Pharmacology Research & Perspectives最新文献_第2页

Pharmacogenetic Study of Anti-TB Drugs in the Native Ancestry Peruvian Population. 秘鲁土著祖先人群抗结核药物的药理学研究。

IF 2.9 4区医学

Pharmacology Research & Perspectives Pub Date : 2025-06-01 DOI: 10.1002/prp2.70135

Luis Jaramillo-Valverde, Mary K Horton, Julio A Poterico, Cristina M Lanata, Heinner Guio

{"title":"Pharmacogenetic Study of Anti-TB Drugs in the Native Ancestry Peruvian Population.","authors":"Luis Jaramillo-Valverde, Mary K Horton, Julio A Poterico, Cristina M Lanata, Heinner Guio","doi":"10.1002/prp2.70135","DOIUrl":"10.1002/prp2.70135","url":null,"abstract":"In Peru, 33 113 individuals were diagnosed with tuberculosis (TB) in 2023. While TB treatments are generally effective, 3.4% to 13% of cases are associated with significant adverse drug reactions, with drug-induced liver injury (DILI) being the most prevalent. Limited data exist on genetic risk factors for DILI in Latin America; even less is known about these factors in native Peruvian populations. This study aimed to determine the prevalence of TB drug-metabolizing genotypes in these populations. A cross-sectional analysis was conducted using genetic data from 254 participants from the Peruvian Genome Project (PGP) representing three subpopulations: Coast, Andes, and Amazon. Twenty-three genes associated with TB treatment, include isoniazid, rifampin, ethambutol, and pyrazinamide, as identified in the PharmGKB database, were analyzed. Significant differences were observed in genotype frequencies among subpopulations for AGBL4, NAT2, GSTP1, SLCO1B1, NOS, and CYP2B6 genes. The Amazonian population demonstrated a higher risk of DILI due to the increased prevalence of hepatotoxic alleles in AGBL4, GSTP1, and SLCO1B1. In contrast, alleles in the NOS gene indicated a lower risk of hepatotoxicity in the Andean population. However, the high-risk genotypes identified in the study's native Peruvian populations exhibit distinct prevalence patterns compared to those reported in the 1000 Genomes Project. These findings can inform the development of personalized therapeutic strategies to improve TB treatment outcomes among Peru's diverse subpopulations.","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":"13 3","pages":"e70135"},"PeriodicalIF":2.9,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12167507/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144302708","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Psychotropic Polypharmacy and QT Prolonging Medications in Hospitalized Patients. 住院患者的精神药物综合用药和QT延长药物。

IF 2.9 4区医学

Pharmacology Research & Perspectives Pub Date : 2025-06-01 DOI: 10.1002/prp2.70107

Joel Moore, Isabella Singh, Ruby Tszwai Au, Genevieve Gabb, Joanne Eng-Frost, Elizabeth Hotham, Sepehr Shakib, Vijayaprakash Suppiah

{"title":"Psychotropic Polypharmacy and QT Prolonging Medications in Hospitalized Patients.","authors":"Joel Moore, Isabella Singh, Ruby Tszwai Au, Genevieve Gabb, Joanne Eng-Frost, Elizabeth Hotham, Sepehr Shakib, Vijayaprakash Suppiah","doi":"10.1002/prp2.70107","DOIUrl":"10.1002/prp2.70107","url":null,"abstract":"It is common for patients with mental illnesses to be prescribed multiple psychotropic medications to effectively manage their conditions. Psychotropic polypharmacy has been shown to potentiate and increase the risks of several adverse effects, including QT prolongation. This study aimed to investigate the prescribing trends of and differences in prescribing of QT-prolonging medications (QTPMs) at admission and discharge in hospitalized patients. This retrospective observational study utilized inpatient data from three public hospitals between January and December 2019. QTPMs were classified according to the AZCERT classification. QTPMs doses were evaluated by calculating the ratio of prescribed daily dose (PDD) to the defined daily dose (DDD). Subgroup analyses showed significant differences between patient groups on admission and discharge (all p < 0.001). Mean QTPMs decreased significantly between the two time points only in patients admitted to acute medical and geriatric units (p < 0.001). PDD/DDD ratio for conditional risk QTPMs in acute mental health unit (AMHU) patients was increased at discharge (p = 0.038). Patients admitted to acute medical and geriatric units were four and eight times more likely to be discharged with one QTPM with known risk in combination with more QTPMs with conditional risk. Logistic regression showed significant relationships with age and total number of regular medicines at admission for those prescribed high-dose QTPMs at discharge. The findings underscore the necessity for enhanced monitoring of QTPMs in hospitalized patients, particularly for those at higher risk.","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":"13 3","pages":"e70107"},"PeriodicalIF":2.9,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12041124/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144047832","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Rapidly Polymerizing Click Hydrogel Provides Localized Delivery of rhBMP2 to Promote Bone Formation. 快速聚合Click水凝胶提供rhBMP2的局部递送促进骨形成。

