Fundamental & Clinical Pharmacology最新文献

{"title":"Dual Targeting of Akt and MAPK Pathways With Capivasertib and B-Raf Inhibitors Synergistically Suppresses Tumor Growth in B-Raf-Mutated Melanoma Models.","authors":"Jun Tang, Lingling Zhao, Yuanyuan Zhu, Baoxue Duan","doi":"10.1111/fcp.70088","DOIUrl":"https://doi.org/10.1111/fcp.70088","url":null,"abstract":"<p><p>Resistance to B-Raf inhibitors in melanoma poses a significant challenge to effective treatment. This study investigates the synergistic effects of capivasertib, an Akt pathway inhibitor, in combination with B-Raf inhibitors (vemurafenib and encorafenib) in B-Raf-mutated melanoma models. Combination index analysis demonstrated strong synergy between capivasertib and B-Raf inhibitors in melanoma cells. In contrast, combinations of capivasertib with standard chemotherapeutics were antagonistic, underscoring the specificity of the interaction. Mechanistic studies revealed that capivasertib effectively suppressed Akt signaling. Synergism was abolished in Akt-overexpressing cells, confirming Akt's role in the observed combination effects. The combination treatments significantly reduced tumor growth, with tumor volumes in the capivasertib-vemurafenib and capivasertib-encorafenib groups reduced by ~70% relative to control. Notably, this inhibition was sustained for at least 8 weeks, with tumors in the combination groups remaining minimal, while those in the control group reached maximal size by Week 4. Systemic toxicity analyses revealed no significant changes in body weight or serum markers of pancreatic, kidney, or liver function. These findings establish capivasertib and B-Raf inhibitor combinations as a safe and effective strategy for overcoming resistance B-Raf-mutated melanoma, providing new insights into the potential of dual pathway targeting.</p>","PeriodicalId":12657,"journal":{"name":"Fundamental & Clinical Pharmacology","volume":"40 3","pages":"e70088"},"PeriodicalIF":2.5,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147769442","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":"Repurposing Cimetidine as a Therapeutic Candidate for Irritable Bowel Syndrome in a Rat Model.","authors":"Tsukasa Nozu, Saori Miyagishi, Masatomo Ishioh, Kaoru Takakusaki, Toshikatsu Okumura","doi":"10.1111/fcp.70091","DOIUrl":"https://doi.org/10.1111/fcp.70091","url":null,"abstract":"<p><strong>Background: </strong>Visceral hypersensitivity and impaired intestinal barrier function are hallmark features of irritable bowel syndrome (IBS), linked to activation of corticotropin-releasing factor (CRF), Toll-like receptor 4 (TLR4), and proinflammatory cytokine pathways. Cimetidine, a classical H₂ blocker, has been shown to inhibit Na⁺/H⁺ exchangers (NHEs), thereby potentially suppressing proinflammatory cytokine release.</p><p><strong>Objectives: </strong>This study examined whether cimetidine alleviates visceral hypersensitivity and colonic hyperpermeability in rat models of IBS.</p><p><strong>Methods: </strong>Visceral pain threshold in response to colonic balloon distention was assessed by electromyographic detection of abdominal muscle contractions during colonic balloon distention, and colonic permeability was measured using Evans blue uptake in LPS- and CRF-induced IBS models in male Sprague-Dawley rats.</p><p><strong>Results: </strong>Intragastric cimetidine (20-100 mg/kg daily for 3 days) prevented LPS-induced visceral hypersensitivity and colonic hyperpermeability dose-dependently and also attenuated CRF-induced changes. In contrast, famotidine, another H₂ blocker, did not replicate these effects. Amiloride, an NHE inhibitor, mimicked cimetidine's effects, both of which were abolished by intracisternal SB-334867, an orexin 1 receptor antagonist. Furthermore, atropine, sulpiride, and N^G-nitro-L-arginine methyl ester, a nitric oxide (NO) synthesis inhibitor, but not scopolamine butylbromide, a peripheral muscarinic receptor antagonist, or domperidone, a peripheral dopamine D₂ receptor antagonist, blocked cimetidine's action.