Pharmacological Reports最新文献

筛选
英文 中文
High BMI predicts poor cancer pain relief when rotating from oral opioids to transdermal Fentanyl: a two-center retrospective study. 当从口服阿片类药物转向透皮芬太尼时,高BMI预示着癌症疼痛缓解不良:一项双中心回顾性研究。
IF 3.6 3区 医学
Pharmacological Reports Pub Date : 2025-06-01 Epub Date: 2025-04-11 DOI: 10.1007/s43440-025-00723-8
Ya Chen, Songling Han, Xiaogang Hu, Xue Ma, Yue Qiu, Yuelu Tang, Xiaoxiao Wang, Lixian Li, Chao Li, Wanyi Chen
{"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}
引用次数: 0
Genetic liability for anxiety and treatment response to the monoamine stabilizer OSU6162 in alcohol dependence: a retrospective secondary analysis. 酒精依赖患者焦虑的遗传倾向和对单胺稳定剂OSU6162的治疗反应:一项回顾性的二次分析
IF 3.6 3区 医学
Pharmacological Reports Pub Date : 2025-06-01 Epub Date: 2025-03-12 DOI: 10.1007/s43440-025-00707-8
Mun-Gwan Hong, Lotfi Khemiri, Joar Guterstam, Johan Franck, Nitya Jayaram-Lindström, Philippe A Melas
{"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}
引用次数: 0
Molecular mechanisms underlying the effects of statins on bone metabolism: an evolving paradigm of statins delivery modalities for bone regeneration. 他汀类药物对骨代谢影响的分子机制:他汀类药物用于骨再生的递送方式的演变范式。
IF 3.6 3区 医学
Pharmacological Reports Pub Date : 2025-06-01 Epub Date: 2025-04-01 DOI: 10.1007/s43440-025-00716-7
Randa Mohammed Zaki, Mohamed A M Ali, Mayada Said, Anis Ahmad Chaudhary, Fehmi Boufahja, Obaid Afzal, Abdelghafar M Abu-Elsaoud, Alyaa S Abdel Halim
{"title":"Molecular mechanisms underlying the effects of statins on bone metabolism: an evolving paradigm of statins delivery modalities for bone regeneration.","authors":"Randa Mohammed Zaki, Mohamed A M Ali, Mayada Said, Anis Ahmad Chaudhary, Fehmi Boufahja, Obaid Afzal, Abdelghafar M Abu-Elsaoud, Alyaa S Abdel Halim","doi":"10.1007/s43440-025-00716-7","DOIUrl":"10.1007/s43440-025-00716-7","url":null,"abstract":"<p><p>Statins, recognized for their lipid-lowering capabilities, have demonstrated osteoanabolic and anti-resorptive effects on bone metabolism. The effects encompass the overexpression of bone morphogenetic proteins, heightened osteoblast activity, and the control of inflammation. Nevertheless, conventional systemic administration of statins has difficulties, including restricted bone bioavailability and possible adverse effects. Recent improvements in targeted and localized drug delivery are revolutionizing the therapeutic landscape for statins in bone applications. This review consolidates existing knowledge regarding the molecular processes by which statins influence bone metabolism and describes novel drug delivery methods such as nano-carriers, biomaterial scaffolds, and controlled-release systems. It seeks to address current knowledge deficiencies and offer insights into how enhanced bioavailability and specificity can optimize the efficiency of statins in bone regeneration. The review integrates molecular insights with novel pharmacological strategies to inform future research and clinical applications, pinpointing critical areas for exploration, such as optimal dose, delivery safety, and clinical efficacy.</p>","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":" ","pages":"624-644"},"PeriodicalIF":3.6,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143754111","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}
引用次数: 0
Potential drug-drug interactions analysis in Polish pediatric hemato-oncologic unit, including acute lymphoblastic leukemia patients. 波兰儿科血液肿瘤科包括急性淋巴细胞白血病患者的潜在药物相互作用分析。
IF 3.6 3区 医学
Pharmacological Reports Pub Date : 2025-06-01 Epub Date: 2025-04-01 DOI: 10.1007/s43440-025-00719-4
Arkadiusz Adamiszak, Julia Drobińska, Izabela Niewiadomska-Wojnałowicz, Katarzyna Derwich, Edmund Grześkowiak, Agnieszka Bienert
