Current Neuropharmacology最新文献

{"title":"Advances in Understanding Neuron-Microglia Interactions During Sciatic Nerve Injury and Regeneration.","authors":"Wei Zhang, Mei Liu, Ronghua Wu","doi":"10.2174/011570159X435745251229091943","DOIUrl":"https://doi.org/10.2174/011570159X435745251229091943","url":null,"abstract":"<p><p>The repair mechanisms following sciatic nerve injury involve complex signaling interactions between neurons and microglia. Recent studies have demonstrated that neurons activate microglia by releasing chemokines, glutamate, and neurotrophic factors. In turn, microglia regulate neuronal survival and regeneration via phagocytosis, phenotypic switching, and secretion of growth factors. However, the spatiotemporal diversity of signaling pathways, metabolic regulation of the microenvironment, and barriers to clinical application remain inadequately addressed. This review provides a comprehensive analysis of morphological and functional changes in neuronal cell bodies and of the activation and regulatory mechanisms of microglia after sciatic nerve injury. It highlights the dynamic interaction network encompassing the ATP-P2X7 signaling pathway, the CX3CL1- CX3CR1 pathway, the CCL2-CCR2 chemokine axis, the BDNF-TrkB pathway, and inflammatory mediators, offering novel insights into precision therapeutic strategies targeting neuron-glial interactions.</p>","PeriodicalId":10905,"journal":{"name":"Current Neuropharmacology","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147721940","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Innovative Approaches to Depression Therapy: The Antidepressant Efficacy and Mechanisms of General Anesthetics.","authors":"Xiangying Wei, Shan Xu, Zhaoqiong Zhu","doi":"10.2174/011570159X458197260226055817","DOIUrl":"https://doi.org/10.2174/011570159X458197260226055817","url":null,"abstract":"<p><p>Depression represents a critical global health burden, ranking as the second leading cause of disability worldwide. Although drug therapies remain an important cornerstone in treating depression, we must acknowledge their significant shortcomings: they often take too long to work, cause difficult side effects, and fail to prevent relapse. Critically, while current drugs target specific symptoms, the disorder itself stems from a far more complex interplay of genetic, environmental, and biological factors. Notably, emerging evidence indicates that several general anesthetics exhibit both rapid and sustained antidepressant effects. Ketamine, through blocking N-methyl-D-aspartate (NMDA) receptors, has established a new paradigm for rapid-acting antidepressant intervention. Building on this breakthrough, researchers are now finding that other agents, including propofol, isoflurane, and specific opioids, show promising results across preclinical and clinical settings. This expanding evidence base significantly advances the therapeutic scope of anesthesiology while addressing treatment-resistant depression(TRD) affecting approximately one-third of patients. This review examines intravenous/inhalational anesthetics and opioid analgesics for depression manage-ment, synthesizing contemporary preclinical and clinical evidence with particular focus on random-ized controlled trials and mechanistic studies. Our review highlights the specific biological changes that drive these effects. Beyond monoamine regulation, key factors include modulation of glutamate and GABA signals, which contribute to the restoration of synaptic plasticity in damaged brain circuits. Through combining what is known with what remains unclear, specifically focusing on dosing and long-term outcomes. We argue that targeting these mechanisms is key to creating new rapid antidepressants for patients who do not respond to standard care. Yet, success depends on balancing benefits against risks and establishing consistent treatment rules.</p>","PeriodicalId":10905,"journal":{"name":"Current Neuropharmacology","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147721890","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Potassium Channelopathies and Precision Medicine Approaches in Epilepsy: A Systematic Review of Personalized Treatment Strategies.","authors":"Changning Xie, Fei Yin, Miriam Kessi, Jing Peng","doi":"10.2174/011570159X407197251204124232","DOIUrl":"https://doi.org/10.2174/011570159X407197251204124232","url":null,"abstract":"<p><strong>Objective: </strong>This systematic review aimed to summarize recent progress in precision medicine for all studied potassium gene variants related to epilepsy. It analyzed studies conducted in cell and animal models and in humans.</p><p><strong>Methods: </strong>A comprehensive search was conducted on PubMed, Embase, and Cochrane databases for all years up to 2025.