Central nervous system agents in medicinal chemistry最新文献

{"title":"Cardiospermum halicacabum: A Scoping Review on its Phytoactives, Neuroprotective, Anti-Inflammatory, and Antioxidant Potential.","authors":"Himangi Vig, Anuradha Mishra, Ankita Wal","doi":"10.2174/0118715249382675251026140404","DOIUrl":"https://doi.org/10.2174/0118715249382675251026140404","url":null,"abstract":"<p><strong>Introduction: </strong>Cardiospermum halicacabum, commonly known as balloon vine or love in a puff, is a medicinal plant recognized for its diverse phytoactive compounds. This plant contains various bioactive constituents, including alkaloids like cardiospermin, flavonoids such as quercetin, and triterpenoids, which contribute to its therapeutic properties. This scoping review presents current literature on the neuroprotective, anti-inflammatory, and antioxidant potentials of Cardiospermum halicacabum, along with preclinical findings, patent reports, and commercially accessible formulations and nanoformulations.</p><p><strong>Method: </strong>This scoping review was conducted in accordance with the PRISMA-ScR guidelines. A comprehensive search of Web of Science, PubMed, Embase, Medline, Google Scholar, and Google Patents was conducted (2008-2024) using keywords such as Cardiospermum halicacabum, balloon vine, antioxidant, anti-inflammatory, and neuroprotective. Only English-language, peer-reviewed articles, patents, and commercially available formulations were included. Studies unrelated to the plant's neuroprotective, anti-inflammatory, or antioxidant mechanisms were excluded. Screening, data extraction, and critical appraisal were performed independently by three reviewers.</p><p><strong>Result: </strong>Studies suggest that Cardiospermum halicacabum exhibits significant neuroprotective effects, potentially due to its antioxidant activity, which protects neuronal cells from oxidative stressinduced damage. The plant's anti-inflammatory properties are well-documented, indicating efficacy in reducing inflammation through mechanisms that modulate cytokine production and inhibit inflammatory pathways. Its antioxidant constituents scavenge free radicals, preventing oxidative damage to cells and tissues that extends its potential applications in managing oxidative stressrelated disorders.</p><p><strong>Discussion: </strong>The findings highlight the promising therapeutic potential of Cardiospermum halicacabum in neuroprotection, anti-inflammatory responses, and oxidative stress management. While preclinical studies support its efficacy, further research, including clinical trials, is required to confirm its pharmacological benefits and optimize its therapeutic applications. The development of nanoformulations suggests an advanced approach to enhancing bioavailability and targeted drug delivery.</p><p><strong>Conclusion: </strong>Cardiospermum halicacabum shows promise as a multifaceted therapeutic agent, particularly in neurological and inflammatory conditions. Due to its antioxidant, anti-inflammatory, and neuroprotective properties, Cardiospermum halicacabum can be considered a potential neuroprotective agent. While preclinical data are encouraging, further clinical trials are necessary to validate its efficacy and safety for human use. Medicinal potential.</p>","PeriodicalId":93930,"journal":{"name":"Central nervous system agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147944052","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Translational Perspectives on Anti-Inflammatory Interventions for Neurodegenerative Disorders: Evidence from Gut-Brain Axis.","authors":"Vasundhara Saxena, Vishwadeep Singh, Sanskriti","doi":"10.2174/0118715249430752260407050033","DOIUrl":"https://doi.org/10.2174/0118715249430752260407050033","url":null,"abstract":"<p><p>The Gut-Brain Axis (GBA) has a complex role in chronic neuroinflammation, which is increasingly connected to neurodegenerative diseases (NDDs) such as Multiple Sclerosis (MS), Parkinson's Disease (PD), and Alzheimer's Disease (AD). Through neuronal, endocrine, and immunological pathways, the GBA enables twoway communication between the gastrointestinal tract and the central nervous system. According to recent research, the pathophysiology of neuroinflammatory responses in NDDs may be significantly influenced by gut dysbiosis, increased intestinal permeability, and modified microbial metabolites, such as Short-Chain Fatty Acids (SCFAs) and polyphenols. This study summarizes preclinical and clinical data supporting several anti- inflammatory approaches targeting GBA. Probiotics and fecal microbiota transplantation are two examples of microbiota-based treatments that have demonstrated promise in reducing neuroinflammatory responses and enhancing cognitive performance. Mediterranean and polyphenol-rich diets are among the dietary therapies that show promise in modifying the composition of microorganisms, lowering pro-inflammatory signaling, and enhancing neuroprotection. Through microbiota regulation, pharmacological substances such as curcumin, resveratrol, and SCFA mimetics also have anti-neuroinflammatory benefits. However, a number of translational challenges still exist, including limitations in animal models, a lack of standardized therapies, and inter-individual microbiome heterogeneity. In order to provide precise, GBA-targeted therapies, future views place a strong emphasis on integrating multi-omics, artificial intelligence, and personalized medicine. This study highlights a new therapeutic approach to treating neurodegeneration by examining the translational potential of anti- inflammatory therapies targeting GBA. It also emphasizes the necessity of strong clinical studies to confirm these findings.