{"title":"Potential drug-drug interactions analysis in Polish pediatric hemato-oncologic unit, including acute lymphoblastic leukemia patients.","authors":"Arkadiusz Adamiszak, Julia Drobińska, Izabela Niewiadomska-Wojnałowicz, Katarzyna Derwich, Edmund Grześkowiak, Agnieszka Bienert","doi":"10.1007/s43440-025-00719-4","DOIUrl":"10.1007/s43440-025-00719-4","url":null,"abstract":"<p><strong>Background: </strong>The lack of information on drug-drug interactions in the pediatric population significantly complicates making effective therapeutic decisions. Our study aimed to analyze the rate and risk factors as well as present potential drug-drug interactions (pDDIs) specifically for pediatric patients from the pediatric hemato-oncologic unit, including acute lymphoblastic leukemia (ALL) patients.</p><p><strong>Methods: </strong>We conducted a six-month prospective study in which clinical pharmacists examined medical records once a week to look for pDDIs using the Lexicomp<sup>®</sup> Drug Interactions Checker. Spearman's rank coefficient, logistic regression, and the U-Mann-Whitney test were used to identify correlations, analyze risk factors for pDDIs, and compare ALL patients with non-ALL patients, respectively. Recommendations were provided for the D and X pDDIs categories.</p><p><strong>Results: </strong>We identified 507 pDDIs in 119 screened patients, 388 of which were clinically relevant. Nearly 68% of the patients were exposed to at least one significant interaction. The number of pDDIs was positively correlated with the number of medications (r<sub>s</sub>=0.75, p < 0.001), off-label used drugs (r<sub>s</sub>=0.42, p < 0.001), comorbidities (r<sub>s</sub>=0.21, p = 0.019), and hospitalization length (r<sub>s</sub>=0.48, p < 0.001). The multivariate analysis revealed that at least 7 administered medications (OR = 8.63; 95% CI = 2.92-25.47) and 13 days in the hospital (OR = 3.47; 95% CI = 1.31-9.19) were risk factors for pDDIs. Furthermore, patients treated for ALL represent an at-risk group with a statistically higher number of drugs taken and pDDIs identified.</p><p><strong>Conclusions: </strong>Limited data on drug-drug interactions in the pediatric population emphasizes the need for close collaboration between clinical pharmacists and clinicians to improve the safety and effectiveness of pharmacotherapy.</p>","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":" ","pages":"751-760"},"PeriodicalIF":3.6,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143754114","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}
引用次数: 0
Carvacrol in asthma management: a comprehensive review of its therapeutic potential and mechanisms of action. 香芹酚在哮喘治疗中的应用:对其治疗潜力和作用机制的全面综述。
IF 3.6 3区 医学
Pharmacological Reports Pub Date : 2025-06-01 Epub Date: 2025-03-11 DOI: 10.1007/s43440-025-00709-6
Deepa Neopane, Poonam Kushwaha
{"title":"Carvacrol in asthma management: a comprehensive review of its therapeutic potential and mechanisms of action.","authors":"Deepa Neopane, Poonam Kushwaha","doi":"10.1007/s43440-025-00709-6","DOIUrl":"10.1007/s43440-025-00709-6","url":null,"abstract":"<p><p>Asthma, a chronic inflammatory disorder of the airways, remains a significant global health concern. Current treatments focus on symptom management and inflammation control, but the search for more effective and safer therapies continues. Carvacrol, a naturally occurring monoterpenoid phenol found in essential oils of various plants, has emerged as a promising bioactive compound with potent anti-inflammatory, antioxidant, and bronchodilatory properties. This review explores the potential of carvacrol as a novel therapeutic agent for asthma management. We discuss its mechanisms of action, including modulation of inflammatory pathways, inhibition of oxidative stress, and relaxation of bronchial muscles. Additionally, preclinical and clinical studies evaluating the efficacy and safety of carvacrol in asthma treatment are analyzed. The integration of carvacrol into existing treatment regimens could offer a multifaceted approach to asthma management, enhancing therapeutic outcomes and improving patients' quality of life.</p>","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":" ","pages":"610-623"},"PeriodicalIF":3.6,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143605900","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}
