Pharmacological Reports最新文献

{"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-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":"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}

{"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}

{"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":"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":"670-688"},"PeriodicalIF":3.6,"publicationDate":"2025-06-01","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":"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":"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":"703-715"},"PeriodicalIF":3.6,"publicationDate":"2025-06-01","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":"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":"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":"800-808"},"PeriodicalIF":3.6,"publicationDate":"2025-06-01","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":"Calycosin and kidney health: a molecular perspective on its protective mechanisms.","authors":"Diksha Dalal, Lovedeep Singh, Anish Singh","doi":"10.1007/s43440-025-00728-3","DOIUrl":"https://doi.org/10.1007/s43440-025-00728-3","url":null,"abstract":"<p><p>Kidney diseases encompass a diverse group of pathological conditions characterized by the progressive loss of renal function, leading to systemic complications and increased morbidity. Their global prevalence increasing, posing a substantial public health challenge. The underlying pathophysiology involves complex molecular interactions that drive inflammation, fibrosis, and tissue injury. Notably, the AGE/RAGE axis activates NF-κB, a pivotal transcription factor responsible for pro-inflammatory cytokine production. This response is further intensified by NLRP3-inflammasome activation, which detects cellular stress and promotes IL-1β release. Additionally, TGF-β signaling through SMADs and MAPK pathways induces ECM accumulation, contributing to tissue fibrosis. Besides this, oxidative stress-induced ferroptosis and apoptosis also play critical roles in disease progression. Given the multifactorial nature of kidney diseases, agents with multi-targeted actions are promising for effective renoprotection. Significant research interest has emerged in exploring calycosin's protective effects against kidney-related pathologies, owing to its diverse pharmacological properties, including anti-inflammatory, antioxidant, anti-apoptotic, and anti-fibrotic effects. Calycosin is a naturally occurring isoflavone primarily found in Astragalus membranaceus, a well-known medicinal herb in traditional Chinese medicine. Several studies have demonstrated that calycosin exerts its renoprotective effects by modulating key molecular mediators, including RAGE, NF-κB, TGF-β, MAPKs, NLRP3-inflammasome, Nrf-2, PPARγ, and Sirtuin-3, among others, thereby providing a multitargeted defense against kidney diseases. Considering the potential of calycosin in modulating these mediators, the present study was conceptualized to study the mechanistic interplay underlying its renoprotective effects. By investigating these interconnected pathways, this study will provide foundational insights that will enable future researchers to address existing gaps and further elucidate calycosin's potential in renal disorders.</p>","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":"77 3","pages":"658-669"},"PeriodicalIF":3.6,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144041997","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":"Unveiling the role of Na⁺/K⁺-ATPase pump: neurodegenerative mechanisms and therapeutic horizons.","authors":"Ramandeep Kaur Sidhu, Kousik Maparu, Shamsher Singh, Khadga Raj Aran","doi":"10.1007/s43440-025-00717-6","DOIUrl":"10.1007/s43440-025-00717-6","url":null,"abstract":"<p><p>Sodium and potassium-activated adenosine 5'-triphosphatase (Na+/K+-ATPase) is a pivotal plasma membrane enzyme involved in neuronal activity and cellular homeostasis. The dysregulation of these enzymes has been implicated in a spectrum of neurodegenerative disorders like Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and neurodevelopmental disorders including autism spectrum disorder (ASD), psychiatric disorders such as schizophrenia, and neurological problems like epilepsy. A hallmark of these disorders is the gradual loss of neuronal integrity and function, often exacerbated by protein accumulation within brain cells. This review delves into the multifaceted role of Na⁺/K⁺-ATPase dysfunction in driving oxidative stress, excitotoxicity, and neuroinflammation, contributing to synaptic and neuronal damage. Emerging therapeutic strategies, such as gene therapy and developing isoform-specific enzyme modulators, offer promising avenues for targeted interventions. Furthermore, this review highlights innovative research directions, including the role of Na⁺/K⁺-ATPase in synaptic plasticity, the identification of endogenous regulators, and its contribution to neuroinflammatory pathways. Personalized medicine and advanced gene-editing technologies are positioned as transformative tools for crafting safer and more precise therapies tailored to individual patients. This comprehensive exploration underscores the enzyme's therapeutic potential and sets the stage for developing novel targeted strategies to mitigate the burden of Na⁺/K⁺-ATPase-linked neurological disorders.