</p>","PeriodicalId":93930,"journal":{"name":"Central nervous system agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147944217","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Therapeutic Insights into Natural Products for Modulating Neurodegenerative Disease Pathways.","authors":"Anjali Sharma, Vishnu Mittal, Devkant Sharma, Geeta Deswal, Amiya Das, Kumar Guarve, Ajmer Singh Grewal","doi":"10.2174/0118715249405308251210104405","DOIUrl":"https://doi.org/10.2174/0118715249405308251210104405","url":null,"abstract":"<p><strong>Introduction: </strong>Neurodegenerative Disorders (NDs), such as Alzheimer's disease, Parkinson's disease, Huntington's disease, and Amyotrophic Lateral Sclerosis (ALS), are chronic and progressive conditions marked by the gradual loss of neuronal structure and function. These disorders lead to cognitive, motor, and sensory decline, significantly reducing quality of life and posing a major global health burden due to rising healthcare costs and the absence of curative therapies. This review aims to comprehensively explore the therapeutic potential of natural products in targeting cellular and molecular mechanisms underlying NDs, highlighting their neuroprotective roles and potential for disease modification.</p><p><strong>Methods: </strong>A comprehensive literature review was conducted using databases including PubMed, Scopus, Web of Science, and Google Scholar. Peer-reviewed articles, clinical trials, and experimental studies were analyzed to evaluate the therapeutic potential of natural products and their bioactive compounds in the management of NDs.</p><p><strong>Results: </strong>ND pathogenesis involves oxidative stress, neuroinflammation, mitochondrial dysfunction, and abnormal protein aggregation, ultimately leading to neuronal death. Current therapies largely provide symptomatic relief without altering disease progression. Natural products from plants, fungi, and marine sources demonstrate strong neuroprotective potential through multitargeted mechanisms. Bioactive compounds such as flavonoids, alkaloids, terpenoids, and polyphenols exhibit antioxidant, anti-inflammatory, anti-apoptotic, and neuroprotective activities. Key molecules, including curcumin, resveratrol, luteolin, quercetin, and catechins, modulate signaling pathways such as NF-κB, MAPK, PI3K/AKT, Nrf2, apoptosis, and autophagy, thereby reducing amyloid-beta aggregation, protecting dopaminergic neurons, improving mitochondrial function, and enhancing cognition in preclinical and clinical studies.</p><p><strong>Discussion: </strong>Natural products represent promising candidates for disease modification in NDs due to their multi-pathway actions and relatively low toxicity. However, major limitations, such as poor bioavailability, pharmacokinetic variability, and the lack of standardized formulations, hinder clinical translation. Innovative strategies, including advanced drug-delivery systems, structural modifications, and synergistic formulations, are needed to overcome these barriers.</p><p><strong>Conclusion: </strong>Natural products hold significant therapeutic potential in managing neurodegenerative diseases by targeting multiple pathological mechanisms. Their integration into ND treatment could provide safer and more effective alternatives, but further well-designed clinical trials are essential to establish their efficacy and facilitate clinical application.</p>","PeriodicalId":93930,"journal":{"name":"Central nervous system agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147944132","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Systematic Review on Isoquinoline Derivatives as Emerging Multi-target Agents in Alzheimer's and Parkinson's Disorder Therapy.","authors":"Indrakumar Subramanian, Remya Ramachandran Surajambika, Dibenthiran Sekar, Ramalakshmi Natarajan, Nalini Calamur Nagarajan","doi":"10.2174/0118715249401454260108062419","DOIUrl":"https://doi.org/10.2174/0118715249401454260108062419","url":null,"abstract":"<p><strong>Introduction: </strong>Neurodegenerative disorders, including Alzheimer's, Parkinson's, multiple sclerosis, amyotrophic lateral sclerosis, and Huntington's disease, are characterized by progressive neuronal loss driven by damage or apoptosis. Although their precise etiologies remain unclear, neuronal degeneration is a common pathological hallmark.</p><p><strong>Methods: </strong>This review compiles and critically evaluates studies investigating the potential of isoquinoline derivatives to mitigate neurodegeneration. Particular attention is given to their inhibitory effects on key enzymes implicated in these disorders and structural modifications aimed at improving potency and reducing toxicity.