</p><p><strong>Conclusion: </strong>These findings suggest that cimetidine prevents visceral hypersensitivity and colonic hyperpermeability in IBS models through mechanisms involving central orexin signaling possibly triggered by NHE inhibition, NO, and central muscarinic and dopamine D₂ receptor pathways. These findings may provide a basis for future therapeutic approaches targeting IBS.</p>","PeriodicalId":12657,"journal":{"name":"Fundamental & Clinical Pharmacology","volume":"40 3","pages":"e70091"},"PeriodicalIF":2.5,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147837009","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":"Dexamethasone-Mediated Regulation of CYP3A4 and UGTs in Human Hepatoma HuH-7 Cells.","authors":"Hana Yu, Song Hee Lee, Ji Hyeon Kim, Seung Jin Kim, Hee Eun Kang","doi":"10.1111/fcp.70089","DOIUrl":"https://doi.org/10.1111/fcp.70089","url":null,"abstract":"<p><strong>Background: </strong>The application of human hepatic cell lines to early drug discovery and development instead of human primary hepatocytes (HPHs) has been limited because of the low level of drug-metabolizing enzymes (DMEs).</p><p><strong>Objective: </strong>The study aimed to evaluate the effects of dexamethasone (DEX) treatment on DME expression, activities, and regulation in HuH-7 hepatoma cells.</p><p><strong>Methods: </strong>Expression and transcriptional regulation of major CYPs and UGTs in HuH-7 cells was evaluated by immunoblotting, probe substrate assays, and treatments with nuclear receptor agonists, including DEX, and antagonists.</p><p><strong>Results: </strong>DEX increased the expression and activity of cytochrome P450 (CYP) 3A4, uridine 5'-diphospho-glucuronosyltransferase (UGT) 1A1, and UGT2B7 but had minimal effects on CYP1A2, CYP2B6, or CYP2C9. These augmented activities of CYP3A4, UGT1A1, and UGT2B7 were concentration-dependently inhibited by their corresponding selective inhibitors. DEX-induced upregulation of CYP3A4 protein expression was abolished by co-treatment with the glucocorticoid receptor (GR) inhibitor, but not by co-treatment with the pregnane X receptor (PXR) inhibitor. However, treatment with PXR or constitutive androstane receptor (CAR) agonist did not lead to transcriptional activation of CYP3A4 and 2B6. Only CYP1A1 was transactivated by an aryl hydrocarbon receptor (AhR) ligand.</p><p><strong>Conclusion: </strong>Our results suggest that the activities of some major DMEs (CYP3A4, UGT1A1, and UGT2B7) in HuH-7 cells are promoted by DEX treatment possibly through GR activation. However, unlike HPHs, HuH-7 cells fail to show transcriptional regulation of DMEs by PXR or CAR, which limits their suitability for evaluating DME induction potential of investigational drugs.</p>","PeriodicalId":12657,"journal":{"name":"Fundamental & Clinical Pharmacology","volume":"40 3","pages":"e70089"},"PeriodicalIF":2.5,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13099280/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147769422","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Alogliptin Delays the Healing of Traumatic Oral Ulcers in the Buccal Mucosa of Wistar Rats.","authors":"Maria Imaculada de Queiroz Rodrigues, Joyce Ohana de Lima Martins, Debora de Souza Collares Maia Castelo-Branco, Paulo Goberlânio de Barros Silva, Fabrício Bitu Sousa, Mário Rogério Lima Mota, Ana Paula Negreiros Nunes Alves","doi":"10.1111/fcp.70090","DOIUrl":"https://doi.org/10.1111/fcp.70090","url":null,"abstract":"<p><strong>Objective: </strong>The objective of this study is to evaluate the influence of alogliptin treatment on the healing process of traumatic oral ulcers.</p><p><strong>Methods: </strong>Four experimental groups were used: control group (GC) and three test groups treated with oral Alogliptin at 1 (GTA1), 3 (GTA3), and 9 mg/kg/day (GTA9). Ulcer diameter, body weight, glycemic index, colony-forming unit (CFU), and discomfort were analyzed. Histological slides were prepared for healing scores, inflammatory cell counts, collagen deposition analysis, and immunohistochemistry.