IF 2.9 4区医学

Pharmacology Research & Perspectives Pub Date : 2025-06-01 DOI: 10.1002/prp2.70119

D Joshua Cohen, Thomas W Jacobs, D Scott Wilson, Michael C Mancini, Christine Van Duyn, Zvi Schwartz, Barbara D Boyan

{"title":"Rapidly Polymerizing Click Hydrogel Provides Localized Delivery of rhBMP2 to Promote Bone Formation.","authors":"D Joshua Cohen, Thomas W Jacobs, D Scott Wilson, Michael C Mancini, Christine Van Duyn, Zvi Schwartz, Barbara D Boyan","doi":"10.1002/prp2.70119","DOIUrl":"10.1002/prp2.70119","url":null,"abstract":"Delivery of bioactive agents to achieve tissue regeneration at targeted sites with minimal side effects requires the use of biodegradable carriers and sustained release of the therapeutic at appropriate concentrations. We developed a copper-free polyethylene glycol-based click hydrogel to deliver bone morphogenetic protein-2 (BMP2), a potent regulator for bone regeneration that is currently delivered to orthotopic sites using an absorbable collagen sponge, leading to a burst release of BMP2, potentially causing ectopic bone formation. In contrast, the hydrogel is delivered as a liquid, conforming to the contours of treatment sites, polymerizing rapidly at body temperature without generating heat, exhibiting minimal swelling after gelation, and releasing its payload as it degrades. We assessed the safety and effectiveness of BMP2 delivery in vitro and in mouse cranial defects in vivo, comparing it to BMP2 delivered via a collagen sponge. No toxicity was observed in vitro or systemically, nor was there allergic sensitization caused by the hydrogel in rabbits. Released BMP2 increased the production of osteogenic markers in vitro. Hydrogel + BMP2 caused equivalent defect closure and total bone growth compared to collagen + BMP2; however, there was more vascularization within the defect but less bone growth outside of the defect on the calvaria for hydrogel + BMP2 compared to collagen + BMP2. In conclusion, the click hydrogels used in this study are safe and effective for administering BMP2 with fewer undesired off-target effects and high potential to be used with BMP2 for bone regeneration, supporting the use of click chemistry hydrogels to deliver bioactive agents to treatment sites safely and effectively.","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":"13 3","pages":"e70119"},"PeriodicalIF":2.9,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12146212/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144249143","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

In Vitro Signaling Properties of Cannabinoid and Orexin Receptors: How Orexin Receptors Influence Cannabinoid Receptor-Mediated Signaling. 大麻素和食欲素受体的体外信号特性：食欲素受体如何影响大麻素受体介导的信号传导。

IF 2.9 4区医学

Pharmacology Research & Perspectives Pub Date : 2025-04-01 DOI: 10.1002/prp2.70078