</p><p><strong>Results: </strong>Experimental findings demonstrate that isoquinoline derivatives exhibit significant inhibitory activity against several neurodegeneration-related enzymes. These compounds show promise in attenuating disease progression in preclinical models, supporting their potential as therapeutic leads.</p><p><strong>Discussion: </strong>Isoquinoline derivatives display multitarget properties, and structural optimization has enhanced their efficacy and safety profiles. Their multifunctional nature could offer advantages over current single-target therapies by improving efficacy and reducing adverse effects.</p><p><strong>Conclusion: </strong>Isoquinoline derivatives represent promising scaffolds for developing novel therapeutics targeting neurodegenerative disorders. However, most data are limited to in vitro and earlystage preclinical studies. Comprehensive mechanistic investigations, standardized in vivo evaluations, and early-phase clinical trials are required to establish their pharmacokinetics, blood-brain barrier permeability, safety, and therapeutic potential.</p>","PeriodicalId":93930,"journal":{"name":"Central nervous system agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147629023","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hydrogel-forming Microneedles: A Next-generation Approach for Enhanced Dermal Drug Delivery in Alzheimer's and Neurological Disorders.","authors":"Jayaramakani Natarajan, Srinivasan Ranganathan","doi":"10.2174/0118715249400208251205125114","DOIUrl":"https://doi.org/10.2174/0118715249400208251205125114","url":null,"abstract":"<p><p>Hydrogel-Forming Microneedles (HFMNs) offer a minimally invasive, patient-friendly, and sustained-release platform for transdermal delivery. By swelling upon insertion to form a hydrogel matrix, they enable efficient delivery of small molecules, biologics, and nanoparticles while bypassing gastrointestinal degradation and first-pass metabolism. In neurological disorders such as Alzheimer's and Parkinson's disease, they can improve bioavailability and overcome Blood-Brain Barrier (BBB) restrictions. However, limitations remain, including limited macromolecule payload, variable skin penetration, and regulatory challenges. To critically review recent progress in HFMNs for neurological drug delivery and assess their translational readiness. The objective is to evaluate advances in design, materials, fabrication, and therapeutic applications, and identify key challenges and future prospects. A literature review (2018-2024) covering polymer selection, crosslinking strategies, smart-material integration, and CNS-targeted applications. HFMNs successfully deliver donepezil, memantine, rivastigmine, and neurotrophic factors, achieving sustained release, improved bioavailability, and enhanced patient compliance. Smart HFMNs with biosensors and nanocarriers show improved BBB penetration. HFMNs represent a promising alternative to conventional CNS drug delivery. Addressing payload, penetration consistency, and scalable manufacturing will be vital for clinical adoption.</p>","PeriodicalId":93930,"journal":{"name":"Central nervous system agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147629262","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ferulic Acid- and Quercetin-based Extracts Enhanced Neuropharmacological Potential in Swiss Albino Mice: Molecular Dynamics Simulation,mMolecular Docking, ADMET, and Biological Investigation.","authors":"Bhawna Shridhar, Jatin Kishore Sharma, Akhlesh Kumari, Sushil Kumar","doi":"10.2174/0118715249404100251204202012","DOIUrl":"https://doi.org/10.2174/0118715249404100251204202012","url":null,"abstract":"<p><strong>Introduction: </strong>Neurological disorders impair cognitive, emotional, and behavioural functions, leading to a reduced quality of life. Due to the limitations of conventional therapies, the present study aimed to develop and evaluate a polyherbal formulation containing Foeniculum vulgare, Emblica officinalis, and Ocimum sanctum for its neuroprotective and anxiolytic potential.</p><p><strong>Methods: </strong>A hydroalcoholic extract of the selected plants was combined in a 3:1:3 ratio to prepare a polyherbal formulation. Phytochemical analysis using Thin Layer Chromatography (TLC) and High-Performance Thin-Layer Chromatography (HPTLC) confirmed the presence of ferulic acid and quercetin as major constituents. Computational approaches, including molecular docking and molecular dynamics simulations, were employed to evaluate the interaction of these compounds with GABA receptors. ADME profiling was conducted to assess pharmacokinetic suitability, and in vivo studies on Swiss albino mice were performed to determine anxiolytic and antistress activities, along with acute toxicity evaluation.</p><p><strong>Results: </strong>The formulation showed strong binding affinity of ferulic acid and quercetin to GABA receptor sites, comparable to diazepam. ADME analysis revealed favourable pharmacokinetic and drug-likeness properties. In vivo behavioural studies demonstrated significant anxiolytic and antistress effects (p < 0.05) without any observable signs of acute toxicity.