Pharmacological Reports最新文献

{"title":"Correction: Marizomib in the therapy of brain tumors-how far did we go and where do we stand?","authors":"Magdalena Kusaczuk, Wiktoria Monika Piskorz, Julia Domasik","doi":"10.1007/s43440-025-00755-0","DOIUrl":"https://doi.org/10.1007/s43440-025-00755-0","url":null,"abstract":"","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144507502","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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 muscarinic and mGlu receptors modulators on MK-801-induced impairments in NO-dependent processes both in vitro and in vivo.","authors":"Grzegorz Burnat, Michał Santocki, Leszek Kalinowski, Joanna M Wierońska","doi":"10.1007/s43440-025-00752-3","DOIUrl":"https://doi.org/10.1007/s43440-025-00752-3","url":null,"abstract":"<p><strong>Background: </strong>Schizophrenia is a mental disorder with multifactorial etiology including positive, negative and cognitive symptoms. Nitric oxide (NO֗)-related biochemical pathways significantly contribute to the disease's pathophysiology and subsequent antipsychotic treatment. Recently, metabotropic glutamatergic (mGlu) or muscarinic (M) receptors have been considered as potent antipsychotics with the potential to reverse cognitive symptoms. The aim of this study was to investigate how selected mGlu or muscarinic receptor ligands regulate the most important aspects of NO֗-related neurotransmission.</p><p><strong>Methods: </strong>In this study, MK-801-the tool compound that induces schizophrenia-related changes-was used alone or with mGlu or muscarinic receptor ligands. Positive allosteric modulators (PAM) of mGlu₂ (LY487379), mGlu₅ (CDPPB), M₁ (VU0357017) and M₄ (VU0152100) receptors were administered. cGMP levels, superoxide dismutase (SOD) activity, nitrite and GLT-1 s-nitrosilation processes were investigated in mouse brain and plasma samples, while oxidative stress was measured in vitro with the use of mouse or human astrocytic cell lines.</p><p><strong>Results: </strong>MK-801 did not change cGMP levels, while a decrease was observed in mice treated with VU0357017 or LY487379 in parallel. Increased SOD activity was observed in the cortex of MK-801-treated mice, and the compounds, with the exception of CDPPB, prevented this effect. The investigated compounds also prevented an MK-801-induced increase in plasma nitrite levels. GLT-1 protein was decreased after MK-801 treatment which was not evident in mice administered with muscarinic or mGlu ligands. GLT-1 S-nitrosilation was increased in all groups. In vitro studies revealed the potency of these compounds in counteracting MK-801-induced oxidative stress.</p><p><strong>Conclusions: </strong>The present data confirm that both mGlu and muscarinic receptor ligands may exert antipsychotic effects through biochemical pathways regulated by NO֗, in particular by decreasing oxidative stress indicators.</p>","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144476285","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A novel 2-oxopyrrolidine derivative (LN-53) efficiently induces Nrf-2 signaling pathway activation in human epidermal keratinocytes.","authors":"Basak Ezgi Sarac, Laura Nissim, Dilara Karaguzel, Gokhan Arik, Shirin Kahremany, Edward E Korshin, Arie Gruzman, Cagatay Karaaslan","doi":"10.1007/s43440-025-00757-y","DOIUrl":"https://doi.org/10.1007/s43440-025-00757-y","url":null,"abstract":"<p><strong>Background: </strong>The skin is a pivotal organ that serves as a physical barrier, protecting the body from harmful substances such as pathogens, allergens, and other environmental irritants. Chronic inflammation in the skin, along with the anthropogenic effects, can cause reactive oxygen species (ROS) overproduction. Prolonged exposure to elevated ROS levels and inadequate antioxidant defenses in the skin can contribute to the onset of various skin disorders. The nuclear factor erythroid 2-related factor-2 (Nrf-2) signaling pathway plays a key role in enhancing antioxidant capacity by promoting the production of antioxidant and detoxifying molecules. Consequently, pharmacological activation of the Nrf-2 pathway may help restore the oxidant-antioxidant balance, thereby improving therapeutic outcomes for chronic skin disorders. This study aimed to investigate the potential effect of novel agent: (5-((4-(4-(methoxycarbonyl)-2-oxopyrrolidin-1-yl)phenyl)carbamoyl)benzene-1,2,3-triyl triacetate (LN-53), synthesized based on the structure of previously developed by our team lead compound SK-119, on Nrf-2 signaling pathway in human epidermal keratinocytes (HEKs) at mRNA and protein level.