Kawthar A Mohamed, Robert B Laprairie

{"title":"In Vitro Signaling Properties of Cannabinoid and Orexin Receptors: How Orexin Receptors Influence Cannabinoid Receptor-Mediated Signaling.","authors":"Kawthar A Mohamed, Robert B Laprairie","doi":"10.1002/prp2.70078","DOIUrl":"10.1002/prp2.70078","url":null,"abstract":"The co-expression of different types of G protein-coupled receptors (GPCRs) in the same cells can have implications for receptor signaling and receptor cross-talk, potentially altering the apparent potency or efficacy of ligands targeting each receptor. The endocannabinoid and orexinergic systems, consisting of class A GPCRs and their endogenous ligands, are highly complex and regulate processes such as appetite, sleep, nociception, and energy homeostasis. The shared anatomical distribution of cannabinoid and orexin receptors in various regions of the central nervous system (CNS), coupled with data from previous studies exploring physical and functional interactions between these receptors, suggests that the endocannabinoid and orexinergic systems engage in crosstalk. In this study, we explored how orexin receptors (OX1, OX2) altered the in vitro signaling of cannabinoid receptors (CB1, CB2) in Chinese hamster ovary (CHO)-K1 cells by quantifying cyclic adenosine monophosphate (cAMP) inhibition and βarrestin2 recruitment. Our results suggest that orexin receptors alter agonist-dependent signaling at the cannabinoid receptors by enhancing cannabinoid receptor-mediated cAMP inhibition while increasing or decreasing cannabinoid receptor-mediated βarrestin2 recruitment. These initial results are important for understanding the effects associated with cannabinoid ligands and may provide novel insights for therapeutics targeting physiological processes modulated by both systems.","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":"13 2","pages":"e70078"},"PeriodicalIF":2.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11860274/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143503191","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The Chicken Embryo: An Alternative Animal Model in Development, Disease and Pharmacological Treatment. 鸡胚：一种发育、疾病和药理治疗的替代动物模型。

IF 2.9 4区医学

Pharmacology Research & Perspectives Pub Date : 2025-04-01 DOI: 10.1002/prp2.70086

Oykum Kaplan-Arabaci, Zuzana Dančišinová, Ragnhild Elisabeth Paulsen

{"title":"The Chicken Embryo: An Alternative Animal Model in Development, Disease and Pharmacological Treatment.","authors":"Oykum Kaplan-Arabaci, Zuzana Dančišinová, Ragnhild Elisabeth Paulsen","doi":"10.1002/prp2.70086","DOIUrl":"10.1002/prp2.70086","url":null,"abstract":"To examine various medications and substances, in vivo models such as rats and mice are routinely used. However, it is utterly desirable to reduce extensive amounts of animals for these experimental models, which are costly and time-consuming. Animals are frequently put through a variety of procedures that could cause them pain, distress, or even harm; therefore, it is important to think about the ethical ramifications of using them in research. Thus, by following the three R's of animal research: reduction, replacement, and refinement, living animals used in studies should be minimized. The embryo of Gallus gallus, the domestic chicken, is a great model to research many different diseases and conditions. Its efficient blood supply from the chorioallantoic membrane gives us a unique possibility to administer chemicals or cells to the embryo in a noninvasive manner. In this review, we evaluate some advantages and disadvantages of using the developing chicken as an alternative in vivo model for development, disease, and pharmacological treatment. We focus on the top two leading causes of death: neurological disorders and cancer. We present a number of studies that describe the use of the chicken embryo in neuroscience and neurodevelopment research, in cancer research, and pharmacodynamic and pharmacokinetic studies. These studies show that the chicken embryo is an inexpensive, readily available, self-sufficient model with a short incubation period, high accessibility, and ideal for drug screening, making it an appealing model that can provide insightful biological and pharmacological information.","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":"13 2","pages":"e70086"},"PeriodicalIF":2.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11925699/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143670453","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

β-Adrenergic Blockers Increase cAMP and Stimulate Insulin Secretion Through a PKA/RYR2/TRPM5 Pathway in Pancreatic β-Cells In Vitro. β-肾上腺素能阻滞剂通过PKA/RYR2/TRPM5途径增加胰腺β-细胞cAMP并刺激胰岛素分泌

