Naunyn-Schmiedeberg's archives of pharmacology最新文献

{"title":"UPLC-Q-TOF-MS and network pharmacology to reveal the mechanism of Guizhi Gegen decoction against type 2 diabetes mellitus.","authors":"Nini Jia, Jing Li, Mengyao Cui, Yaqing Li, Dayuan Jiang, Xiaoqin Chu","doi":"10.1007/s00210-025-04011-3","DOIUrl":"https://doi.org/10.1007/s00210-025-04011-3","url":null,"abstract":"<p><p>Type 2 diabetes mellitus (T2DM) is a chronic metabolic disease. Clinical studies have shown that the incidence and prevalence of T2DM has been on the rise globally in recent years, and the mortality rate is also increasing. Chinese herbs is multiple target for disease. Guizhi Gegen decoction (GZGGD) is one of the most alternative treatment for T2DM. However, the treatment mechanism is unclear. The composition of the GZGGD was determined by ultra-high-performance liquid chromatography with quadrupole time-of-flight mass spectrometry. The key targets and pathways were predicted by network pharmacology and molecular docking. In vivo experiments were performed to further verify and reveal the potential mechanism of action. We identified 44 active components of GZGGD (genistein, 26-hydroxyporicoic acid DM, puerarin, eugenol, and gentiobiose). Network pharmacology predicted key targets such as TNF, AKT1, TP53, EGFR, and STAT3, and AGE-RAGE, IL-17 signaling pathways were enriched. Molecular docking showed that the active components of GZGGD have good binding activity with the potential targets of T2DM. In vivo animal experiments showed improvement in white blood, fasting blood glucose, and inflammatory factor levels (INS, TC, TNF-α, and IL-6). This study clarifies the potential role of GZGGD in T2DM, which can help in the study of T2DM.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143649719","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":"Bromopride stimulates 5-HT₄-serotonin receptors in the human atrium.","authors":"Lina Maria Rayo Abella, Joachim Neumann, Britt Hofmann, Ulrich Gergs","doi":"10.1007/s00210-025-04013-1","DOIUrl":"https://doi.org/10.1007/s00210-025-04013-1","url":null,"abstract":"<p><p>Bromopride, an analogue of metoclopramide, is approved in some countries to treat gastrointestinal diseases. These therapeutic effects of bromopride are explained by antagonism at D₂-dopamine receptors in the gut and the brain. We tested here the hypothesis that bromopride acts as an agonist or antagonist at the human cardiac 5-HT₄-serotonin receptors. To this end, the force of contraction (FOC) was measured in isolated human atrial preparations (HAP), in isolated left atrial preparations (LA), and in isolated spontaneously beating right atrial (RA) preparations from mice with cardiac specific overexpression of the human 5-HT₄-serotonin receptors (5-HT₄-TG). Bromopride concentration dependently increased FOC in LA from 5-HT₄-TG. The positive inotropic effect (PIE) of bromopride in LA from 5-HT₄-TG was abolished by GR125487, a 5-HT₄-serotonin receptor antagonist. Only in the presence of the phosphodiesterase III inhibitor cilostamide did bromopride raise FOC under isometric conditions in HAP. The PIE of 10 µM bromopride in HAP was extinguished by 1 µM GR125487. When serotonin had elevated FOC in HAP, additionally applied bromopride reduced FOC. These data suggest that bromopride is a partial agonist at human cardiac 5-HT₄-serotonin receptors.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143649676","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":"Calycosin alleviates ovariectomy-induced osteoporosis by promoting BMSCs autophagy via the PI3K/Akt/mTOR pathway.","authors":"Shouyu Xiang, Yinji Luo, Wei Liu, Cheng Tang, Tianyu Zhu, Lai Tian, Tiansheng Zheng, Long Ling, Mingyang Jia, Xing Li, Yanming Cao","doi":"10.1007/s00210-025-04009-x","DOIUrl":"https://doi.org/10.1007/s00210-025-04009-x","url":null,"abstract":"<p><p>Calycosin, the main extract from the traditional Chinese medicine (TCM) Astragalus membranaceus, has demonstrated anti-osteoporotic properties in ovariectomized (OVX) mice. However, the specific pathways through which it prevents osteoporosis remain unexplored. This study aimed to investigate the pathways by which calycosin promotes autophagy in bone