Naunyn-Schmiedeberg's archives of pharmacology最新文献

{"title":"Combined rituximab and magnesium acetyl taurate therapy attenuates neurodegeneration via ERK/c-JNK/P38MAPK signaling modulation in methylmercury-induced amyotrophic lateral sclerosis-like neurotoxicity.","authors":"Trina Saha, Sidharth Mehan","doi":"10.1007/s00210-026-05948-9","DOIUrl":"https://doi.org/10.1007/s00210-026-05948-9","url":null,"abstract":"<p><p>Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder characterized by motor neuron degeneration, oxidative stress, neuroinflammation, mitochondrial dysfunction, and dysregulation of intracellular signaling pathways. The present study investigated the neuroprotective potential of rituximab (RTXMB), alone and in combination with magnesium acetyl taurate (MACT600), against methylmercury (MLMC5)-induced ALS-like pathology in adult Wistar rats through modulation of the ERK/c-JNK/P38MAPK signaling pathway. ALS was induced by oral administration of MLMC5 (5 mg/kg) for 21 days. RTXMB (50 and 100 mg/kg) and MACT600 (600 mg/kg) treatments were administered from day 22 to day 42. Behavioral assessments, neurochemical estimations, ELISA, Western blotting, hematological analysis, gross morphology, and histopathological evaluations were performed. MLMC5 exposure produced significant impairments in locomotion, muscular strength, cognition, and emotional behavior, accompanied by increased oxidative stress, inflammatory cytokines, glutamate excitotoxicity, apoptotic markers, methylmercury accumulation, and dysregulation of ERK/c-JNK/P38MAPK signaling. Moreover, MLMC5 caused marked demyelination, neuronal degeneration, neurotransmitter imbalance, skeletal muscle damage, and hematological dysfunction. RTXMB treatment significantly attenuated these pathological alterations in a dose-dependent manner, with RTXMB100 showing greater neuroprotective efficacy. Combined administration of RTXMB100 and MACT600 demonstrated the most pronounced therapeutic effects by restoring antioxidant defenses, suppressing neuroinflammation and apoptosis, normalizing neurotransmitter levels, preserving myelin integrity, and improving neuronal morphology. The findings suggest that RTXMB, particularly in combination with MACT600, exerts potent neuroprotective effects against ALS-like pathology via modulation of MAPK signaling pathways and may represent a promising therapeutic strategy for ALS management.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149170131","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The global surge of cocaine use disorder: a 30-year burden analysis from the GBD 2021.","authors":"Zhuping Ren, Xinhui Wu, Jing Chen, Xiaoli Li","doi":"10.1007/s00210-026-05992-5","DOIUrl":"https://doi.org/10.1007/s00210-026-05992-5","url":null,"abstract":"<p><p>Cocaine use disorder (CUD) represents a growing global health challenge with an inadequately characterized epidemiological profile. Utilizing data from the Global Burden of Disease (GBD) 2021 study across 204 countries or territories (1990-2021), this study assessed age-standardized incidence (ASIR), prevalence (ASPR), mortality (ASMR), and disability-adjusted life years (DALYs) rates. Key trends were analyzed using Estimated Annual Percentage Change (EAPC). Additional analyses included frontier mapping against the Socio-demographic Index (SDI), decomposition to identify driving factors, and ARIMA modeling for future projections. Findings revealed that global cocaine production tripled between 2009 and 2023, coinciding with a rising CUD burden: ASMR increased by 114% from 1990 to 2021, with males experiencing a faster mortality increase compared to females. High-income and Latin American regions bore the highest burden-the USA led in ASIR and ASMR, while Spain saw declines after 2005 due to stringent policies. SDI strongly correlated with ASIR (ρ = 0.59), and high-SDI regions had higher DALYs than low-SDI areas. Projections indicate accelerating ASMR and DALY rates in high-income countries by 2036. CUD imposes an escalating and inequitable global burden, disproportionately affecting males, high-income populations, and the Americas. Addressing this crisis requires targeted interventions and improved surveillance of evolving use patterns and comorbidities.