IF 2.9 4区医学

Pharmacology Research & Perspectives Pub Date : 2025-04-01 DOI: 10.1002/prp2.70092

Naoya Murao, Risa Morikawa, Yusuke Seino, Kenju Shimomura, Yuko Maejima, Yuichiro Yamada, Atsushi Suzuki

{"title":"β-Adrenergic Blockers Increase cAMP and Stimulate Insulin Secretion Through a PKA/RYR2/TRPM5 Pathway in Pancreatic β-Cells In Vitro.","authors":"Naoya Murao, Risa Morikawa, Yusuke Seino, Kenju Shimomura, Yuko Maejima, Yuichiro Yamada, Atsushi Suzuki","doi":"10.1002/prp2.70092","DOIUrl":"https://doi.org/10.1002/prp2.70092","url":null,"abstract":"β-adrenergic blockers (β-blockers) are extensively used to inhibit β-adrenoceptor activation and subsequent cAMP production in many cell types. In this study, we characterized the effects of β-blockers on mouse pancreatic β-cells. Unexpectedly, high concentrations (100 μM) of β-blockers (propranolol and bisoprolol) paradoxically increased cAMP levels 5-10 fold, enhanced Ca2+ influx, and stimulated a 2-4 fold increase in glucose- and glimepiride-induced insulin secretion in MIN6-K8 clonal β-cells and isolated mouse pancreatic islets. These effects were observed despite minimal expression of β-adrenoceptors in these cells. Mechanistically, the cAMP increase led to ryanodine receptor 2 (RYR2) phosphorylation via protein kinase A (PKA), triggering Ca2+-induced Ca2+ release (CICR). CICR then activates transient receptor potential cation channel subfamily M member 5 (TRPM5), resulting in increased Ca2+ influx via voltage-dependent Ca2+ channels. These effects contradict the conventional understanding of the pharmacology of β-blockers, highlighting the variability in β-blocker actions depending on the experimental context.","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":"13 2","pages":"e70092"},"PeriodicalIF":2.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11994265/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144010766","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The TAAR1 Agonist PCC0105004 Regulates Amygdala Synaptic Plasticity to Alleviate Anxiety-Like Behaviors in Rats. TAAR1激动剂PCC0105004调节大鼠杏仁核突触可塑性以减轻焦虑样行为

IF 2.9 4区医学

Pharmacology Research & Perspectives Pub Date : 2025-04-01 DOI: 10.1002/prp2.70068

Yingtian Zhang, Wei Zhang, Linyao Yu, Yaoqin Shi, Min Xu, Hui Wang, Chunmei Li, Jingwei Tian

{"title":"The TAAR1 Agonist PCC0105004 Regulates Amygdala Synaptic Plasticity to Alleviate Anxiety-Like Behaviors in Rats.","authors":"Yingtian Zhang, Wei Zhang, Linyao Yu, Yaoqin Shi, Min Xu, Hui Wang, Chunmei Li, Jingwei Tian","doi":"10.1002/prp2.70068","DOIUrl":"10.1002/prp2.70068","url":null,"abstract":"Anxiety disorder is a persistent, widespread, and intractable mood disorder, and the available pharmacotherapies have limited efficacy with significant side effects. Trace amine-associated receptor 1 (TAAR1) is an emerging drug target for neuropsychiatric disorders. This study examined the effects and underlying mechanisms of a novel TAAR1 agonist, PCC0105004, in a rat model of CUMS-induced anxiety-like behavior. The elevated zero maze and open field tests test were employed to evaluate the anti-anxiety-like activity of PCC0105004. PCC0105004 dose-dependently attenuated anxiety-like behaviors in rats without affecting spontaneous activity. Morphologically, PCC0104005 decreased the density of dendritic spines in the amygdala. For the mechanistic studies, whole-genome transcriptomic analysis revealed significant differences in the patterns of amygdala gene expression in the CUMS-induced anxiety rat model. These transcriptomic data were further confirmed by using RT-qPCR and western blotting, further revealing alterations associated with genes (Col1a1, DCN, Ewsr1) known to regulate synaptic plasticity, and PCC0105004 was able to reverse these changes. These results suggest that PCC0105004 is a promising anxiolytic candidate for pharmacotherapy of anxiety and warrants further examination and development.","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":"13 2","pages":"e70068"},"PeriodicalIF":2.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11971484/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143788748","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Exploring Cordycepin as a Neuroprotective Agent in Huntington's Disease: In Vitro and In Vivo Insights. 探索将虫草素作为亨廷顿舞蹈症的神经保护剂：体外和体内观察。