引用次数: 0
New pharmacological approaches in the treatment of schizophrenia. 精神分裂症治疗的新药理学方法。
IF 3.6 3区 医学
Pharmacological Reports Pub Date : 2025-06-01 Epub Date: 2025-04-08 DOI: 10.1007/s43440-025-00722-9
Józef Muszyński, Agnieszka Bienert, Rasha Wafaie Elsorady, Filip Rybakowski
{"title":"New pharmacological approaches in the treatment of schizophrenia.","authors":"Józef Muszyński, Agnieszka Bienert, Rasha Wafaie Elsorady, Filip Rybakowski","doi":"10.1007/s43440-025-00722-9","DOIUrl":"10.1007/s43440-025-00722-9","url":null,"abstract":"<p><p>Schizophrenia is a primary health concern, imposing a significant burden on both patients and healthcare systems globally. It is a disease with a complex etiology in which both genetic and environmental factors are involved. Despite numerous studies, the mechanism of its origin is still not fully understood. The hypotheses are synaptic, serotonergic, muscarinic, dopaminergic, microRNA-related, and neurodegenerative theories. Treatment to date is mainly based on antipsychotic drugs that act on the dopaminergic system. Although they are effective in reducing positive symptoms, their effect on negative and cognitive symptoms is limited, and their use is often associated with numerous side effects. A breakthrough in the treatment of schizophrenia came with the approval of the first drug with a non-dopaminergic mechanism of action, which opens up new therapeutic possibilities. As a result, there is intensive research into innovative substances that could increase the effectiveness of treatment and improve the quality of life of patients. In this review, we present the current state of knowledge about schizophrenia, its prevalence, risk factors, and its impact on patients' functioning. We pay special attention to new therapeutic directions, including drugs that affect systems other than the dopaminergic one, which could open up new prospects for treating the condition.</p>","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":" ","pages":"561-575"},"PeriodicalIF":3.6,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143811812","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}
引用次数: 0
Eribulin exerts multitarget antineoplastic activity in glioma cells. 艾力布林对胶质瘤细胞具有多靶点抗肿瘤活性。
IF 3.6 3区 医学
Pharmacological Reports Pub Date : 2025-06-01 Epub Date: 2025-03-08 DOI: 10.1007/s43440-025-00711-y
Guilherme Augusto Sousa Alcântara, Mariane Cristina do Nascimento, Livia Bassani Lins de Miranda, Bruna Oliveira de Almeida, Keli Lima, Eduardo Magalhães Rego, Leticia Veras Costa-Lotufo, João Agostinho Machado-Neto
{"title":"Eribulin exerts multitarget antineoplastic activity in glioma cells.","authors":"Guilherme Augusto Sousa Alcântara, Mariane Cristina do Nascimento, Livia Bassani Lins de Miranda, Bruna Oliveira de Almeida, Keli Lima, Eduardo Magalhães Rego, Leticia Veras Costa-Lotufo, João Agostinho Machado-Neto","doi":"10.1007/s43440-025-00711-y","DOIUrl":"10.1007/s43440-025-00711-y","url":null,"abstract":"<p><strong>Background: </strong>Gliomas, particularly glioblastomas, are highly aggressive cancers with rapid proliferation and poor prognosis. Current treatments have limited efficacy, highlighting the need for new therapeutic strategies. Eribulin mesylate, a synthetic macrocyclic ketone, has shown potential as an anticancer agent in several malignancies. This study investigates the cellular and molecular effects of eribulin in glioma models, focusing on its impact on cell cycle progression, apoptosis, mitochondrial function, and migration.