</p><p><strong>Discussion: </strong>The results indicate that the synergistic interaction of bioactive compounds enhances GABAergic modulation, contributing to the observed neuroprotective and anxiolytic effects. These findings align with previous reports on the neuroactive potential of flavonoid-rich herbal extracts, supporting the therapeutic relevance of polyherbal formulations in neuropharmacology.</p><p><strong>Conclusion: </strong>The developed polyherbal formulation demonstrated promising neuroprotective, anxiolytic, and antistress effects through GABAergic modulation, supported by both computational and experimental evidence. It may serve as a safe, natural, and effective alternative for managing neurological disorders.</p>","PeriodicalId":93930,"journal":{"name":"Central nervous system agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147629277","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neuroprotective Role of Exercise-based Physiotherapy Combined with Pharmacological Agents in Parkinson's Disease.","authors":"Divya Aggarwal, Nitesh Malhotra, Pooja Sharma, Dheeraj Kumar, Shweta Sharma, Parul Sharma","doi":"10.2174/0118715249387823251204095511","DOIUrl":"https://doi.org/10.2174/0118715249387823251204095511","url":null,"abstract":"<p><strong>Introduction: </strong>The progressive neurodegenerative disease known as Parkinson's Disease (PD) is represented by deficits in both motor and non-motor functions. Levodopa and dopamine agonists are examples of pharmaceutical treatments that mainly reduce symptoms without having any discernible neuroprotective effects. The potential of exercise-based physical therapy to improve neuroplasticity and slow disease progression has drawn increasing attention. To provide awareness of their complementary roles in enhancing outcomes for people with PD, this narrative review examines the combined neuroprotective effects of pharmaceutical medicines and physical therapy. The aim of the review was to evaluate the effects of both physical and pharmaceutical therapies in the management of Parkinson's disease to enhance motor recovery and retard disease progression.</p><p><strong>Methods: </strong>The evidence from previous research is compiled in this review, which focuses on preclinical and clinical trials examining the neuroprotective benefits of medication and exercise-based physical therapy. We searched databases such as PubMed, Scopus, Embase, the Cochrane Library, and Web of Science to identify relevant peer-reviewed articles. The review discusses therapeutic synergies, underlying mechanisms, and how these affect clinical practice.</p><p><strong>Results: </strong>Aerobic, resistance, and balance training are examples of exercise-based physiotherapy that reduce oxidative stress, increase brain-derived neurotrophic factor (BDNF) levels, and promote neuroplasticity. These effects enhance the ability of pharmacological drugs to relieve symptoms. Research indicates that, compared to stand-alone treatments, combined therapies produce superior outcomes in motor function, non-motor symptom management, and overall quality of life. The review also highlights important mechanisms of interaction between various medicines, including neuroprotective signaling pathways and improved dopamine utilization.</p><p><strong>Discussion: </strong>Combined therapy in Parkinson's disease enhances neuroprotection by boosting BDNF and other neurotrophic factors, reducing oxidative stress and inflammation, and promoting neurogenesis. Exercise and medications work synergistically to improve neuronal survival, cognition, and motor function. However, challenges include poor patient adherence, limited access to structured programs, limited clinical integration, and the need to tailor treatment to disease stage.</p><p><strong>Conclusion: </strong>A possible method for improving neuroprotection in PD is the combination of pharmaceutical therapies and exercise-based physical therapy. Further research is needed to optimize therapy regimens and develop individualized approaches to enhance patient outcomes and slow disease progression. This combined method offers a multifaceted and comprehensive approach to managing Parkinson's disease.</p>","PeriodicalId":93930,"journal":{"name":"Central nervous system agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147629425","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Emerging Therapies and Research in Alzheimer's Disease: A Critical Review.","authors":"Madan Mohan Agrawal, Payal Mittal","doi":"10.2174/0118715249403872251208145159","DOIUrl":"https://doi.org/10.2174/0118715249403872251208145159","url":null,"abstract":"<p><p>Alzheimer's disease, an extremely prevalent neurological illness and the leading cause of dementia globally, is an extremely prevalent neurological illness and is the leading cause of dementia globally. There are a few treatment options for AD, and those that do exist only slightly reduce symptoms, even after several clinical studies. The formation of Aβ plaques, neuroinflammation, and hyperphosphorylated tau neurofibrillary tangles are the