</p><p><strong>Methods: </strong>The cytotoxicity of LN-53 was evaluated by MTT, LDH, live/dead cell staining, and caspase-3,-8,-9 multiplex activity assays. Intracellular ROS production was assessed by DCFH-DA staining. The Nrf-2 gene was silenced by transient transfection using human Nrf-2 siRNA. Nrf-2 and related factors (heme oxygenase-1 (HO-1) and NAD(P)H dehydrogenase: quinone-1 (NQO1)) were evaluated at the mRNA level by qPCR and protein level in nuclear and cytosolic fractions by Nrf-2 activation assay and Western blot. The levels of inflammatory cytokines (IL-6 and IL-8) in supernatants were determined by ELISA.</p><p><strong>Results: </strong>Our results indicate that LN-53 effectively reduces intracellular ROS production triggered by tert-butyl hydroperoxide (TBHP), without leading to any noticeable cell damage. It promoted the nuclear translocation of Nrf-2 and induced the production of Nrf-2, HO-1, and NQO1 at both the mRNA and protein levels. LN-53-mediated alterations in antioxidant gene expressions were blocked by Nrf-2 knockdown. LN-53 treatment also suppressed the release of IL-6 and IL-8 cytokines mediated by TBHP exposure. Additionally, novel compound LN-53 was found to be more stable than the parent compound SK-119.</p><p><strong>Conclusion: </strong>LN-53 can effectively induce antioxidant mechanisms by promoting Nrf-2 nuclear translocation and suppressing ROS production in human epidermal keratinocytes. These data may suggest that LN-53 can contribute to maintaining redox balance and homeostasis in the skin.</p>","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144476284","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the pharmacological mechanisms and therapeutic implications of galangin against neurological disorders.","authors":"Xueying Zhang, Guangcheng Zhong, Haike Wu","doi":"10.1007/s43440-025-00756-z","DOIUrl":"10.1007/s43440-025-00756-z","url":null,"abstract":"<p><p>Neurological disorders represent a leading cause of mortality and disability worldwide, encompassing a broad spectrum of prevalent conditions such as Alzheimer's disease, epilepsy, and stroke. In recent years, natural compounds have garnered increasing attention as potential therapeutic and preventive agents for neurological disorders. Galangin, a naturally occurring flavonoid primarily derived from Alpinia officinarum Hance, exhibits diverse biological properties, including notable neuroprotective, anti-tumor, and anti-inflammatory effects. Emerging evidence indicates that galangin exerts significant neuroprotective effects through multiple mechanisms. This review systematically summarizes the in vivo metabolism and pharmacokinetics of galangin, elucidates its mechanism of action, and highlights recent advances in its application for neurological disorders. Furthermore, the prospect of nanodrug carriers for enhancing the therapeutic efficacy of galangin is explored. Additionally, this review addresses the current research limitations and outlines future research directions to provide a theoretical foundation for its clinical application in neurological disorders. Collectively, the findings underscore the extensive pharmacological properties and therapeutic potential of galangin, highlighting its promise as a novel candidate for the treatment and prevention of neurological disorders and warranting further in-depth investigation and development.</p>","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144333670","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The application of telmisartan in central nervous system disorders.","authors":"Wei Quan, Shui-Xian Zhang, Xu-Yang Zhang, Xi Chen, Chao Yang, Zhi-Yu Li, Rong Hu","doi":"10.1007/s43440-025-00737-2","DOIUrl":"https://doi.org/10.1007/s43440-025-00737-2","url":null,"abstract":"<p><p>Telmisartan, a well-established antihypertensive drug, has shown promising therapeutic potential for a variety of central nervous system (CNS) disorders. This review outlines the fundamental characteristics of telmisartan, focusing on its dual pharmacological effects as an angiotensin II type 1 receptor (AT1R) antagonist and a peroxisome proliferator-activated receptor (PPAR) γ activator. These mechanisms underpin its neuroprotective and anti-inflammatory effects, which are essential to its therapeutic benefits in CNS diseases. Telmisartan modulates key cellular components of the