</p><p><strong>Results: </strong>Alogliptin treatment increased ulcer area (GTA3-7D: 5.2 ± 1.2; GTA9-3D: 11.8 ± 0.8; GTA9-7D: 5.8 ± 1.3; p < 0.001), CFU counts (p = 0.049), and Grimace/discomfort scores (p = 0.02), while reducing body weight gain (p = 0.007) in GTA3 and GTA9 groups. Microscopic analysis revealed higher histopathological scores (p = 0.039), increased mononuclear cells (p = 0.006), reduced polymorphonuclear cells (p < 0.05), and decreased collagen deposition (18.2 ± 2.6; p = 0.031) in GTA9. Lower TLR4 (p = 0.001) and TGF-β (p < 0.001) expression, alongside increased CD31 immunostaining (p < 0.001), were observed in GTA3 and GTA9, as well as reduced TLR2 expression (p = 0.001) in GTA9.</p><p><strong>Conclusion: </strong>Alogliptin delays oral ulcer healing by sustaining inflammation, reducing TGF-β expression, and impairing collagen deposition, and may contribute via reduced TLR2/TLR4 expression, increased microbial burden, and decreased TGF-β.</p>","PeriodicalId":12657,"journal":{"name":"Fundamental & Clinical Pharmacology","volume":"40 3","pages":"e70090"},"PeriodicalIF":2.5,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13105823/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147769366","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of a Single Oral Dose of Dexamphetamine or Zolpidem on Attention and Reaction Time in Healthy Men.","authors":"Veronika Pfoser-Poschacher, Michael Wolf, Michaela Bayerle-Eder, Teresa Wimmer, Daniela Boryshchuk, Christopher Gerner, Michael Wolzt","doi":"10.1111/fcp.70092","DOIUrl":"https://doi.org/10.1111/fcp.70092","url":null,"abstract":"<p><p>Psychotropic medicines are known to impair cognitive function acutely, but the specific effects of individual substances remain underexplored. This study investigates the effects of dexamphetamine and zolpidem on cognitive performance to quantify the potential risk of intake and their pharmacokinetic and pharmacodynamic relationship. This randomized, double-blind, placebo-controlled trial (EudraCT 2021-005381 - 17) included 60 healthy men aged 26 ± 5 (mean ± SD) years. Participants received a single oral dose of 30-mg dexamphetamine, 5-mg zolpidem, or placebo (n = 20 per group). Cognitive performance was assessed at baseline and 3 and 8 h after dosing using the computerized Psytest system. Dexamphetamine and zolpidem improved sustained attention, with significant reduction of omissions at 8 h. Reaction time improved in both groups, but zolpidem impaired phasic alertness. Working memory remained unchanged. Plasma concentration of dexamphetamine and zolpidem was 70.8 ± 10.4 ng/mL and 39.0 ± 20.7 ng/mL at 3 h and 45.9 ± 7.9 ng/mL and 8.7 ± 6.6 ng/mL at 8 h, respectively. No correlation between drug plasma concentration and cognitive performance measures was demonstrable. Dexamphetamine caused the strongest subjective effects and highest liking ratings, whereas zolpidem elicited greater subjective dislike. Tolerability was best with placebo, followed by zolpidem and dexamphetamine. Single therapeutic doses of dexamphetamine and zolpidem modestly affected cognitive function 3 h after intake, with no relationship between cognitive performance and the study medicines' plasma concentration. Both medicines improve cognition after 8 h but differed in subjective emotional effects. Nevertheless, generalizability is limited by the inclusion of healthy men only. Trial Registration: EudraCT: Nr: 2021-005381-17.</p>","PeriodicalId":12657,"journal":{"name":"Fundamental & Clinical Pharmacology","volume":"40 3","pages":"e70092"},"PeriodicalIF":2.5,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13144445/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147836951","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Preventive Effects of trans-4-Methoxy-β-nitrostyrene on Monocrotaline-Induced Pulmonary Arterial Hypertension in Rats","authors":"Matyelle Jussára Rodrigues-Silva,&nbsp;Rodrigo José Bezerra de Siqueira,&nbsp;Karoline Gonzaga-Costa,&nbsp;Yeimer Antonio Santiago Guevara,&nbsp;Marcus Lins Queiroga,&nbsp;Davi Benevides Almeida,&nbsp;Alexandre Havt,&nbsp;Renata Fereirra Carvalho Leitão,&nbsp;Liova Chabot Díaz,&nbsp;Ana Paula Negreiros Nunes Alves,&nbsp;Glória Pinto Duarte,&nbsp;Rosivaldo Santos Borges,&nbsp;Armênio Aguiar dos Santos,&nbsp;Pedro Jorge Caldas Magalhães,&nbsp;Saad Lahlou","doi":"10.1111/fcp.70078","DOIUrl":"10.1111/fcp.70078","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The soluble guanylate cyclase (sGC)/GMPc pathway plays an important in pulmonary arterial hypertension (PAH).