</p><p><strong>Methods: </strong>Glioma cell lines were treated with eribulin. Cell viability was measured by MTT assay, and the cell cycle was analyzed by flow cytometry. Apoptosis was assessed through morphological changes, PARP1 cleavage, and γH2AX expression. Mitochondrial integrity and reactive oxygen species levels were evaluated by flow cytometry. Cell migration was assessed using a spheroid-based assay, and protein expression changes were analyzed by Western blotting.</p><p><strong>Results: </strong>Eribulin reduced cell viability, with HOG cells exhibiting the highest sensitivity. Cell cycle analysis showed G<sub>2</sub>/M phase arrest and morphological examination revealed polyploidy and apoptotic features. Mitochondrial dysfunction was observed, with decreased mitochondrial membrane potential and increased reactive oxygen species, particularly in HOG and T98G cells. Molecular analysis indicated activation of apoptotic pathways (PARP1 cleavage and γH2AX elevation) and reduced stathmin 1 expression. Eribulin also significantly reduced cell migration in HOG cells.</p><p><strong>Conclusion: </strong>Eribulin demonstrates potent anti-glioma effects through apoptosis, mitochondrial dysfunction, and cell cycle disruption. These findings support its potential as a therapeutic option for glioblastoma treatment, warranting further investigation into its mechanisms and clinical applicability.</p>","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":" ","pages":"817-828"},"PeriodicalIF":3.6,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143582285","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}
引用次数: 0
The metabolism of big endothelin-1 axis and lipids affects carotid atherosclerotic plaque stability - the possible opposite effects of treatment with statins and aspirin. 大内皮素-1轴和脂质的代谢影响颈动脉粥样硬化斑块的稳定性-可能与他汀类药物和阿司匹林治疗相反。
IF 3.6 3区 医学
Pharmacological Reports Pub Date : 2025-06-01 Epub Date: 2025-03-10 DOI: 10.1007/s43440-025-00714-9
Adam Płoński, Anna Krupa, Dariusz Pawlak, Katarzyna Sokołowska, Beata Sieklucka, Marcin Gabriel, Adam Filip Płoński, Jerzy Głowiński, Krystyna Pawlak
{"title":"The metabolism of big endothelin-1 axis and lipids affects carotid atherosclerotic plaque stability - the possible opposite effects of treatment with statins and aspirin.","authors":"Adam Płoński, Anna Krupa, Dariusz Pawlak, Katarzyna Sokołowska, Beata Sieklucka, Marcin Gabriel, Adam Filip Płoński, Jerzy Głowiński, Krystyna Pawlak","doi":"10.1007/s43440-025-00714-9","DOIUrl":"10.1007/s43440-025-00714-9","url":null,"abstract":"<p><strong>Background: </strong>The understanding of endothelin's role in carotid plaque instability is limited. We have studied the big endothelin-1 (ET-1) axis and its role in carotid plaque stability in patients undergoing carotid endarterectomy (CEA). The interactions of endothelins with known CVD risk factors were also evaluated.</p><p><strong>Methods: </strong>We studied 77 patients, who were divided into subgroups based on the optimal cut-off for grey-scale median (GSM), a marker of plaque instability. GSM values < 46.87 were designated as unstable carotid plaque, while GSM ≥ 46.87 were assigned to stable plaque. Twelve people without carotid atherosclerosis served as controls. Big ET-1, ET-1 and ET-1 (1-31) were measured and the endothelin-converting enzyme-1 (ECE-1) and chymase activity were calculated. Clinical and laboratory parameters were also evaluated.