Pharmacological Reports最新文献

{"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":"https://doi.org/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":""},"PeriodicalIF":3.6,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Investigating whether alcohol is transformed to norepinephrine or dopamine in the mouse brain.","authors":"Piotr Wlaź, Paul J Fitzgerald, Paweł Żmudzki, Katarzyna Socała","doi":"10.1007/s43440-025-00708-7","DOIUrl":"https://doi.org/10.1007/s43440-025-00708-7","url":null,"abstract":"<p><strong>Background: </strong>A number of rodent studies have investigated the effects of alcohol (ethanol) administration on the catecholaminergic neurotransmitters, norepinephrine (NE) and dopamine (DA). These studies suggest that presentation of alcohol to mice or rats can alter brain levels of NE and DA, in various subregions. Other studies have presented the hypothesis that there may be an unidentified pathway in rodents, and other organisms, that actually transforms ethanol to NE or DA. Here, this paper investigates the hypothesis in male CD-1 mice.</p><p><strong>Methods: </strong>Experimental mice were systemically injected with an intoxicating dose of stable isotope-labeled carbon 13 (C13) ethanol (ethanol-1-¹³C, 20% v/v, 1.5 g/kg, ip), and brain samples (hippocampus and brainstem) were collected two hours post-injection. Two other groups of mice received normal unlabeled carbon 12 (C12) ethanol or a water (Control) injection, respectively.</p><p><strong>Results: </strong>Although we had difficulty detecting the two neurotransmitters (especially C13 NE) due to their very low concentrations, high-resolution mass spectrometry analysis suggests that C12 ethanol selectively boosted hippocampal C12 NE, and C13 ethanol likewise boosted hippocampal C13 NE. We did not observe effects on DA.</p><p><strong>Conclusions: </strong>These data provide preliminary information on whether there is a novel biosynthetic pathway in mice that converts alcohol to catecholamines in select brain regions, where the ethanol molecule would presumably help form the ethanolamine side chain of NE. There are, however, alternative interpretations of these findings, including that acute alcohol administration modulates catecholamine release, reuptake, metabolism, or canonical biosynthesis.</p>","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143605945","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":"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":"https://doi.org/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":""},"PeriodicalIF":3.6,"publicationDate":"2025-03-11","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}

{"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":"https://doi.org/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-HT₆ receptor antagonists, would provide compounds with enhanced activity at 5-HT₆ receptors, along with partial agonistic activity at 5-HT_1A and D₂ 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_1A receptor, antagonistic activity at D₂ and D₃ as well as 5-HT_2A, 5-HT₆ and 5-HT₇ 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":""},"PeriodicalIF":3.6,"publicationDate":"2025-03-11","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}

{"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":"https://doi.org/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":""},"PeriodicalIF":3.6,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Juvenile fluoxetine treatment affects the maturation of the medial prefrontal cortex and behavior of adolescent female rats.","authors":"Joanna Kryst, Agnieszka Chocyk, Anna Solarz-Andrzejewska, Iwona Majcher-Maślanka","doi":"10.1007/s43440-025-00712-x","DOIUrl":"https://doi.org/10.1007/s43440-025-00712-x","url":null,"abstract":"<p><strong>Background: </strong>Serotonin is strongly involved in the regulation of brain development, including the proper formation of neuronal circuits and synaptic plasticity. One of the factors that can affect brain serotonin levels is exposure to fluoxetine (FLX), a selective serotonin reuptake inhibitor, the first-line pharmacological treatment for depression and anxiety in the pediatric population. The safety of early-life FLX treatment is still questionable. Women are more prone to anxiety and depression from a young age. We hypothesized that juvenile FLX treatment influences the brain maturation and behavior of adolescent females.</p><p><strong>Methods: </strong>On postnatal days 20 to 28, juvenile female rats were injected once daily with FLX. Five days later, anxiety- and fear-related behaviors and amphetamine-induced locomotor activity were assessed. On postnatal day 40, the numbers of neurons and glial cells in the medial prefrontal cortex (mPFC) and hippocampus were estimated via stereological methods. Additionally, the mRNA expression of cell survival/apoptosis and synaptic plasticity markers was evaluated via RT‒qPCR.</p><p><strong>Results: </strong>FLX-treated females showed decreased anxiety level, freezing behavior during fear conditioning and amphetamine-induced locomotor activity when compared to control females. Simultaneously, FLX-injected females presented greater regional volume and numbers of neurons and astrocytes in specific subregions of the mPFC when compared to the control group. Additionally, FLX-treated females showed increased expression of genes regulating cell survival and reduced mRNA levels of AMPA glutamate receptors in the mPFC.</p><p><strong>Conclusions: </strong>Juvenile FLX affects the maturation of the mPFC and attenuates anxiety-like behavior, fear memory and the locomotor response to amphetamine in adolescent females.</p>","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143597545","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":"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 G₂/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":""},"PeriodicalIF":3.6,"publicationDate":"2025-03-08","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}