</p>","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":" ","pages":"576-592"},"PeriodicalIF":3.6,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143674078","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":"Blockade of IgG Fc receptors reduces pain after intervertebral disc injury.","authors":"Xiaoyou Shi, Peyman Sahbaie, Tian-Zhi Guo, Yen-Ming Hsu, Wade S Kingery, J David Clark","doi":"10.1007/s43440-025-00720-x","DOIUrl":"10.1007/s43440-025-00720-x","url":null,"abstract":"<p><strong>Background: </strong>Intervertebral disc (IVD) injury is a common cause of low back pain and disability. Recent evidence suggests that autoantibodies contribute to such pain. We, therefore, explored the hypothesis that a novel IgG Fc receptor blocker could reverse chronic pain-related behaviors in a mouse model of IVD injury.</p><p><strong>Methods: </strong>These studies used a multi-level lumbar IVD puncture model of low back pain in male C57BL/6 mice. Additional mouse strains evaluated included Fc gamma chain knockouts failing to express excitatory IgG Fc receptors and muMT mice incapable of producing mature B lymphocytes or antigen-specific IgG. Nociceptive testing consisted of hindpaw mechanical allodynia and pinch hyperalgesia. The expression of FcgrI and FcgrIII excitatory IgG Fc receptors and FcgrIIb inhibitory receptors was measured in lumbar sensory ganglia and spinal cord tissue using qPCR. The accumulation of IgG was measured using immunoblotting.</p><p><strong>Results: </strong>After disc injury, wild-type mice developed chronic hindpaw mechanical allodynia and pinch hyperalgesia. At 10 weeks post-injury, FcgrI, FcgrIIb and FcgrIII receptor expression were all increased in lumbar sensory ganglia and lumbar spinal cord tissue. Disc injury also caused IgG deposition at 10 weeks in the injured tissues and corresponding spinal cord. Treating disc-injured mice with the pan IgG Fc receptor interacting molecule (PRIM) reversed pain behaviors.</p><p><strong>Conclusions: </strong>Injury of mouse IVDs leads to persistent nociceptive sensitization in mice which can be reduced by administration of PRIM. Blockade of IgG Fc receptors may be a viable approach to the treatment of low back pain.</p>","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":" ","pages":"809-816"},"PeriodicalIF":3.6,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143731227","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":"Probiotics: a promising future in the treatment of ulcerative colitis?","authors":"Larissa Zambom Côco, Eduarda de Souza Belisário, Elisardo Corral Vasquez, Thiago Melo Costa Pereira, Rafaela Aires, Bianca Prandi Campagnaro","doi":"10.1007/s43440-025-00724-7","DOIUrl":"https://doi.org/10.1007/s43440-025-00724-7","url":null,"abstract":"<p><p>Ulcerative colitis is an idiopathic and chronic inflammatory bowel disease, characterized by inflammation of the mucosa of the colon and rectum. Clinical manifestations commonly include abdominal pain, diarrhea (with or without hematochezia), and weight loss. The pathogenesis of ulcerative colitis is multifactorial, involving a combination of genetic predispositions and lifestyle factors. High consumption of processed food, sedentary habits, alcohol intake, and stress are among the lifestyle factors implicated in disease onset and progression. Current treatment strategies focus on managing symptoms and inducing remission, however, the chronic nature of the disease, along with the adverse effects of conventional therapies, often compromises patient's quality of life. Therefore, exploring alternative therapies that can prolong remission and reduce symptom burden is important. Experimental evidence suggests that probiotics may extend remission duration in ulcerative colitis. Moreover, probiotics exhibit efficacy in amelioration clinical symptoms by reducing inflammation markers, preserving, and restoring intestinal epithelial. This review explores the advantages of the administration of probiotics in the treatment of ulcerative colitis, elucidating their mechanism of action.</p>","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":"77 3","pages":"645-657"},"PeriodicalIF":3.6,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143975045","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":"Polypharmacology: new drugs in 2023-2024.","authors":"Piotr Ryszkiewicz, Barbara Malinowska, Eberhard Schlicker","doi":"10.1007/s43440-025-00715-8","DOIUrl":"10.1007/s43440-025-00715-8","url":null,"abstract":"<p><p>Polypharmacology is an emerging approach to drug design and development that involves the use of multi-target-directed ligands (MTDLs), agents capable of interacting with multiple biological targets simultaneously. The effective treatment of chronic and multifactorial conditions, driven by the dysregulation of multiple interconnected pathways, such as cancer, autoimmune and metabolic disorders, cardiovascular and neurodegenerative diseases, is one of the most substantial challenges in contemporary pharmacology. 'Traditional' single-target-based treatment frequently shows limited effectiveness, as resistance to therapy develops or relapses occur. The rational use of MTDLs seems therefore a promising way to address the complexity of biological systems, feedback mechanisms, crosstalk, and molecular pathways. Many MTDLs have been successfully marketed to date. Moreover, plenty of them offer an additional benefit in comparison to 'traditional' treatment approaches. To assess whether the polypharmacological trend remains prevalent, we thoroughly analysed drugs approved in the years of 2023-2024 in Germany. Among 73 newly introduced substances, 18 are in line with the polypharmacology concept, including 10 antitumor agents, 5 drugs indicated for autoimmune disorders, 1 indicated for hand eczema, 1 antidiabetic (and anti-obesity) drug, and 1 modified corticosteroid.</p>","PeriodicalId":19947,"journal":{"name":"Pharmacological Reports","volume":" ","pages":"543-560"},"PeriodicalIF":3.6,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12066383/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143649963","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}