</p><p><strong>Results: </strong>ET-1 levels and ECE-1 activity were increased in all patient groups compared to controls (all P < 0.001) - and were higher in patients with unstable plaque than in those with stable plaque (P < 0.01). ET-1 (1-31) did not differ between the groups. ET-1 levels and ECE-1 activity inversely correlated with total cholesterol, LDL-cholesterol, and GSM values, whereas GSM was positively associated with total cholesterol and LDL fractions. Detailed analysis of patients according to the pharmacotherapy used revealed that statins favored ET-1 formation independently of cholesterol-lowering properties, whereas aspirin reduced this effect.</p><p><strong>Conclusions: </strong>ET-1 formation is the main pathway of big ET-1 metabolism in patients with carotid atherosclerosis, especially in those with plaque instability. Statins and aspirin appear to have opposing effects on ET-1 formation, suggesting the greater benefit related to plaque stability in patients taking both drugs concomitantly.</p>","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":" ","pages":"739-750"},"PeriodicalIF":3.6,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12066377/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143597546","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}
引用次数: 0
Compound PZ-1262, a 4-isoquinoline-sulfonamide analog of Brexpiprazole, produces potential antidepressant, anxiolytic and procognitive effects in rodent models. 化合物PZ-1262是Brexpiprazole的4-异喹啉磺胺类似物,在啮齿动物模型中具有潜在的抗抑郁、抗焦虑和促进认知的作用。
IF 3.6 3区 医学
Pharmacological Reports Pub Date : 2025-06-01 Epub Date: 2025-03-11 DOI: 10.1007/s43440-025-00713-w
Anna Partyka, Joanna Gołębiowska, Krzysztof Marciniec, Vittorio Canale, Wojciech Trybała, Grzegorza Satała, Katarzyna Grychowska, Magdalena Jastrzębska-Więsek, Andrzej J Bojarski, Agnieszka Nikiforuk, Władysława A Daniel, Anna Wesołowska, Paweł Zajdel, Piotr Popik
{"title":"Compound PZ-1262, a 4-isoquinoline-sulfonamide analog of Brexpiprazole, produces potential antidepressant, anxiolytic and procognitive effects in rodent models.","authors":"Anna Partyka, Joanna Gołębiowska, Krzysztof Marciniec, Vittorio Canale, Wojciech Trybała, Grzegorza Satała, Katarzyna Grychowska, Magdalena Jastrzębska-Więsek, Andrzej J Bojarski, Agnieszka Nikiforuk, Władysława A Daniel, Anna Wesołowska, Paweł Zajdel, Piotr Popik","doi":"10.1007/s43440-025-00713-w","DOIUrl":"10.1007/s43440-025-00713-w","url":null,"abstract":"<p><strong>Background: </strong>Novel antipsychotics are characterized by multitarget profile of action, affecting among others, dopamine and serotonin receptors. In a series of experiments, we designed, synthesized and examined two new isoquinoline-sulfonamide analogs of the modern multitarget antipsychotics aripiprazole and brexpiprazole, compounds PZ-1262 and PZ-1264. We hypothesized that the 4-isoquinolinesulfonamide moiety, derived from the structure of 5-HT<sub>6</sub> receptor antagonists, would provide compounds with enhanced activity at 5-HT<sub>6</sub> receptors, along with partial agonistic activity at 5-HT<sub>1A</sub> and D<sub>2</sub> receptors.</p><p><strong>Methods: </strong>The receptor binding profile, functional activity, and metabolic stability of PZ-1262 and PZ-1264 were evaluated through in vitro assays. Potential antipsychotic, antidepressant, anxiolytic, and pro-cognitive effects were assessed using in vivo behavioral tests in rodents.</p><p><strong>Results: </strong>In vitro, PZ compounds demonstrated partial agonistic activity at 5-HT<sub>1A</sub> receptor, antagonistic activity at D<sub>2</sub> and D<sub>3</sub> as well as 5-HT<sub>2A</sub>, 5-HT<sub>6</sub> and 5-HT<sub>7</sub> receptors and metabolic stability. In vivo, both compounds enhanced phencyclidine-induced hyperactivity in rats and decreased immobility time in the forced swim test in mice, without influencing spontaneous locomotor activity. In the novel object recognition test in rats, they demonstrated pro-cognitive effects in phencyclidine disturbed conditions. PZ-1262 potentiated D-amphetamine-induced hyperactivity, exhibited anxiolytic-like effects in the four plates test in mice, and demonstrated significant brain penetration.