{"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":"https://doi.org/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":""},"PeriodicalIF":3.6,"publicationDate":"2025-02-25","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}

{"title":"A single dose of haloperidol decanoate induces short-term hippocampal neuroinflammation: focus on the glial response.","authors":"Izaviany Schmitz, Larissa Daniele Bobermin, Amanda da Silva, Fernanda Becker Weber, Natalie K Thomaz, Felipe Schmitz, Morgana Brondani, Roselei Fachinetto, Guilhian Leipnitz, Angela T S Wyse, Carlos-Alberto Gonçalves, André Quincozes-Santos","doi":"10.1007/s43440-025-00706-9","DOIUrl":"https://doi.org/10.1007/s43440-025-00706-9","url":null,"abstract":"<p><strong>Background: </strong>Haloperidol is a widely used antipsychotic for the treatment of neuropsychiatric disorders, the pathophysiology of which may involve hippocampal alterations. Hippocampus is affected by long-term use of the drug, but the effects of acute doses on the hippocampus remain unclear. The present study investigated whether a single dose of haloperidol decanoate could induce short-term hippocampal neuroinflammation and changes in cholinergic, glutamatergic and redox homeostasis in adult rats, focusing on the glial response.</p><p><strong>Methods: </strong>Male Wistar rats (60 days old) received a single intramuscular injection of haloperidol decanoate (38 mg/kg) or vehicle. After 7 days, hippocampal tissue was used to assess gene expression of inflammatory mediators, glutamate transporters, and transcriptional factors that regulate neuroinflammation. The enzymatic activities of acetylcholinesterase (AChE), glutamine synthetase (GS), and glutathione peroxidase (GPx), and glutamate uptake and reduced glutathione (GSH) levels were also determined.</p><p><strong>Results: </strong>Haloperidol decanoate increased the gene expression of pro-inflammatory cytokines, cyclooxygenase-2 (COX-2), and inducible nitric oxide synthase (iNOS). Moreover, downregulation of the transcriptional factor erythroid 2-related factor 2 (Nrf2) and the peroxisome proliferator-activated receptor-gamma coactivator (PGC-1α) was observed. In contrast, nuclear factor κB (NFκB) transcriptional levels remained unchanged. Haloperidol also increased glutamate uptake, the glutamate transporter GLAST gene expression, and the AChE and GPx activities.</p><p><strong>Conclusions: </strong>Our findings show that a single dose of haloperidol decanoate induces short-term hippocampal neuroinflammation and changes in glial parameters, highlighting the need for future adjuvant glioprotective strategies that can attenuate these effects.</p>","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143468138","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":"Comparative analysis of risedronate and its regioisomers synthesized via microwave-assisted method: bone affinity, cytotoxicity, permeability, and therapeutic potential.","authors":"Monika Zielińska, Amanda Pacholak, Bartosz Orwat, Mariusz Sandomierski, Ireneusz Kownacki, Ewa Kaczorek, Adam Voelkel","doi":"10.1007/s43440-025-00703-y","DOIUrl":"https://doi.org/10.1007/s43440-025-00703-y","url":null,"abstract":"<p><strong>Background: </strong>Bisphosphonates (BPs) are widely used for treating bone diseases such as osteoporosis due to their strong affinity for hydroxyapatite (HA) in bones. Minor structural variations among BPs can significantly affect their therapeutic potential. This study aimed to synthesize risedronate (RSD) and its two regioisomers (2-RSD, 4-RSD) and investigate the impact of these variations on bone affinity, permeability, and cytotoxicity.</p><p><strong>Methods: </strong>RSD and its regioisomers were synthesized using a microwave-assisted method. Bone affinity was assessed through sorption studies on HA and two polymer-ceramic materials mimicking bone properties. Compound permeability was predicted using the Parallel Artificial Membrane Permeability Assay (PAMPA). Cytotoxicity was evaluated by analyzing the response of bacterial cells to BPs using metabolic activity assays.</p><p><strong>Results: </strong>2-RSD demonstrated a higher bone affinity and similar permeability than commercially available RSD. 2-RSD also showed reduced cytotoxicity in bacterial cell assays, indicating enhanced biocompatibility. These findings suggest that minor structural changes can lead to significant differences in therapeutic efficacy.</p><p><strong>Conclusions: </strong>The study highlights the potential of the 2-RSD as a more effective treatment for bone diseases. Structural variations in BPs can greatly influence their biological properties, paving the way for the development of improved therapeutic agents.</p>","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143383062","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}