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149170022","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of vitamin B1/B6/B12 complex on methotrexate-induced hepatorenal toxicity in a short-term acute rat model.","authors":"Ayça Toprak-Semiz, Esra Deniz, Atilla Topçu, Sibel Mataracı Karakaş, Çiğdem Öztürk, Efsane Yavuz-Bedir","doi":"10.1007/s00210-026-05993-4","DOIUrl":"https://doi.org/10.1007/s00210-026-05993-4","url":null,"abstract":"<p><p>This study evaluated the effects of vitamin B1/B6/B12 complex supplementation on methotrexate (MTX)-induced hepatorenal injury in a short-term, single-dose acute rat model. Male Wistar rats were assigned to control, MTX, low-dose (MTX + VB-L), and high-dose (MTX + VB-H) vitamin B complex groups. A single MTX (20 mg/kg) was administered intraperitoneally on day 7. Vitamin B1/B6/B12 was administered intraperitoneally daily at 16/16/0.16 or 32/32/0.32 mg/kg on days 1-14. Samples were collected on day 14. Serum AST, ALT, urea, and creatinine, hepatic, and renal thiobarbituric acid reactive substances (TBARS) and total thiol (TT), and histopathological changes were evaluated. MTX significantly increased AST, urea, creatinine, hepatic and renal TBARS, and multiple histopathological scores compared with controls. Compared with MTX alone, AST and hepatic TBARS were significantly lower only in the MTX + VB-H group, whereas creatinine and renal TBARS were significantly lower in both treatment groups. Renal TBARS was significantly lower in MTX + VB-L than in MTX + VB-H. Neither the treatment group differed significantly from the MTX group in ALT, urea, TT, or any hepatic or renal histopathological parameter. Vitamin B complex co-administration was associated with improvements in selected biochemical markers and lower TBARS levels, without statistically significant histopathological improvement. The absence of a vitamin-only group limits distinction between MTX-specific attenuation and independent formulation effects. Further preclinical studies are required before clinical implications can be established.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149170496","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mapping the knowledge landscape and identifying frontiers of mitochondrial dysfunction in sepsis-associated acute kidney injury: a four-decade bibliometric and visualized analysis.","authors":"Cai-Xia Sun, Yun-Sheng Liu, Zeng-Wei Kou, Han Tang","doi":"10.1007/s00210-026-05984-5","DOIUrl":"https://doi.org/10.1007/s00210-026-05984-5","url":null,"abstract":"<p><p>Mitochondrial dysfunction has been recognized as a central pathogenic event and is under active investigation as a candidate therapeutic target in sepsis-associated acute kidney injury (SA-AKI). This study aims to employ multi-tool bibliometric analysis to systematically map the four-decade intellectual landscape of this field, thereby identifying emerging research hotspots and outlining priority-setting directions for future pharmacological investigation. Because publication and citation metrics quantify scholarly attention rather than therapeutic efficacy, the pathways highlighted here reflect research trends and priority-setting signals, not established therapeutic targets. A comprehensive literature retrieval was conducted across PubMed, Web of Science, and Scopus up to March 18, 2026. Following rigorous data cleaning, 837 publications were analyzed using CiteSpace, VOSviewer, and the bibliometrix R package to visually evaluate publication trends, knowledge networks, and evolving research hotspots. Cumulative publication output exhibits sustained exponential growth (R² = 0.997), accelerating significantly post-2010. China and the USA dominate global productivity, though institutional collaboration networks reveal pronounced regional clustering. Notably, publication hubs have transitioned significantly from traditional critical care journals to molecular and pharmacological journals, consistent with a shifting emphasis of scholarly attention toward molecular and pharmacological research themes. Keyword and citation burst analyses suggest that the research frontier has evolved from broad physiological observations to specific subcellular executioners. Mitochondria-mediated programmed cell death (apoptosis, pyroptosis, and ferroptosis) and oxidative stress have become the most prominent bibliometric hotspots and candidate pharmacological targets. The field of SA-AKI research has shown a pronounced, publication-driven shift from clinical phenotyping to the target-driven molecular deconstruction of mitochondrial damage; we emphasize that this result reflects research priorities, not proven therapeutic efficacy of these targets. To overcome current translational bottlenecks and off-target effects of existing agents, future drug development should transition from isolated in vitro models toward clinical multi-omics validation. Developing innovative targeted delivery systems (such as engineered nanomaterials and exosomes) and multi-target synergistic therapies will need rigorous empirical testing to determine whether they can precisely mitigate the complex SA-AKI \"mitochondrial storm\".