CNS, including microglia, astrocytes, oligodendrocytes, vascular endothelial cells, and neurons, thereby offering protection against neuroinflammation, oxidative stress, and neuronal damage. We summarize telmisartan's efficacy in addressing a range of neurological conditions, such as stroke, traumatic brain injury, dementia, Parkinson's disease, demyelinating diseases, psychiatric disorders, and gliomas. By targeting multiple pathways involved in these disorders, telmisartan demonstrates potential as both an adjunctive and standalone therapy. Its ability to attenuate neuroinflammation and promote cellular repair highlights its versatility in CNS disease management. This review underscores the potential of telmisartan as a valuable therapeutic option for CNS disorders, warranting continued exploration to optimize its clinical application.</p>","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144326538","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of curcumin on vascular smooth muscle cells: implications for health and disease.","authors":"Majid Shohrati, Farshad Abedi, Mahdi Bagheri, Amirhossein Sahebkar","doi":"10.1007/s43440-025-00744-3","DOIUrl":"https://doi.org/10.1007/s43440-025-00744-3","url":null,"abstract":"<p><p>Vascular smooth muscle cells (SMCs) are pivotal in regulating vascular tone and integrity. Their dysregulation significantly contributes to the pathophysiology of cardiovascular ailments, including atherosclerosis, blood pressure, and vascular remodeling. Curcumin, a polyphenol with a natural origin in turmeric, exhibits promising therapeutic properties due to its remarkable anti-inflammatory, antioxidant, and antiproliferative characteristics. This review aims to assess the effects of curcumin on vascular SMC behavior, encompassing its impact on proliferation, migration, phenotypic switching, and extracellular matrix remodeling. The underlying molecular mechanisms are highlighted, particularly curcumin's modulation of signaling pathways such as nuclear factor-kappa B (NF-κB), mitogen-activated protein kinase (MAPK), and nuclear transcription factor E2-related factor-2 (Nrf2) signaling pathways, as well as its ability to decrease oxidative stress and inflammatory cytokine generation. Furthermore, we evaluate the implications of the results for vascular health and disease, emphasizing curcumin's potential to prevent or mitigate atherosclerosis, restenosis, and hypertension. Despite promising preclinical evidence, challenges related to curcumin's bioavailability and clinical translation remain.</p>","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144226187","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chalcone-9: a novel inhibitor of the JAK-STAT pathway with potent anti-cancer effects in triple-negative breast cancer cells.","authors":"Song-Hee Lee, Haeri Lee, Yong-Jin Kwon, Seul-Ki Kim, Eun-Bi Seo, Jie Ohn Sohn, Byung-Hak Kim, Jung-Youl Park, Sang-Kyu Ye","doi":"10.1007/s43440-025-00721-w","DOIUrl":"10.1007/s43440-025-00721-w","url":null,"abstract":"<p><strong>Background: </strong>Breast cancer remains the leading cause of cancer incidence and mortality among women worldwide, with triple-negative breast cancer (TNBC) posing significant treatment challenges. The dysregulation of the Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway contributes to tumor progression, making it a potential therapeutic target. Chalcones, known for their diverse biological activities, including anti-cancer effects, hold promise for drug development. This study explores the anti-cancer activity of (E)-4-(3-(2-(benzyloxy)-6-hydroxyphenyl)-3-oxoprop-1-en-1-yl)benzoic acid (chalcone-9), a novel chalcone derivative.</p><p><strong>Methods: </strong>The cytotoxic effects of chalcone-9 were evaluated in breast cancer cell lines, including TNBC lines MDA-MB-231 and MDA-MB-468. Western blotting and qRT-PCR were used to analyze the impact on JAK1, JAK2, STAT1, and STAT3 activation and their downstream gene expression. In silico molecular docking analysis was conducted to determine whether chalcone-9 can interact with JAK1 and JAK2. A wound healing assay was used to observe the effect of chalcone-9 on tumor cell migration, and flow cytometry was employed to analyze whether chalcone-9 inhibits tumor cell cycle progression and induces apoptosis. The expression of apoptosis markers was also assessed.