marrow mesenchymal stem cells (BMSCs) and alleviates ovariectomy-induced osteoporosis. Mice were divided into three groups: sham, OVX, and OVX + calycosin. Following a 12-week intervention period, assessments included analysis of bone microstructure, serum concentrations of LC3II and ALP, and evaluation of Trap expression in femoral tissue. Immunohistochemical staining was used to assess the expression levels of PI3K, Runx2, and Beclin-1 in bone tissue. Additionally, levels of Runx2, ALP, p-PI3K, PI3K, mTOR, p-mTOR, Beclin-1, and ULK1 were analyzed. Osteogenic differentiation of BMSCs was evaluated using ALP and Alizarin red staining. OVX significantly impaired BMSCs osteogenic differentiation, resulting in bone loss. In contrast, calycosin increased bone mass, promoted osteogenesis, and reduced cancellous bone loss. Parameters, such as BMD, BV/TV, Tb.N, and Tb.Th, were significantly higher in the OVX + calycosin group compared to the OVX group. Additionally, Tb.Sp was notably reduced in the OVX + calycosin group. Calycosin also upregulated levels of Runx2, ALP, p-PI3K, p-mTOR, ULK1, and Beclin-1. In cellular studies, calycosin promoted BMSCs osteogenesis under OVX conditions; however, this effect was inhibited by LY294002. Calycosin effectively combats bone loss and improves bone structure. Its mechanism likely involves the promotion of autophagy in osteoblasts, thereby stimulating BMSC osteogenic differentiation. This effect may be mediated through the PI3K/Akt/mTOR pathway. These findings suggest that calycosin has the potential to serve as an alternative therapy for treating osteoporosis.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143634156","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":"Ligandrol lowers endurance and negatively affects lipid and hormonal profile of male rats.","authors":"Veselin Vasilev, Katerina Georgieva, Desislava Arabadzhiyska, Slavi Delchev, Fanka Gerginska, Marina Komrakova, Kai O Boeker, Arndt F Schilling, Nikolay Boaydjiev","doi":"10.1007/s00210-025-04028-8","DOIUrl":"https://doi.org/10.1007/s00210-025-04028-8","url":null,"abstract":"<p><p>Selective androgen receptor modulators are currently not approved but are widely used in gyms. In the present study, the effects of ligandrol and its combination with endurance training on functional and clinically important parameters were studied in male healthy rats. Fourteen-week-old male rats were divided into four groups: two training (40 min, 5 times/week) and two non-training (5 min, 3 times/week). The velocity was 25 m/min at a track elevation of 5° for all groups. Ligandrol (0.4 mg/kg body weight, 5 times/week) was administered to one training and one non-training group and vehicle to the other groups (n = 10 per group) for 8 weeks. We conducted functional tests and examined morphometric, functional, hematological, hormonal, and clinical chemistry indicators in rats and histological and gene expression analyses in gastrocnemius muscle. Endurance training had a positive effect on all functional tests and increased vascular endothelial growth factor a (Vegf-a) gene expression. Ligandrol treatment reduced submaximal endurance, maximal oxygen consumption, concentrations of glucose, follicle-stimulating hormone, and testosterone. It increased grip strength, triglycerides, and total cholesterol concentrations and had no effect on maximal sprinting speed, maximal time to exhaustion, hematological and morphometric parameters, and gene expression of myostatin and insulin-like growth factor 1. The negative effects of ligandrol treatment outweighed its benefits in this study. Endurance training alone had favorable effects, and its combination with ligandrol did not seem to have an advantage. In the training group, ligandrol decreased Vegf-a gene expression and the size of muscle fibers type I and IIa.