</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149169965","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association of 24-hours net positive fluid balance with log-transformed vancomycin trough concentrations in the early phase of therapy among critically ill patients.","authors":"Azfar Athar Ishaqui, Khalid Orayj, Tauqeer Hussain Mallhi, Salman Ashfaq Ahmad, Sultan M Alshahrani, Rayah Asiri, Adnan Iqbal, Asaad Ahmed Asaad Khalil, Mohammed Ali Kaddoura, Muhammad Bilal Maqsood, Javeria Farooq, Narendar Kumar","doi":"10.1007/s00210-026-05974-7","DOIUrl":"https://doi.org/10.1007/s00210-026-05974-7","url":null,"abstract":"<p><p>Early vancomycin troughs are frequently low in critical illness and fluid accumulation may contribute through distribution effects. This study estimated the association between net positive fluid balance and early vancomycin troughs as a hypothesis-generating analysis and explored variation across early-therapy windows and by hypoalbuminemia. A retrospective cohort study used ICU electronic health record data from MIMIC-IV. ICU stays with a timing-validated trough were included. The primary cohort N = 255 required at least 80% EMAR dose capture in the prior 24 h and delta serum creatinine at or below 0.2 mg/dL across the 48 h before trough and trough within 72 h of first IV dose. Net fluid balance in the prior 24 h was modeled per + 5 L. Outcome was log trough. Models adjusted for serum creatinine and administered dose and administration count in the prior 24 h. Sensitivity windows were within 48 h (N = 162) and within 96 h (N = 289). Hypoalbuminemia below 3 g/dL was explored in the measured subset. Median trough was 14.00 mg/L (IQR 10.15 to 18.15) and 62 of 255 were below 10 mg/L (24.3%). The point estimate suggested an 11.7% lower trough concentration per + 5 L net positive balance (β =  - 0.1247; SE = 0.079; p = 0.115), but the 95% CI (- 24.4% to + 3.1%) included no association. Serum creatinine had a positive coefficient (β = 0.2995; p = 0.061). Point estimates were similar across early-therapy windows with all confidence intervals including no association. The exploratory albumin interaction was imprecise and limited by substantial missingness and small subgroup sizes. The point estimate suggested lower early vancomycin troughs with higher net positive fluid balance, but the confidence interval included no association. These hypothesis-generating findings require prospective validation to clarify whether fluid balance is associated with early trough concentrations and area under the curve exposure.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149165104","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Retraction Note: Cardioprotective role of GTS-21 by attenuating the TLR4/NF-κB pathway in streptozotocin-induced diabetic cardiomyopathy in rats.","authors":"Mahmoud E Youssef, Heba M Abdelrazek, Yasser M Moustafa","doi":"10.1007/s00210-026-05995-2","DOIUrl":"https://doi.org/10.1007/s00210-026-05995-2","url":null,"abstract":"","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149169944","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tirofiban after intravenous thrombolysis in acute ischemic stroke patients: An updated systematic review and meta-analysis of randomized controlled trials.","authors":"Omar Fayez Abbas, Abdullah Almarfadi, Nour Aldin Tarek Ahmed, Aya Magdy Siam, Roaa Haddad, Fatma Aljalawy, Ahmed Harb, Abdelrahman M Hamouda, R Saha, Sherief Ghozy, Adam A Dmytriw","doi":"10.1007/s00210-026-05950-1","DOIUrl":"https://doi.org/10.1007/s00210-026-05950-1","url":null,"abstract":"<p><p>Early antiplatelet therapy after intravenous thrombolysis (IVT) for acute ischemic stroke remains controversial because of concerns regarding hemorrhagic complications. Tirofiban, a reversible glycoprotein IIb/IIIa receptor antagonist, may reduce platelet-mediated rethrombosis and improve reperfusion after thrombolysis. We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) evaluating the efficacy and safety of early intravenous tirofiban following IVT. PubMed, Scopus, Web of Science, and the Cochrane Library were searched from inception through May 2026. RCTs comparing early intravenous tirofiban versus standard care or placebo after IVT were included. Outcomes included functional independence (modified Rankin Scale [mRS] 0-2), excellent outcome (mRS 0-1), symptomatic intracranial hemorrhage (sICH), any intracranial hemorrhage (ICH), and 90-day mortality. Risk ratios (RRs) with 95% confidence intervals (CIs) were pooled using random-effects models. Six randomized controlled trials (RCTs) involving 1787 patients were included. Tirofiban significantly increased the