</p><p><strong>Results: </strong>Approximately 2257 papers were reviewed, but only 60 met the inclusion criteria: KCNT1 [n = 38], KCNQ2 [n = 10], KCNQ5 [n = 1], KCNB1 [n = 1], KCNA2 [n = 3], KCNA1 [n = 2], KCNA3 [n = 1], KCNT2 [n = 2], and KCNC1 [n = 2]. Therapies that appear effective for some patients with KCNT1 variants include quinidine, cannabidiol, fluoxetine, and carvedilol. Potential treatments supported by cell and/or animal models include bepridil and antisense oligonucleotide therapy. There is currently no precision therapy for KCNT2 variants; however, potential treatments supported by cell model evidence include quinidine, fluoxetine, loxapine, and riluzole. Emerging potential therapies for KCNQ2-related epilepsy include ezogabine, gabapentin, retigabine, donepezil, amitriptyline, linopirdine, pynegabine, SF0034, and XEN1101. Retigabine and gabapentin are potential therapies for KCNQ5 variants. Cannabidiol is a potential therapy for KCNB1 variants. 4-Aminopyridine is useful for KCNA1 and KCNA2 variants. Gapmer antisense oligonucleotides are a potential treatment for KCNA2 variants. Fluoxetine is a potential therapy for KCNA3 variants. Fluoxetine and compound RE01 are the potential therapies for KCNC1 variants.</p><p><strong>Conclusion: </strong>These studies collectively offer valuable insights into precision medicines for genetic epilepsy caused by pathogenic potassium variants. This review is essential because it informs clinical decision-making, including the selection of antiepileptic drugs, thereby supporting its integration into routine clinical care for this population. However, the low level of evidence and the heterogeneity of data from the included studies limit the review.</p>","PeriodicalId":10905,"journal":{"name":"Current Neuropharmacology","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147721881","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neuroinflammation in Spinal Cord Injury: Cellular and Molecular Mechanisms.","authors":"Xin Sun, Liyi Huang, Lu Wang, Lijuan Li, Hongxia Pan, Qing Zhang, Quan Wei","doi":"10.2174/011570159X419734251201070955","DOIUrl":"https://doi.org/10.2174/011570159X419734251201070955","url":null,"abstract":"<p><p>Traumatic spinal cord injury (SCI) elicits a coordinated cascade of innate and adaptive immune responses that evolve from the acute to the chronic phase and strongly influence regeneration and functional outcomes. This review synthesizes phase-specific pathobiology and the roles of microglia and infiltrating macrophages, astrocytes, neutrophils, dendritic cells, and T and B lymphocytes in neuroinflammation. We summarize glial heterogeneity beyond historical binary models, the dual actions of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6), and central signaling nodes such as NF-κB and the NLRP3 inflammasome. We also highlight how singlecell RNA sequencing and spatial transcriptomics reveal state-specific and region-specific immune programs and identify pathogenic and reparative circuits. These insights support precision immunomodulation tailored to injury stage, region, and cell state, including controlled attenuation of microglial overactivation while preserving debris clearance, redirection of reactive astrocyte states, and modulation of dendritic cell-T-cell crosstalk. Future research should prioritize validating causal immune nodes in vivo and developing biomarker-guided, stage-specific immunotherapies that limit secondary damage and improve neurological recovery after SCI.</p>","PeriodicalId":10905,"journal":{"name":"Current Neuropharmacology","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147721892","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The PI3K-AKT-VEGF Signaling Pathway Contributes to Doxorubicin-induced Chemotherapy-related Cognitive Impairment.","authors":"Xue-Chun Zhang, Ling-Chen Jiang, Jun-Xiao Song, Ji-Chao Peng, Ke Ni, Fu-Ming Shen, Can-Can Zhou","doi":"10.2174/011570159X414493251121073748","DOIUrl":"https://doi.org/10.2174/011570159X414493251121073748","url":null,"abstract":"<p><strong>Introduction: </strong>Chemotherapy-related cognitive impairment (CRCI) has been identified as one of the primary adverse effects of chemotherapy. Doxorubicin (DOX) is an anthracycline chemotherapeutic agent recognized as a fundamental component of chemotherapy. Nevertheless, limited research has been conducted to elucidate the neurotoxic mechanisms of DOX-mediated CRCI. We investigated the neurotoxic mechanisms of DOX by utilizing network toxicology and transcriptomic methods.</p><p><strong>Methods: </strong>DOX-induced CRCI animal models were successfully established. Spatial learning and memory were assessed using the Morris water maze (MWM) test. The levels of neuronal and synapserelated proteins in the cortex and hippocampus were detected. To elucidate the molecular mechanisms underlying DOX-induced neurotoxicity, an integrated approach combining network toxicology with transcriptomic profiling was employed. Lastly, the neurotherapeutic potential of LY294002 in relieving DOX-induced BBB disruption, neuronal cell loss, and cognitive impairment was evaluated.