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>We investigated whether <i>trans</i>-4-methoxy-β-nitrostyrene (T4MN), a novel sGC stimulator, prevents development of monocrotaline (MCT)-induced HAP in rats.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>At Day 0 (D0), rats were injected with MCT (60 mg/kg, sc). Control (CNT) rats received an equal volume of MCT vehicle only. MCT-injected rats were divided into four groups, which were treated orally once a day from D1 to D28 with one of the following: T4MN vehicle (MCT-V group), T4MN at 18.75 mg/kg (MCT-T4MN1 group), T4MN at 37.50 mg/kg (MCT-T4MN2 group), or sildenafil (SIL; 10 mg/kg) (MCT-SIL group).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Compared to the CNT group, MCT treatment induced a significant increase in heart weight to body weight, lung weight to body weight, and right ventricular systolic pressure but significantly reduced the maximum vasorelaxation (Rmax) induced by acetylcholine in aortic ring preparations. Indeed, MCT treatment increased the wall thickness of small pulmonary arterioles and reduced the mRNA levels of BMPR2, eNOS, and VEGF-A while it increased that of IL-6 in pulmonary tissue. All these effects of MCT, except those on mRNA expression levels in the lungs, were significantly reduced by preventive treatment with T4MN or SIL.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Taken together, the present study provided the first evidence that T4MN prevents the development of MCT-induced HAP in rats. Further mechanistic studies of these protective effects of T4MN are warranted.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12657,"journal":{"name":"Fundamental & Clinical Pharmacology","volume":"40 3","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147511526","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":"Factors Associated With Cocaine Use Disorder: Results From the French Nationwide Repeated Cross-Sectional OPPIDUM Study (2019–2023)","authors":"Zenab Alhamidi,&nbsp;Clémence Lacroix,&nbsp;Elisabeth Jouve,&nbsp;Thomas Soeiro,&nbsp;Céline Eiden,&nbsp;Joëlle Micallef","doi":"10.1111/fcp.70081","DOIUrl":"10.1111/fcp.70081","url":null,"abstract":"<p>Cocaine use has increased both globally and nationally. This trend is accompanied by a rise in clinical complications. The objective of our study was to identify factors observed to be associated with cocaine use disorder, using data from the OPPIDUM program, collecting information directly from patients with substance use disorders recruiting in care or harm reduction facilities. Cocaine users were divided into two groups: cocaine use disorder and simple use. A univariate analysis was performed to compare the groups, followed by a multivariate analysis to identify factors associated with cocaine use disorder. Between 2019 and 2023, 6863 cocaine users (28% of all OPPIDUM participants) from 116 addiction treatment centers were included. Several factors were found to be significantly associated with cocaine use disorder: extreme precariousness (OR = 1.34, 95% CI [1.12–1.61], <i>p</i> = 0.002), cocaine-only use (OR = 1.90, 95% CI [1.45–2.50], <i>p</i> &lt; 0.0001), alcohol dependence (OR = 1.48, 95% CI [1.30–1.68], p &lt; 0.0001), and use of antidepressants and antipsychotics (OR = 2.08, 95% CI [1.37–3.16], <i>p</i> = 0.001; OR = 1.94, 95% CI [1.40–2.69], <i>p</i> &lt; 0.001). These findings highlight several key factors associated with cocaine use disorder and their clinical implications. The study has limitations: potential selection bias, repeated inclusion of the same users across years, multiple modes of cocaine use, and the exploratory nature of the analyses due to uncontrolled alpha risk. Nevertheless, these insights can help healthcare professionals better understand patient profiles and provide more tailored care and prevention strategies.