likelihood of achieving functional independence at 90 days (RR, 1.14; 95% CI, 1.03-1.25; P = 0.019). Although tirofiban showed a trend toward improving excellent functional outcome, the difference was not statistically significant (RR, 1.21; 95% CI, 0.95-1.56; P = 0.080). No significant differences were observed in symptomatic intracranial hemorrhage (RR, 1.72; 95% CI, 0.57-5.19; P = 0.265), any intracranial hemorrhage (RR, 1.17; 95% CI, 0.72-1.90; P = 0.453), or 90-day mortality (RR, 0.92; 95% CI, 0.59-1.45; P = 0.668). Sensitivity analyses demonstrated robust findings across all outcomes. Early intravenous tirofiban following thrombolysis was associated with improved functional recovery without a significant increase in mortality or intracranial hemorrhage on a relative scale. Although a 1% absolute increase in symptomatic ICH was observed, the difference was not statistically significant. These findings support further investigation of tirofiban as an adjunct to thrombolysis in selected patients with acute ischemic stroke.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149170089","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Deciphering the mechanisms of resveratrol in knee osteoarthritis treatment: insights from bioinformatics and experimental validation.","authors":"Chenyi Huang, Xiong Ye, Xing Liu, Fei Liu, Yang Li, Xi Chen, Pandeng Hao, Xubing San","doi":"10.1007/s00210-026-05985-4","DOIUrl":"https://doi.org/10.1007/s00210-026-05985-4","url":null,"abstract":"&lt;p&gt;&lt;p&gt;Knee osteoarthritis (KOA) is the most prevalent chronic joint disorder in orthopedics, with its underlying pathogenic genes and effective treatment methods remaining unclear. Resveratrol (RES), a potent bioactive natural polyphenol, has been shown to effectively alleviate KOA; however, its complex regulatory mechanisms require further investigation. This research seeks to clarify the molecular mechanisms by which RES contributes to the treatment of KOA, utilizing a blend of bioinformatics approaches and experimental validation. First, gene expression profiles related to KOA were obtained from the GEO database. Subsequently, differential gene analysis was conducted on the samples, and modular genes linked to KOA were extracted through the application of a weighted gene co-expression network. The LASSO algorithm was utilized to identify crucial pathogenic genes in KOA, which were later confirmed using clinical samples. Targets for RES were sourced from traditional Chinese medicine databases, and the therapeutic targets for KOA treatment were determined by finding the intersection of these sources. An enrichment analysis was carried out based on the therapeutic targets identified. Molecular docking studies were conducted to further assess the binding affinity of key therapeutic genes with RES. Lastly, animal experiments were implemented to substantiate the molecular mechanisms by which RES acts in the treatment of KOA. We identified 460 module genes and 10 key predictive genes through LASSO analysis. The findings from the enrichment analysis concerning potential therapeutic targets for RES in the treatment of KOA reveal that the significant genes implicated include VEGFA, IL6, MAPK3, IL1B, CASP3, and AKT1. Subsequent validation with clinical samples revealed that IL6, MAPK3, IL1B, CASP3, and AKT1 were significantly elevated during the progression of KOA, while VEGFA was markedly reduced in the context of KOA. The outcomes of the GO and KEGG analyses suggest that the primary biological processes implicated encompass apoptosis, the FoxO signaling pathway, the IL-17 signaling pathway, cellular senescence, and the NF-κB signaling pathway. The findings from the immune infiltration analysis indicate that resting CD4 memory T cells, memory B cells, resting mast cells, eosinophils, and activated mast cells may have important functions in the immune mechanisms related to KOA. The results of animal experiments demonstrate that RES effectively inhibits the expression of inflammatory factors such as IL-6, MAPK3, IL-1β, CASP3, and AKT1 during the progression of KOA, promotes the expression of VEGFA, and concurrently suppresses the FoxO signaling pathway and the IL-17 signaling pathway, thereby reducing cartilage damage induced by MIA and delaying the progression of KOA. In summary, RES can regulate the expression of genes including VEGFA, IL-6, MAPK3, IL-1β, CASP3, and AKT1, inhibit the FoxO signaling pathway and the IL-17 signaling pathway, alleviate cart","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149167587","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmacological features of mesoionic compounds: antitumoral effects and bioenergetic disruption