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143634163","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":"Unlocking the therapeutic potential of the NFAT pathway in kidney diseases.","authors":"Shruti Shreya, Neha Dagar, Anil Bhanudas Gaikwad","doi":"10.1007/s00210-025-04033-x","DOIUrl":"https://doi.org/10.1007/s00210-025-04033-x","url":null,"abstract":"<p><p>The nuclear factor of activated T cells (NFAT) is a novel renoprotective transcription factor in an inactive form in the cytoplasm and an active form in the nucleus. NFAT is expressed in T cells, heart, kidney and lymphocytes. NFAT plays an essential role in inducing apoptosis of renal tubular epithelial cells. NFAT levels have been observed to increase significantly during kidney diseases. Further, downregulation or silencing of endogenous NFAT mitigates kidney diseases. NFAT regulation depends upon the intricate interplay between calcium ions and calcineurin (CaN), thus orchestrating the NFAT/calcineurin signalling pathway. When CaN is activated, it induces dephosphorylation of NFAT and localises the active NFAT into the nucleus, which ultimately leads to inflammation, fibrosis and apoptosis of kidney cells. Further, the global incidence (> 800 million) due to kidney disease imposes a significant economic burden on the healthcare system. Therefore, it is crucial to comprehend the pathways involved in the pathophysiology of kidney diseases to develop targeted interventions. Ongoing studies indicate potential therapies, including anandamide, 11R-VIVIT and maxacalcitol to regulate NFAT levels in kidney disease. The present review discusses the role and regulation of NFAT in the pathogenesis of kidney diseases. This is focused on various preclinical studies that have shown NFAT downregulation as a potential therapeutic strategy against kidney disease setting the foundation for future clinical investigations.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143634301","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":"Nanomicelle curcumin improves oxidative stress, inflammatory markers, and assisted reproductive techniques outcomes in endometriosis cases: a randomized clinical trial.","authors":"Rahil Jannatifar, Elham Asa, Ebrahim Cheraghi, Atefeh Verdi","doi":"10.1007/s00210-025-03958-7","DOIUrl":"https://doi.org/10.1007/s00210-025-03958-7","url":null,"abstract":"<p><p>We studied the effect nanomicelle curcumin on oxidative stress markers, pro-inflammatory cytokines, and assisted reproductive techniques (ART) outcomes in endometriosis cases. This randomized controlled trial was conducted on 50 women with endometriosis at the age of 25-35 candidate for ART referred to Roya Infertility Center in Qom, Iran, 2022. The participants were allocated to intervention (n = 25) and control (n = 25) groups by the blocked randomization method. Nanomicelle curcumin with a dose of 120 mg per day was given to the intervention group twice a day for 10 weeks, and the placebo with the same dose was given to the control group. Follicular fluid (FF) samples were collected from women with endometriosis stage III/IV undergoing ART. Antioxidant enzyme (MDA, SOD, CAT, and TAC) and pro-inflammatory cytokines (IL-8 and TNF-a) were tested. ART results such as (number of oocyte received, high-quality embryo, and pregnancy outcomes) were compared between two groups. Increased serum levels of TAC, CAT, and SOD were observed after nanomicelle curcumin treatment. Furthermore, FF levels of MDA, IL-8, and TNF-a reduced significantly after treatment in nanomicelle curcumin. Nanomicelle curcumin supplementation led to an improved number of oocytes retrieved, number of mature (MII) oocytes, fertilization, cleavage, and high-quality embryos. Nanomicelle curcumin treatment can modulate stress oxidative and inflammation in endometriosis-induced infertile patients. ART outcomes also improved after nanomicelle curcumin therapy. Our results suggest that nanomicelle curcumin can be a therapeutic target for infertile patients with endometriosis.