</p><p><strong>Results: </strong>Our findings demonstrate that DOX induces spatial learning and memory deficits and promotes neuronal cell loss, primarily by disrupting the blood-brain barrier (BBB) via the PI3K-AKT signaling pathway. Notably, we identified a significant upregulation of vascular endothelial growth factor (VEGF) within astrocytes in mice following DOX exposure.</p><p><strong>Discussion: </strong>Pharmacological inhibition of PI3K with LY294002 significantly reduced VEGF expression, mitigated BBB disruption and neuronal loss, and consequently alleviated DOX-associated cognitive impairment.</p><p><strong>Conclusion: </strong>DOX exerts neurotoxic effects by promoting VEGF oversecretion through the upregulation of the PI3K-AKT pathway. Inhibition of the PI3K-AKT pathway effectively mitigates these effects, thereby alleviating DOX-induced BBB disruption, neuronal cell loss, and cognitive impairment.</p>","PeriodicalId":10905,"journal":{"name":"Current Neuropharmacology","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147721938","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting HMGB1 to Attenuate Myocardial Ischaemia-reperfusion Injury (MIRI)-induced Cognitive Dysfunction.","authors":"Luyuan Yao, Ye Sun, Qinjun Chu, Jie Liu, Liya Li, Zhaoyang Xiao, Zhengyuan Xia","doi":"10.2174/011570159X453795260407092532","DOIUrl":"https://doi.org/10.2174/011570159X453795260407092532","url":null,"abstract":"<p><p>Myocardial Ischaemia-Reperfusion Injury (MIRI) is increasingly recognized as a contributor to cognitive dysfunction, with High-Mobility Group Box 1 (HMGB1) serving as a pivotal mediator in this heart-brain axis. Released from damaged cardiomyocytes, HMGB1 acts as a Damage-Associated Molecular Pattern (DAMP), activating Toll-Like Receptor 2/4 (TLR2/4) and the Receptor for Advanced Glycation End Products (RAGE), thereby triggering systemic inflamma-tion and neuroinflammation that disrupts Blood-Brain Barrier (BBB) integrity, promotes microglial activation, and induces synaptic dysfunction, ultimately leading to cognitive impairment. This article reviews recent studies on the role of HMGB1 in MIRI and cognitive dysfunction and aims to elucidate its potential interplay with the recently identified adipokine, Meteorin-like (Metrnl), which has also been shown to be critically involved in both MIRI and cognition; subsequently, the HMGB1/Metrnl functional antagonism may be a potential therapeutic mechanism for MIRI-induced cognitive impairment. Addressing the HMGB1/Metrnl interplay offers a pathway to mitigate the long-term disability and loss of independence associated with MIRI-induced cognitive impairment, potentially alleviating the substantial socioeconomic burden and caregiver strain that follows major cardiac events.</p>","PeriodicalId":10905,"journal":{"name":"Current Neuropharmacology","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147721915","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Blockade of Dopamine D2/3 Receptors Improves Neuronal Network Oscillations in Heterozygous Reeler Mice.","authors":"Guodong Wang, Zhenrong Li, Huimin Yang, WanLiu Wu, Hongxing Zhang, Chengbiao Lu","doi":"10.2174/011570159X423035251129093058","DOIUrl":"https://doi.org/10.2174/011570159X423035251129093058","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Introduction: &lt;/strong&gt;Schizophrenia (SCZ) is a severe mental illness characterized by polygenic abnormalities, neural network dysfunction, and cognitive impairment. Mice with reelin gene deficiency (heterozygous reeler mice, HRM) exhibit social withdrawal and dysregulated neurotransmitter systems, including dopamine (DA), similar to abnormalities observed in SCZ patients; therefore, HRM are regarded as a relevant animal model of SCZ. Neural network oscillations in the gamma frequency band (30-100 Hz; γ oscillations) play a crucial role in information processing and neural synchronization in the brain, and disrupted γ oscillations are a hallmark of SCZ. Our previous work showed dysregulated DA modulation of hippocampal γ oscillations in HRM, although the underlying mechanisms remained unclear. In this study, we examined the effects of various DA receptor (DR) agonists and antagonists on hippocampal γ oscillations in wild-type (WT) and HRM to identify mechanisms that may restore DA-dependent modulation of neural network activity in HRM.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Behavioral performance was assessed using the elevated plus maze (EPM), open field test (OFT), Morris water maze (MWM), and three-chamber social interaction test. Local field potential (LFP) recordings were used to monitor hippocampal CA3 γ oscillations. Western blotting was performed to quantify expression levels of DA receptor subunits.