</p><p><strong>Results: </strong>Chalcone-9 exhibited dose-dependent cytotoxicity in breast cancer cell lines, with TNBC cells showing higher sensitivity. Chalcone-9 effectively inhibited the activation of JAK1, JAK2, STAT1, and STAT3, outperforming conventional JAK/STAT inhibitors. The structure of chalcone-9 was confirmed to stably interact with JAK1 and JAK2 proteins. It also suppressed STAT1 and STAT3 target gene expression, reduced tumor cell migration, and induced apoptosis, as evidenced by PARP and caspase cleavage and decreased survivin levels.</p><p><strong>Conclusions: </strong>Chalcone-9 demonstrates significant anti-cancer activity, particularly against TNBC. By targeting the JAK/STAT pathway and promoting apoptosis, chalcone-9 emerges as a promising therapeutic candidate for aggressive breast cancers.</p>","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":" ","pages":"761-774"},"PeriodicalIF":3.6,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12066378/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143812120","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of magnolol on the liver antioxidant status in rats with diabetes.","authors":"Sławomir Dudek, Weronika Borymska, Maria Zych, Dżesika Chełminiak, Magdalena Kimsa-Dudek, Ilona Kaczmarczyk-Żebrowska","doi":"10.1007/s43440-025-00718-5","DOIUrl":"10.1007/s43440-025-00718-5","url":null,"abstract":"<p><strong>Background: </strong>Magnolol isolated from Magnolia (Magnolia sp.) flowers are used to support the treatment of diabetes. The aim of this study was to investigate the effects of magnolol on the liver antioxidant status in rats with type 2 diabetes and assess oxidative stress parameters at both biochemical and molecular levels.</p><p><strong>Methods: </strong>Mature male Wistar rats with high-fat diet (HFD) and streptozotocin (STZ)-induced type 2 diabetes were administered magnolol at doses of 5 or 25 mg/kg body weight po for 4 weeks. Then, the activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx), the concentrations of advanced protein oxidation products (AOPPs) and malondialdehyde (MDA), the total antioxidant response (TAR), and the total oxidative status (TOS) were assessed using commercially available colorimetric kits according to the manufacturers' protocols. The mRNA levels of the cytochrome P450 family 1 subfamily A member 2 (CYP1A2), cytochrome P450 family 2 subfamily E member 1 (CYP2E1), nuclear factor erythroid 2-related factor 2 (NFE2L2), and Kelch like ECH-associated protein 1 (KEAP1) genes were determined using real-time quantitative reverse transcription-polymerase chain reaction (RT‒qPCR). All parameters were analyzed in liver samples.</p><p><strong>Results: </strong>Compared with 5 mg/kg magnolol, 25 mg/kg magnolol had a more beneficial effect on several indicators of oxidative stress in the liver observed as significant decreases in the activity of SOD and CAT, as well as decreased MDA concentrations. Further, significant increases in the concentrations of AOPPs and native thiols were observed. The gene encoding CYP2E1 was upregulated in diabetic rats compared with control rats. Moreover, compared with diabetic rats, diabetic rats treated with 25 mg/kg magnolol presented increased expression of the KEAP1 gene.</p><p><strong>Conclusions: </strong>The induction of diabetes is known to disturb redox homeostasis. The administration of magnolol at the higher dose used in this study, might counteract the changes in the liver antioxidant status at both the molecular and biochemical levels. Owing to the positive alterations in some oxidative stress parameters, after further in-depth study, magnolol may be considered a promising compound that could be used to complement diabetes treatment.</p>","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":" ","pages":"716-728"},"PeriodicalIF":3.6,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143701026","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"High BMI predicts poor cancer pain relief when rotating from oral opioids to transdermal Fentanyl: a two-center retrospective study.","authors":"Ya Chen, Songling Han, Xiaogang Hu, Xue Ma, Yue Qiu, Yuelu Tang, Xiaoxiao Wang, Lixian Li, Chao Li, Wanyi Chen","doi":"10.1007/s43440-025-00723-8","DOIUrl":"10.1007/s43440-025-00723-8","url":null,"abstract":"<p><strong>Background: </strong>The analgesic effect of transdermal fentanyl (TDF) differs among cancer pain patients. This study aims to investigate the relationship between clinical factors and pain relief when using TDF in cancer pain patients who rotate from oral opioids to TDF.