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143634167","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":"Neuroprotective effects of semaglutide and metformin against rotenone-induced neurobehavioral changes in male diabetic rats.","authors":"Esraa A Salem, Saad Misfer Alqahtani, Ehab A M El-Shoura, Sameh S Zaghlool, Lobna A Abdelzaher, Sally A M Mohamed, Ibrahim S Alalhareth, Alzahraa A M Sheref","doi":"10.1007/s00210-025-03920-7","DOIUrl":"https://doi.org/10.1007/s00210-025-03920-7","url":null,"abstract":"<p><p>Pre-existing diabetes raises the likelihood of Parkinson's disease (PD), according to epidemiological and animal research. Our study aimed to investigating the likely neuroprotective effect of metformin (Met) and/or semaglutide (Sem) in model of PD in male diabetic rats and the possible underlying mechanism. Type 2 diabetes (T2DM) was induced by giving high-fat diet (HFD) for 3 weeks followed by a single streptozotocin (STZ) injection (40 mg/kg, i.p., once dose) followed by injection of 9 doses of rotenone every 48 ± 2 h for induction of PD. Met and/or Sema were administered to DM+PD via gastric gavage once daily for 4 weeks. In comparison with the DM+PD group, Met and/or Sem significantly lowered blood glucose levels, HOMA-IR, HbA1C, cholesterol, triglycerides, and LDL with significantly increased insulin and HDL levels. In addition, there was enhanced brain antioxidant status with lower oxidative-inflammatory stress biomarkers associated with improved rat cognitive, locomotor, and olfactory functions. A significant downregulation of caspase 3 and GFAP with concomitant upregulation of NRF2 protein expressions were observed in treated groups. Overall, co-treatment with Met and Sem elicited more efficacy than that of the individual regimen. When combined, the results of this study have demonstrated for the first time that Met and Sem work in concert to create neuroprotection in PD model of male diabetic rats compared to when taken separately. The study's findings indicate that Met and/or Sem have a restorative effect on T2DM and PD-induced changes in neurobehavioral and biochemical/molecular indices ascribed to the improvement of endogenous antioxidant systems, decreased lipid peroxidation, suppression of oxidative/inflammatory stress, and-most importantly-regulation of Nrf2 and caspase 3.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143634181","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":"Protective effect of histatin 5 and amphotericin B conjugated nanostructures in C. albicans challenged Swiss albino mice.","authors":"Saraswathi Nagaraj, Shoba Narayan","doi":"10.1007/s00210-025-03997-0","DOIUrl":"https://doi.org/10.1007/s00210-025-03997-0","url":null,"abstract":"<p><p>This study explores the development of silica-gold nanostructures conjugated with histatin 5 (H5) and amphotericin B (A_mpB) for the management of Candida albicans-induced candidiasis. H5 and A_mpB were covalently attached to the silica-gold nanostructures (ASi_np-GN) using EDC-NHS chemistry, with fluorescent FITC labeling employed in a parallel experiment to study nanostructure localization. Characterization techniques, including UV-Vis spectroscopy, dynamic light scattering, zeta potential analysis, fluorescence spectroscopy, differential scanning calorimetry, thermogravimetric analysis, high-resolution transmission electron microscopy, atomic force microscopy, and drug release studies, confirmed the successful conjugation and stability of the nanostructures. Biological evaluations using C. albicans demonstrated a minimum inhibitory concentration (MIC50) of 5.42 μM for A_mpB in the nanostructures, along with enhanced localization as observed via fluorescence microscopy. The nanostructures effectively inhibited biofilm formation and showed high biocompatibility in hemolysis and MTT assays. In vivo studies using a disseminated candidiasis model in Swiss albino mice revealed significant therapeutic efficacy, evidenced by reduced C. albicans burden, decreased A_mpB toxicity, improved heart function, and preserved tissue integrity. These results highlight the role of H5 conjugation in targeted drug delivery, enhancing the therapeutic potential of A_mpB while minimizing adverse effects, making it a promising approach for candidiasis management. However, a detailed pharmacokinetic investigation on the use of these nanostructures is warranted before taking this to the clinical side.