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Behavioral tests revealed that HRM displayed reduced social interaction and impaired social novelty preference (three-chamber test), fewer entries and reduced time spent in the open arms (EPM), while maintaining normal motor activity (OFT) and learning and memory abilities (MWM). These findings suggest that HRM exhibit anxiety-like behaviors and deficits in social interaction. LFP recordings showed that the D1R agonist (SKF-81297) and D2R agonist (Quinpirole) increased γ-oscillation power (γ power) in WT mice but had no effect in HRM. The D3R agonist (PD- 128907) did not alter γ power in either genotype. The D4R agonist (PD-168077) caused a modest increase in γ power in HRM. Notably, the D3R antagonist (GR103691) and the D2R antagonist (Phenothiazine), but not the D1R antagonist (SKF-83566) or the D4R antagonist (L-745870), significantly enhanced γ power in HRM. Western blot analysis revealed upregulated D3R expression in the hippocampus of HRM, while D1R, D2R, and D4R levels remained comparable to WT.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Discussion: &lt;/strong&gt;HRM exhibits disrupted dopaminergic modulation of γ oscillations, likely due to impaired D1R/D2R signaling combined with elevated D3R expression. Pharmacological blockade of D3R and, to some extent, D2R effectively restores γ-oscillation modulation in HRM, highlighting the critical role of these receptors in SCZ-related network dysfunction.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;Our findings demonstrate that selective blockade of D2/3 receptors restores DAdependent neuronal netw","PeriodicalId":10905,"journal":{"name":"Current Neuropharmacology","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147721908","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring Risk Drugs and Mechanisms in Dystonia: Insights from Pharmacovigilance and Proteogenomics.","authors":"Zhiqing Chen, Jingyi Yao, Jingqi Lin, Huaiyu Sun, Jiaai Li, Wuqiong Zhang, Hongmei Meng, Shuai Hou","doi":"10.2174/011570159X448484260107125041","DOIUrl":"https://doi.org/10.2174/011570159X448484260107125041","url":null,"abstract":"<p><strong>Introduction: </strong>Dystonia is a movement disorder (MD), which is the third most common MD after Parkinson's disease and essential tremor. Although drugs are one of the main risk factors for dystonia, they are often not fully recognized. This study aims to identify drugs related to dystonia and explore the potential molecular mechanism of drug-induced dystonia.</p><p><strong>Methods: </strong>We used disproportionality analysis to analyze the data of the FDA Adverse Event Reporting System (FAERS) to identify risk drugs associated with dystonia. The molecular target information of these drugs comes from the DrugBank database. In order to explore the causal relationship, we integrated proteomics data from deCODE research and the UK Biobank Pharma Proteomics Project with the genome-wide association study data from FinnGen to carry out proteome-wide Mendelian randomization (MR) analysis. The application of Bayesian colocalization analysis enhances the reliability of causal inference. In addition, we have built a protein-protein interaction (PPI) network to examine the relationship between dystonia-related proteins and drug target genes.</p><p><strong>Results: </strong>We found that in the reports of 18,286 cases of dystonia, 84 drugs showed continuous positive pharmacovigilance signals. The top 30 drugs are mainly antipsychotics and antidepressants. Metoclopramide has the strongest correlation, followed by prochlorperazine, haloperidol, and ziprasidone. MR and colocalization analysis identified 58 proteins related to susceptibility to dys-tonia, of which 6 were verified in different cohorts. PPI analysis revealed that 21 dystonia-related genes interacted with 22 drug target genes, which are enriched in neuronal signaling pathways, metabolic regulation, and xenobiotic metabolism.</p><p><strong>Discussion: </strong>This integrated framework transcends traditional pharmacovigilance because it combines real-world drug safety data with causal inference of proteogenomics. For the first time, we have constructed a proteogenomic map of drug-induced dystonia. Starting from the drug-disease relationship, we deeply explored the causal mechanisms, such as dopamine-cholinergic imbalance, thus providing mechanism-level insights for drug-induced susceptibility.</p><p><strong>Conclusion: </strong>Our study highlights risk drugs for dystonia and their molecular mechanisms and provides evidence for the safer and more individualized use of antipsychotics, antidepressants, and other drugs related to dystonia.