</p><p><strong>Conclusions: </strong>The complex pharmacodynamic profile translated into the useful psychotropic effects. While the compounds potentiated D-amphetamine- and phencyclidine-induced hyperactivity, this action could be regarded as a desired activating effect rather than evidence against antipsychotic-like efficacy. Present findings point to PZ-1262 as a more promising lead compound for further research.</p>","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":" ","pages":"689-702"},"PeriodicalIF":3.6,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143597541","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}
引用次数: 0
Effects of 3,5,4'-tri-[4-(nitrooxy)butanoyl]oxy resveratrol, a new nitric oxide-releasing derivative of resveratrol, on platelet activation. 白藜芦醇的一种新的一氧化氮释放衍生物3,5,4'-三-[4-(硝基)丁醇]氧白藜芦醇对血小板活化的影响。
IF 3.6 3区 医学
Pharmacological Reports Pub Date : 2025-06-01 Epub Date: 2025-02-25 DOI: 10.1007/s43440-024-00691-5
Giuseppe Guglielmini, Emanuela Berardi, Federica Messina, Maria Carla Marcotullio, Paolo Gresele
{"title":"Effects of 3,5,4'-tri-[4-(nitrooxy)butanoyl]oxy resveratrol, a new nitric oxide-releasing derivative of resveratrol, on platelet activation.","authors":"Giuseppe Guglielmini, Emanuela Berardi, Federica Messina, Maria Carla Marcotullio, Paolo Gresele","doi":"10.1007/s43440-024-00691-5","DOIUrl":"10.1007/s43440-024-00691-5","url":null,"abstract":"<p><strong>Background: </strong>Resveratrol is a polyphenol of red wine that is thought to contribute to the \"French paradox\" by protecting against atherosclerotic cardiovascular events. It has anti-inflammatory and antioxidant properties and enhances nitric oxide (NO) production. However, in conditions of severe endothelial dysfunction, its cardiovascular protective effects may be limited. Our study aimed to synthesize and characterize a new nitro derivative of resveratrol, trinitroresveratrol (TN-RSV), for its potential nitric oxide-donating and antiplatelet effects.</p><p><strong>Methods: </strong>3,5,4'-tri-[4-(nitrooxy)butanoyl]oxy resveratrol (TN-RSV) was synthetized starting from commercial resveratrol (RSV) through the intermediacy of 3,5,4'-tri-(4-bromo-butanoyl)oxy resveratrol. Platelet aggregation was assessed by light transmission aggregometry (LTA) using collagen as agonist. The release of nitric oxide (NO) from TN-RSV or from activated platelets was assessed as the concentration of the NO degradation products (nitrites plus nitrates, NOx) in the supernatant. Platelet adhesion to collagen under flow conditions was assessed using a parallel plate perfusion chamber. Reactive oxygen species (ROS) production from collagen-activated platelets was assessed by flow cytometry using the fluorescent probe H2DCFDA.</p><p><strong>Results: </strong>TN-RSV spontaneously released NO and significantly inhibited collagen-induced platelet aggregation in a dose-dependent manner. This effect was greater than that of resveratrol and it was not affected by the preincubation with L-NAME, a nitric-oxide synthase (NOS) inhibitor, indicating that TN-RSV directly inhibits platelet activation independently of NOS.</p><p><strong>Conclusions: </strong>Our findings suggest that TN-RSV has potential as an antiplatelet agent and that further research exploring its therapeutic applications for conditions associated with endothelial dysfunction and platelet hyperreactivity is warranted.</p>","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":" ","pages":"729-738"},"PeriodicalIF":3.6,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143493096","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}
引用次数: 0
0
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
相关产品
×
本文献相关产品
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:604180095
Book学术官方微信