</p>","PeriodicalId":12657,"journal":{"name":"Fundamental & Clinical Pharmacology","volume":"40 3","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13019272/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147511558","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting Neuroinflammation in Alzheimer's Disease: Repurposed Nucleoside Reverse Transcriptase Inhibitors and the Therapeutic Potential of Kamuvudine-9","authors":"Mariyam Hussain,&nbsp;Mohammad Ikram,&nbsp;Divya Vohora","doi":"10.1111/fcp.70079","DOIUrl":"10.1111/fcp.70079","url":null,"abstract":"<div>\u0000 \u0000 <p>Alzheimer's disease (AD) is a progressive neurological illness that causes cognitive deterioration. Current medications only help with the symptoms to a limited extent. Over the past decade, nucleoside reverse transcriptase inhibitors (NRTIs), historically used as antiretrovirals, have appeared as surprising contenders for modifying <span>AD</span>. Aside from their antiviral activity, NRTIs have immunomodulatory actions, such as inhibiting the NLRP3 inflammasome, lowering amyloid and tau pathology and modulating neuroinflammation. A second-generation analogue, Kamuvudine-9, has been designed to balance these neuroprotective advantages with reduced mitochondrial toxicity and off-target antiviral effects, offering a safer long-term solution for chronic neurodegenerative disorders. This review synthesises mechanistic data, preclinical data, observational studies and new clinical findings to make a unified case for NRTIs and K-9 as multitarget therapeutic compounds in <span>AD</span>. By emphasising their dual mechanism, retroelement inhibition and inflammasome blockade coupled with innovation in drug delivery and pharmacogenomics, we highlight how repurposing this class would remake the therapeutic landscape. In contrast to amyloid-directed interventions, NRTIs and K-9 act on converging inflammatory and genetic mechanisms that mediate both amyloid and tau pathology, making them universal modulators of disease course. Prospects for future advances in precision medicine, nanocarrier delivery and large-scale validation of interventions may reveal a new generation of accessible, disease-modifying treatments for <span>AD</span>.</p>\u0000 </div>","PeriodicalId":12657,"journal":{"name":"Fundamental & Clinical Pharmacology","volume":"40 3","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147511602","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: Vitamin D3 Potentiates the Nephroprotective Effects of Vildagliptin–Metformin Combination in a Rat Model of Metabolic Syndrome","authors":"","doi":"10.1111/fcp.70080","DOIUrl":"10.1111/fcp.70080","url":null,"abstract":"<p>\u0000 <b>RETRACTION</b>: <span>N. S. Wahba</span>, <span>R. H. Abdel-Ghany</span>, <span>S. A. Ghareib</span>, <span>M. Abdel-Aal</span>, <span>A. E. Alsemeh</span>, and <span>D. Sabry</span>, “ <span>Vitamin D3 Potentiates the Nephroprotective Effects of Vildagliptin–Metformin Combination in a Rat Model of Metabolic Syndrome</span>,” <i>Fundamental &amp; Clinical Pharmacology</i> <span>36</span>, no. <span>2</span> (<span>2022</span>): <span>306</span>–<span>323</span>, https://doi.org/10.1111/fcp.12721.