yamashita, Atsushi Nagai, Tomomi Michiue, Akira Ikari, Toshiyuki Matsunaga

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Article in Forensic toxicology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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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

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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

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

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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

10 authors.

Yuji SakaiForensic Science Laboratory, Gifu Prefectural Police Headquarters, Gifu, 500-8501, Japan. yujsakai1115@gmail.com.ORCID 0009-0005-2796-6133
Yoshifumi MorikawaForensic Science Laboratory, Gifu Prefectural Police Headquarters, Gifu, 500-8501, Japan.
Toshihiro MatsumuraLaboratory of Bioinformatics, Gifu Pharmaceutical University, Gifu, 502-8585, Japan.
Shunsuke JimboForensic Science Laboratory, Gifu Prefectural Police Headquarters, Gifu, 500-8501, Japan.
Koichi SuenamiForensic Science Laboratory, Gifu Prefectural Police Headquarters, Gifu, 500-8501, Japan.
Gento YamashitaLaboratory of Bioinformatics, Gifu Pharmaceutical University, Gifu, 502-8585, Japan.
Atsushi NagaiDepartment of Legal Medicine, Graduate School of Medicine, Gifu University, Gifu, 501-1194, Japan.
Tomomi MichiueDepartment of Legal Medicine, Graduate School of Medicine, Gifu University, Gifu, 501-1194, Japan.
Akira IkariLaboratory of Biochemistry, Gifu Pharmaceutical University, Gifu, 501-1196, Japan.
Toshiyuki MatsunagaLaboratory of Bioinformatics, Gifu Pharmaceutical University, Gifu, 502-8585, Japan.

Funding

Japan Society for the Promotion of Science 24K20257
6 · The paper itself

Abstract

purposeThe cellular mechanisms underlying tolerance development to psychostimulant-induced neurotoxicity remain poorly understood. This study investigated these mechanisms using pyrrolidinophenone derivatives (PPs), potent amphetamine-type stimulants with strong dopaminergic activity and high cytotoxicity, aiming to establish a neuronal tolerance model and to explore adaptive processes relevant to substance use disorder.

methodsHuman SK-N-SH neuronal cells were chronically exposed to α-pyrrolidinooctanophenone (α-POP) to prepare the drug-resistant cell line, SH/POP. Transcriptomic profiling was performed to identify gene expression alterations associated with tolerance development.

resultsCell sensitivity assay showed that SH/POP cells can survive at lethal concentrations (> 40 μM) of α-POP. RNA sequence analysis of the resistant cells identified alterations in 1,298 differentially expressed genes and the gene ontology analysis surmised an upregulation of calcium-binding-related genes. The development of α-POP resistance reduced the basal Ca

conclusionsResistance development of neuronal cells to PPs is ascribable to suppression of calcium-dependent apoptosis and CREB signaling, and constitutive activation of endoplasmic reticulum stress responses. The SH/POP cell line represents a novel in vitro model to study molecular adaptations to psychostimulant toxicity and provides insights into neuroadaptive mechanisms underlying substance use disorder.

Indexed as

Calcium SignalingCentral Nervous System StimulantsDesigner DrugsDrug ResistanceNeuronsPyrrolidinesCaspase 3Cell Line, TumorCyclic AMP Response Element-Binding ProteinGene Expression ProfilingHumansProto-Oncogene MasCaspase 3Central Nervous System StimulantsCyclic AMP Response Element-Binding ProteinDesigner DrugsMAS1 protein, humanProto-Oncogene MasPyrrolidinesCalcium releaseCREBDrug resistanceER stressNeuronal cellα-Pyrrolidinooctanophenone

Identifiers

PMID41396383

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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 OpenQuestion graph.