IF 2.9 4区医学

Pharmacology Research & Perspectives Pub Date : 2025-04-01 DOI: 10.1002/prp2.70091

Chih-Wei Tung, Siew Chin Chan, Pei-Hsun Cheng, Yi-Ching Chen, Po-Ming Wu, Wei-Chen Lin, Rong-Jane Chen, Bu-Miin Huang, Shang-Hsun Yang

{"title":"Exploring Cordycepin as a Neuroprotective Agent in Huntington's Disease: In Vitro and In Vivo Insights.","authors":"Chih-Wei Tung, Siew Chin Chan, Pei-Hsun Cheng, Yi-Ching Chen, Po-Ming Wu, Wei-Chen Lin, Rong-Jane Chen, Bu-Miin Huang, Shang-Hsun Yang","doi":"10.1002/prp2.70091","DOIUrl":"10.1002/prp2.70091","url":null,"abstract":"Huntington's disease (HD) is a challenging neurodegenerative disorder linked to Huntingtin (HTT) gene mutation, lacking an effective cure despite numerous therapeutic attempts. Cordyceps sinensis, recognized for its health benefits, particularly its constituent cordycepin, exhibits neuroprotective effects in various neurodegenerative diseases. However, the neuroprotective potential of cordycepin in HD remains insufficiently explored. In this study, in vitro experiments using HD cell models demonstrate that cordycepin treatment enhances cell survival, slightly diminishes mutant HTT aggregates, and improves neuronal formation. In vivo investigations on R6/2 HD transgenic mice reveal a modest increase in body weight and a slight amelioration in pathological aggregates following cordycepin administration, although behavioral changes are not significant. While the underlying mechanisms remain unexplored, the findings suggest cordycepin's promise as a supplementary therapeutic for HD, providing neuroprotective effects and reducing mutant protein aggregates.","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":"13 2","pages":"e70091"},"PeriodicalIF":2.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11979966/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143811818","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Analysis of Reporting Trends of Serious Adverse Events Associated With Anti-Obesity Drugs. 抗肥胖药物相关严重不良事件报告趋势分析。

IF 2.9 4区医学

Pharmacology Research & Perspectives Pub Date : 2025-04-01 DOI: 10.1002/prp2.70080