\u0000 </p><p>The above article, published online on 28 August 2021 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the journal Editor-in-Chief, Luc Zimmer; the Société Française de Pharmacologie et de Thérapeutique; and John Wiley &amp; Sons Ltd. The retraction has been agreed upon following concerns raised by a third-party regarding data overlaps between this article and two other articles published elsewhere by the same authors. Following investigation, the editors confirmed that there are substantial overlaps between the three papers. The authors provided numerical data but were unable to provide any raw data due to the time that has elapsed since publication. They explained that the three studies were closely related, and that the two overlapping articles were cited in their paper. However, this explanation does not account for the overlaps of data between different treatments and groups across the three articles. Given the extent of the issues identified, the editors have lost confidence in the data presented and consider the conclusions unreliable. The authors disagree with the retraction.</p>","PeriodicalId":12657,"journal":{"name":"Fundamental & Clinical Pharmacology","volume":"40 2","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/fcp.70080","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147511532","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Non-Pulmonary Mechanisms of Action of Ambroxol in In Vivo Experimental Models: a Systematic Review","authors":"Michelline Joana Tenório Albuquerque Madruga Mesquita,&nbsp;Anne Caroline Silva Nogueira da Cruz,&nbsp;Rafael de Abreu Lima,&nbsp;Joana Tenório-Meireles,&nbsp;Arney José Nogueira Farias,&nbsp;Isabela Nogueira Santos,&nbsp;Gustavo Frota,&nbsp;Taciana Gabrielle Pinheiro de Moura Carvalho,&nbsp;Rafael Antônio Freire Carvalho,&nbsp;Jorge Antônio Meireles-Teixeira,&nbsp;Tereza Prazeres,&nbsp;Rafael Cardoso Carvalho,&nbsp;Maria do Socorro de Sousa Cartágenes,&nbsp;João Batista Santos Garcia","doi":"10.1111/fcp.70077","DOIUrl":"10.1111/fcp.70077","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Repositioning offers a cost-effective approach to discovering new therapeutic applications for existing medications. Ambroxol, primarily used as a mucolytic for respiratory diseases, has demonstrated anti-inflammatory, analgesic, and antioxidant properties, suggesting potential benefits in non-pulmonary conditions. This study conducted a systematic review to evaluate the efficacy of ambroxol in experimental disease models unrelated to the respiratory system.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Following registration in the Open Science Framework and adherence to the PICO strategy for formulating the guiding question, searches were performed in PUBMED/MEDLINE, EMBASE, and SCOPUS using the keywords: (Ambroxol) AND (Anti-Inflammatory Agents OR Analgesics OR Antioxidants) AND (Animals OR in vivo). The SYRCLE tool assessed methodological quality. Among 353 identified records, eight articles met eligibility criteria.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>These studies investigated ambroxol's effects in models of gastric lesions, neuropathic pain, psoriasis-like skin inflammation, hemorrhagic cystitis, and ischemia/reperfusion injuries in the liver and kidneys. Ambroxol doses ranged from 5 to 1000 mg/kg, predominantly administered orally. Its antioxidant properties were demonstrated by reducing free radicals and increasing enzymatic activity (SOD, CAT, GSH). Anti-inflammatory effects included a decrease in pro-inflammatory cytokines (TNF-α, IL-1β) and histological improvements. Antinociceptive action was observed through inhibition of voltage-gated sodium channels and reduction of oxidative stress, alleviating neuropathic pain.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Despite ambroxol's widespread clinical use, limited research has explored its non-respiratory applications. Existing studies suggest its promising therapeutic potential, reinforcing the need for further investigation into its role as an alternative treatment for various inflammatory and oxidative stress–related conditions beyond pulmonary diseases.</p>\u0000 </section>\u0000 </div>","PeriodicalId":12657,"journal":{"name":"Fundamental & Clinical Pharmacology","volume":"40 2","pages":""},"PeriodicalIF":2.5,"publicationDate":"2026-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12987714/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147456466","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}