</p>","PeriodicalId":10905,"journal":{"name":"Current Neuropharmacology","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147765246","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In Silico Design and Evaluation of Diosmin Analogs for Targeting Peroxisome Proliferator-activated Receptor γ (PPAR-γ) Against Alzheimer's Disease.","authors":"Yilu Sun, Tin Wing Chan, Weiyao Liao, Minxi Li, Xiaowen Mao, Yibin Feng, Jianhui Rong, Jia Zhao","doi":"10.2174/011570159X453424260218065734","DOIUrl":"https://doi.org/10.2174/011570159X453424260218065734","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is a neurodegenerative disorder characterized by progressively declining cognitive abilities and memory impairment. This disease increasingly challenges the quality of life and health of the elderly population, underscoring the need for effective therapeutic strategies. The existing anti-AD medications are designed to improve symptoms but not to cure the disease. Novel drugs are urgently needed to target the specific mechanisms that mediate disease progression. Peroxisome proliferator-activated receptor gamma (PPAR-γ) is a potential target for the development of anti-AD therapies. Through virtual screening of natural PPAR-γ ligands, the flavonoid diosmin was found to bind to PPAR-γ with high potency. This study exploited diosmin as a lead compound to design a panel of diosmin analogs via chemical modifications for better biological efficacy in targeting PPAR-γ. These diosmin analogs were evaluated using in silico approaches, including molecular docking, absorption, distribution, metabolism, and excretion (ADME) predictions, and molecular dynamics (MD) simulations. As a result, molecular docking identified 12 di-osmin analogs with better binding affinity to PPAR-γ compared with diosmin. ADME and MD analyses demonstrated that S1DhP1 exhibited lower binding free energy, better water solubility, and stability than diosmin. Thus, this study provides important information via in silico approaches and hypotheses, suggesting S1DhP1 as a promising PPAR-γ agonist for the treatment of AD that warrants further experimental validation.</p>","PeriodicalId":10905,"journal":{"name":"Current Neuropharmacology","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147765218","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"From Analgesia to Synaptic Remodeling: A Systematic Review of Acetaminophen's Neuromodulatory Effects.","authors":"Naser-Aldin Lashgari, Negar Bayan, Maryam Abbasi-Kashkooli, Arvin Memari, Nazanin Momeni Roudsari, Hamed Shafaroodi","doi":"10.2174/011570159X430226260314153211","DOIUrl":"https://doi.org/10.2174/011570159X430226260314153211","url":null,"abstract":"<p><strong>Introduction: </strong>Neuro-related disorders will be rising globally. Current treatments have numerous limitations that can impair patients' quality of life. One of the key therapeutic approaches is promoting neuroplasticity. Neuroplasticity plays a vital role in memory, learning, and recovery of function after neural damage. Acetaminophen (Paracetamol; APAP) has been suggested as a neuroprotective treatment through modulation of neuroplasticity dose-duration dependently.</p><p><strong>Methods: </strong>This systematic review was conducted across major databases such as PubMed/MEDLINE, Google Scholar, Scopus, and Web of Science, between 2002 and October 2025, and from an initial pool of 537 articles, we selected only English-language studies with complete methodology and full results reporting the effects of acetaminophen on neuroplasticity.</p><p><strong>Results: </strong>Preclinical evidence suggests that short-term, low-dose acetaminophen can have neuroprotective effects. Acetaminophen is metabolized in the brain to AM404, which activates TRPV1, inhibit COX-1/COX-2, and modulates the endocannabinoid system, reducing inflammation and oxidative stress. They also engage BDNF neurotrophic signalling, creating a mechanistic basis for potential neuroplasticity modulation.</p><p><strong>Discussion: </strong>While low-dose, short-term acetaminophen shows neuroprotective effects in preclinical models, long-term or high-dose use may lead to neurotoxicity.</p><p><strong>Conclusion: </strong>Although preclinical evidence suggests that acetaminophen may influence neuroplasticity in a dose- and time-dependent manner, substantial heterogeneity in dosing protocols limits definitive conclusions. Therefore, further standardized preclinical and clinical studies with larger sample sizes and longer follow-up are required to define safe and effective exposure windows in humans.</p>","PeriodicalId":10905,"journal":{"name":"Current Neuropharmacology","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147671089","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}