</p><p><strong>Methods: </strong>A two-center retrospective study was conducted in Chongqing University Cancer Hospital and Sichuan Cancer Hospital, including adult cancer pain patients who rotated from oral opioids to TDF between 2018 and 2022. Based on the clinical characteristics, logistic regressions and directed acyclic graphs (DAG) were employed to identify significant factors influencing the efficacy of TDF. The study adhered to STROBE guidelines.</p><p><strong>Results: </strong>This survey included 359 patients, among them, 254 patients (70.8%) attained good pain relief after rotating to TDF. 59.3% of patients utilized TDF at standard dosage, while 24.8% used underdose TDF, with only 52.8% achieving adequate pain relief, significantly lower than other groups (p < 0.001). Initial univariable analysis of 22 clinical factors among the standard dose group showed that a higher body mass index (BMI, median 23.2 kg/m² vs. 21.0 kg/m², OR = 0.83 [0.75-0.91], p < 0.001) and the presence of lung cancer (OR = 0.31 [0.11-0.89], p = 0.030) predicted potentially unsatisfactory pain control after TDF treatment. Subsequently, a multivariable regression analysis based on DAG-directed factor selection identified BMI (OR = 0.82 [0.74-0.92], adjusted p < 0.01) as the only independent factor influencing TDF effectiveness.</p><p><strong>Conclusions: </strong>Our study suggested that high BMI was a significant predictor of poor cancer pain relief when rotating from oral opioids to TDF, and provides a useful measurement of managing adult cancer pain when using TDF.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov, NCT06369961, registered on April 11, 2024; https://clinicaltrials.gov/study/NCT06369961 .</p>","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":"77 3","pages":"789-799"},"PeriodicalIF":3.6,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144017164","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetic liability for anxiety and treatment response to the monoamine stabilizer OSU6162 in alcohol dependence: a retrospective secondary analysis.","authors":"Mun-Gwan Hong, Lotfi Khemiri, Joar Guterstam, Johan Franck, Nitya Jayaram-Lindström, Philippe A Melas","doi":"10.1007/s43440-025-00707-8","DOIUrl":"10.1007/s43440-025-00707-8","url":null,"abstract":"<p><strong>Background: </strong>OSU6162, a monoamine stabilizer, has demonstrated efficacy in reducing alcohol and anxiety-related behaviors in preclinical settings. In a previous randomized, double-blind, placebo-controlled trial involving patients with alcohol dependence (AD), OSU6162 significantly reduced craving for alcohol but did not alter drinking behaviors. This retrospective secondary analysis explores whether genetic predispositions related to AD and associated traits might influence the response to OSU6162 treatment in original trial participants.</p><p><strong>Methods: </strong>Polygenic risk scores (PRSs) were calculated for 48 AD patients using PRSice-2 and genome-wide association study (GWAS) data for (i) alcohol use disorder and alcohol consumption, (ii) problematic alcohol use, (iii) drinks per week, (iv) major depression, and (v) anxiety (case-control comparisons and quantitative anxiety factor scores). Linear regression analyses, adjusted for population stratification, assessed interaction effects between PRSs and treatment type (OSU6162 or placebo) on various clinical outcomes.</p><p><strong>Results: </strong>Significant interactions were found between treatment type and anxiety factor score PRS at the genome-wide significance threshold. In the OSU6162-treated group, a higher anxiety PRS was associated with reductions in the number of drinks consumed (FDR = 0.0017), percentage of heavy drinking days (FDR = 0.0060), and percentage of drinking days (FDR = 0.0017), with a trend toward reduced blood phosphatidylethanol (PEth) levels (FDR = 0.068). These associations were absent in the placebo group.</p><p><strong>Conclusions: </strong>These preliminary findings suggest that anxiety PRS may help predict response to OSU6162 treatment in AD. Further research with larger cohorts and more comprehensive genetic data is needed to confirm these results and advance personalized medicine approaches for alcohol use disorder.</p>","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":" ","pages":"840-849"},"PeriodicalIF":3.6,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12066376/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143605912","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}