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143634199","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":"Using cluster analysis to investigate consumption patterns in cases positive to ketamine: a national 7-year study.","authors":"Shyh-Yuh Wei, Chien-Chou Su, Hsuan-Yun Hu, Chih-Hsin Pan","doi":"10.1007/s00210-025-04019-9","DOIUrl":"https://doi.org/10.1007/s00210-025-04019-9","url":null,"abstract":"<p><p>The use of ketamine has increased; however, actual consumption patterns and ketamine-related deaths remain poorly understood. This study aimed to (1) cluster the consumption patterns of individuals who consume ketamine and (2) investigate their associations with manner and cause of death. A retrospective study was conducted on all cases positive to ketamine at death, retrieved from the Institute of Forensic Medicine between 2013 and 2019. A total of 414 individuals tested positive for ketamine in various samples, including blood, pleural effusion, hair, and others, with 294 individuals having detectable ketamine in their blood samples, which were subsequently clustered. The most prevalent patterns identified were ketamine plus alcohol (49.5%), ketamine plus new psychoactive substances (39.1%), and ketamine plus methamphetamine (24.4%). Drug intoxication was the most reported cause of death, followed by traffic accidents. Cluster 1 exhibited moderate ketamine concentrations (1.7 µg/mL), a high prevalence of polydrug use (85%), and an increased risk of suicide. Cluster 4 displayed very low ketamine concentrations (0.13 µg/mL) but similarly high rates of polydrug use (85%) and an elevated risk of accidental death. The concurrent use of ketamine and alcohol, primarily categorized within cluster 3, accounted for nearly half of the deaths resulting from drug intoxication or traffic accidents. Our study underscores the potential dangers of using ketamine as one of multiple substances. Our study also emphasized the critical role that consumption patterns and dosages play in determining the potential lethal outcomes associated with ketamine. In the future, medical applications of ketamine must consider patients' use of other substances and inform them of the associated risks.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143630647","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":"Ubrogepant, erenumab, and eptinezumab antagonize positive inotropic effects of the calcitonin gene-related peptide in the isolated human atrium.","authors":"Joachim Neumann, Britt Hofmann, Ulrich Gergs","doi":"10.1007/s00210-025-04029-7","DOIUrl":"https://doi.org/10.1007/s00210-025-04029-7","url":null,"abstract":"<p><p>The calcitonin gene-related peptide (CGRP) is an endogenous peptide that is known to be involved in the development of a migraine. CGRP is also present in the human heart, acts via CGRP receptors, and has been shown to increase the force of contraction (FOC) in isolated, electrically driven human atrial preparations (HAP) from adult patients obtained during open-heart surgery. Here, the hypothesis was tested that the positive inotropic effect (PIE) of CGRP could be attenuated by three anti-migraine drugs, namely ubrogepant, erenumab (both CGRP receptor antagonists), and eptinezumab (a CGRP antagonist). CGRP, cumulatively applied at concentrations ranging from 1 to 100 nM, increased the FOC. In the presence of cilostamide, an inhibitor of phosphodiesterase III, CGRP was more potent and effective than in the absence of cilostamide. Furthermore, when 100 nM CGRP was administered, subsequent application of ubrogepant (1 nM), erenumab (2 nM), and eptinezumab (6 nM) led to a reduction of FOC in HAP. In a more effective way, 1 µM carbachol and 1 µM (-)-N⁶-phenylisopropyladenosine (PIA) attenuated the PIE of CGRP in the presence of cilostamide. Conversely, when we applied first ubrogepant (1 nM), erenumab (2 nM), or eptinezumab (6 nM), then, this pre-incubation attenuated the PIE in HAP of cumulatively applied CGRP compared to CGRP given alone. We conclude that ubrogepant, erenumab, and eptinezumab are functional antagonists of CGRP in HAP at therapeutic concentrations of these anti-migraine drugs. Further investigation is necessary to determine whether this reduction in FOC is beneficial or detrimental for migraine patients.</p>","PeriodicalId":18876,"journal":{"name":"Naunyn-Schmiedeberg's archives of pharmacology","volume":" ","pages":""},"PeriodicalIF":3.1,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143630644","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}