Branislava B Raičević, Andrej Belančić, Nikola Mirković, Slobodan M Janković

{"title":"Analysis of Reporting Trends of Serious Adverse Events Associated With Anti-Obesity Drugs.","authors":"Branislava B Raičević, Andrej Belančić, Nikola Mirković, Slobodan M Janković","doi":"10.1002/prp2.70080","DOIUrl":"10.1002/prp2.70080","url":null,"abstract":"Concern over the side effects of anti-obesity medications, particularly if severe, has grown as their use has increased. Thus, the objective was to use trends in the reporting of suspected adverse events associated with anti-obesity medications that have been approved for sale in the European Union to attempt to uncover discrepancies in the safety of these medications. The study was designed as secondary research, based on data about the number of adverse drug reactions (both serious and non-serious) reported to the EudraVigilance database. Trends of the annual reporting rates for the six anti-obesity drugs were analyzed by the Joinpoint Trend Analysis Software that divides the trendline into an optimum number of segments connected by \"joinpoints\" and tests the significance of the trend within each segment. The trends of serious adverse drug events showed clear differences among the anti-obesity drugs: while all drugs had significant increasing trends during a few initial years after their appearance on the market, only the annual number of reports for semaglutide continued to grow ever since (annual change + 67.1%, p = 0.000). On the contrary, a continuous increase in the reporting rate of non-serious adverse drug events was observed only for liraglutide (annual change + 33.8%, p = 0.000) while for the other anti-obesity drugs, including semaglutide, the trends after the initial period were either negative or did not increase significantly. In conclusion, among the anti-obesity drugs currently approved, only semaglutide shows a continuously increasing trend in the annual reporting of serious adverse events, suggesting a need for further investigation of safety signals.","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":"13 2","pages":"e70080"},"PeriodicalIF":2.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11850437/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143493098","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Soluble Guanylate Cyclase Stimulator, BAY41-8543: A Promising Approach for the Treatment of Chronic Heart Failure Caused by Pressure and Volume Overload. 可溶性鸟苷酸环化酶刺激剂BAY41-8543：一种治疗压力和容量过载引起的慢性心力衰竭的有前途的方法。

IF 2.9 4区医学

Pharmacology Research & Perspectives Pub Date : 2025-04-01 DOI: 10.1002/prp2.70087

Adriana Martišková, Matúš Sýkora, Natália Andelová, Miroslav Ferko, Olga Gawrys, Katarína Andelová, Petr Kala, Luděk Červenka, Barbara Szeiffová Bačová

{"title":"Soluble Guanylate Cyclase Stimulator, BAY41-8543: A Promising Approach for the Treatment of Chronic Heart Failure Caused by Pressure and Volume Overload.","authors":"Adriana Martišková, Matúš Sýkora, Natália Andelová, Miroslav Ferko, Olga Gawrys, Katarína Andelová, Petr Kala, Luděk Červenka, Barbara Szeiffová Bačová","doi":"10.1002/prp2.70087","DOIUrl":"10.1002/prp2.70087","url":null,"abstract":"Heart failure (HF) is a leading cause of morbidity and mortality, often driven by prolonged exposure to pathological stimuli such as pressure and volume overload. These factors contribute to excessive oxidative stress, adverse cardiac remodeling, and dysregulation of the nitric oxide-soluble guanylate cyclase-cyclic guanosine monophosphate (NO-sGC-cGMP) signaling pathway. Given the urgent need for effective treatments, this study investigated the potential of sGC stimulators to mitigate HF progression. We utilized male hypertensive Ren-2 transgenic (TGR) rats and a volume-overload HF model induced by an aortocaval fistula (ACF). Rats received the sGC stimulator BAY 41-8543 (3 mg/kg/day) for 30 weeks, while normotensive Hannover Sprague-Dawley rats served as controls. At the study endpoint (40 weeks of age), left ventricular tissue was analyzed using mass spectrometry, Western blotting, and histological assessment. TGR rats treated with sGC stimulators exhibited a significant increase in key antioxidant proteins (SOD1, CH10, ACSF2, NDUS1, DHE3, GSTM2, and PCCA), suggesting enhanced resistance to oxidative stress. However, sGC stimulator treatment also upregulated extracellular matrix remodeling markers (MMP-2, TGF-β, and SMAD2/3), which are typically associated with fibrosis. Despite this, Masson's trichrome staining revealed reduced collagen deposition in both TGR and TGR-ACF rats receiving sGC stimulators. Notably, all untreated TGR-ACF rats succumbed before the study endpoint, preventing direct assessment of sGC stimulator effects in advanced HF. These findings highlight the therapeutic potential of sGC stimulators in HF, particularly through their antioxidant effects. However, their concurrent influence on fibrosis warrants further investigation to optimize treatment strategies.","PeriodicalId":19948,"journal":{"name":"Pharmacology Research & Perspectives","volume":"13 2","pages":"e70087"},"PeriodicalIF":2.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11955242/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143753426","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0