of sydnones and 1,3,4-thiadiazolium derivatives.","authors":"André Felipe Naidek, Mariane Londero Rodrigues, Maria Carolina Stipp, Douglas de Jesus da Silva Claudino, Aurea Echevarria, Silvia Suter Correia Cadena, Alexandra Acco","doi":"10.1007/s00210-026-05970-x","DOIUrl":"https://doi.org/10.1007/s00210-026-05970-x","url":null,"abstract":"<p><p>Mesoionic compounds are five-membered heterocyclic betaines that cannot be satisfactorily represented by a single covalent or polar structure. Because their positive and negative charges are delocalized over separate regions of the ring, they yield a net-neutral molecule with a high dipole moment. This unique electronic configuration confers amphiphilic character and pronounced affinity for biological membranes, including mitochondria, underlying a broad pharmacological profile that includes antitumoral, anti-inflammatory and analgesic activities. Among the several mesoionic scaffolds, sydnones (1,2,3-oxadiazolium-5-olate) and 1,3,4-thiadiazolium derivatives have been the most extensively studied, drawing particular attention to their pronounced antineoplastic activity against melanoma, hepatocellular carcinoma, breast cancer and glioblastoma models. Their anticancer effects are closely linked to mitochondrial bioenergetic disruption, including uncoupling of oxidative phosphorylation, inhibition of respiratory complexes, dissipation of the mitochondrial membrane potential, and stimulation of F1Fo-ATPase activity, which together cause ATP depletion, redox imbalance, and apoptosis induction. This review provides a comprehensive analysis of the structural features that govern these biological properties, the antitumor efficacy of sydnones and thiadiazolium derivatives across various cancer models, and the underlying mitochondrial mechanisms. By integrating chemical, pharmacological, and bioenergetic perspectives, this article highlights the potential of mesoionic compounds as versatile scaffolds for the anticancer drug development, emphasizing their preclinical antitumoral activities, the mechanisms related to cell bioenergetics, and the challenges to improve the bioviability through nanotechnologies.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149172329","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The impact of paroxetine on insulin secretion and sensitivity through AKT/GLUT4 axis.","authors":"Nidal A Qinna, Khaled Al-Khatib, Ghayda' AlDabet, Razan M AbdulHadi, Raghad H Mosleh, Bayan Alkhawaja, Bayan Y Ghanim","doi":"10.1007/s00210-026-05966-7","DOIUrl":"https://doi.org/10.1007/s00210-026-05966-7","url":null,"abstract":"<p><p>Selective serotonin reuptake inhibitors (SSRIs) are reported to be implicated in altering glucose homeostasis and inducing hypoglycemia in diabetic patients and mice. Herein, the effects of paroxetine on glucose homeostasis, insulin secretion, and insulin sensitivity were investigated in both healthy and streptozotocin-induced-insulin deficient mouse model. Mice were administered with paroxetine (1, 10, and 50 mg/kg) and fasting insulin levels and glucose-stimulated insulin secretion were assessed in healthy mice, whereas the glycemic profile in diabetic mice was evaluated after glucose or insulin challenge. Muscle mRNA expression of insulin signaling-relevant genes was analyzed, in addition to protein kinase B (PKB/Akt) activity and glucose transporter 4 (GLUT4) plasma membrane expression assessed in C2C12 myotubes. Paroxetine modulated glucose homeostasis and reduced the spike in blood glucose in diabetic mice in a dose-dependent manner after a glucose tolerance test. On the other hand, a reverse relationship was observed in the insulin tolerance test, with no evidence of acute hypoglycemia, suggesting that paroxetine did not further exacerbate insulin-induced glucose lowering under the tested conditions. Paroxetine (50 mg/kg) significantly increased fasting insulin secretion and upregulated genes involved in insulin receptor and Akt signaling, while reducing Glut4 mRNA expression. At 10 mg/kg, paroxetine significantly elevated Akt phosphorylation (p < 0.01). Paroxetine enhanced GLUT4 translocation and Akt phosphorylation in C2C12 myotubes. These findings suggest that paroxetine influences glucose homeostasis in diabetic conditions without causing acute hypoglycemia. Nevertheless, further preclinical and clinical investigations are warranted to clarify its metabolic effects and to determine the clinical implications for glycemic management in diabetic patients receiving paroxetine.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2026-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149137770","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}