characteristics of AD. While monoclonal antibodies such as lecanemab, donanemab, and aducanumab have demonstrated potential in addressing Aβ, their clinical efficacy and safety over an extended period of time remain uncertain. Novel avenues for tackling the underlying genetic causes of AD have been made possible by developments in genome editing tools, most notably CRISPR-Cas9. In preclinical animals, CRISPR-Cas9 has effectively edited genes relevant to AD, such as APP and PSEN1, leading to decreased levels of Aβ and enhanced cognitive function. Additionally, base and prime editing, two precision gene-editing techniques, have increased the medicines' selectivity and decreased their offtarget effects. However, before clinical applications are deployed, challenges related to technology, ethics, and safety must be resolved. This review highlights how monoclonal antibodies, neuroinflammation research, and CRISPR-Cas9 have the potential to revolutionize therapy choices for AD by examining the most current developments in the field.</p>","PeriodicalId":93930,"journal":{"name":"Central nervous system agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147629274","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical Effects of Recently Developed Antipsychotic Drugs in Schizophrenia.","authors":"Felix-Martin Werner, Rafael Coveñas","doi":"10.2174/0118715249384914251122074130","DOIUrl":"https://doi.org/10.2174/0118715249384914251122074130","url":null,"abstract":"<p><strong>Introduction: </strong>Schizophrenia and schizoaffective disorder are generally treated with second- generation antipsychotic drugs. These drugs are mostly dopaminergic (D2) and serotonergic (5-HT2A) antagonists. They sufficiently improve positive schizophrenia symptoms; however, they ameliorate negative symptoms and cognitive functions only to a limited extent.</p><p><strong>Material and methods: </strong>We review novel antipsychotic drugs that exert partial agonism at dopaminergic and serotonergic receptors, such as cariprazine, brexpiprazole, and lumateperone. In addition, the mechanisms of action of non-dopaminergic antipsychotic drugs are described. Updated neural network models are used to explain the mechanisms of action of muscarinic (M4 and M1) receptor agonists (e.g., xanomeline combined with trospium) and trace-amine-associated receptor 1 (TAAR1) agonists (e.g., ulotaront). Phase 3 clinical trials of new third-generation antipsychotic drugs are also presented.</p><p><strong>Results: </strong>Novel antipsychotic drugs with partial agonism at D2 and D3 receptors improve positive and negative schizophrenia symptoms, as well as cognitive symptoms, more effectively than second- generation antipsychotic drugs. They are also well tolerated. M4 and M1 receptor agonists (i.e., xanomeline combined with trospium or emraclidine) and TAAR1 agonists (i.e., ulotaront) substantially improve negative schizophrenia symptoms and cognitive functions. These new nondopaminergic antipsychotic drugs better ameliorate negative symptoms and improve cognitive functions compared with second-generation antipsychotic drugs.</p><p><strong>Discussion: </strong>Results from phase 3 clinical studies indicate the clinical efficacy of new thirdgeneration antipsychotic drugs.</p><p><strong>Conclusion: </strong>Promising new antipsychotic drugs include cariprazine, brexpiprazole, lumateperone, ulotaront, and xanomeline combined with trospium. Phase 3 clinical studies have shown therapeutic effects superior to those achieved with second-generation antipsychotic drugs.</p>","PeriodicalId":93930,"journal":{"name":"Central nervous system agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146055285","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"New Drug Therapies Against Targeting Neurodegenerative Diseases: A Comprehensive Review.","authors":"Karen Alejandra González-Jiménez, Elsa Verónica Herrera-Mayorga, Francisco Alejandro Paredes Sánchez, Nohemí Niño-García, Jorge Ariel Torres-Castillo, Hadassa Yuef Martínez-Padrón, Mario Sánchez-Sánchez","doi":"10.2174/0118715249397580251117044621","DOIUrl":"https://doi.org/10.2174/0118715249397580251117044621","url":null,"abstract":"<p><p>Neurodegenerative diseases encompass well-characterized behavioral, cognitive, and movement disorders that affect older people, impacting all facets of daily life. In Alzheimer's disease, specific antibodies targeting the β-amyloid protein (aducanumab, lecanemab, and others) are gaining special interest due to the approval of the first particular drugs against this disease. In Parkinson's disease, most drugs were approved several decades ago; however, new Phase II clinical trials point to monoclonal antibodies as a promising approach, and the report of alkaloids also suggests various therapeutic targets against this disease. Pick's disease has a low prevalence; currently, no drugs are approved by government agencies. However, thanks to molecular tools, it has been possible to elucidate therapeutic targets implicated in the appearance of the disease. α-synuclein is the main therapeutic target in Lewy body disease; most of the reported molecules are in clinical Phases I and II. Additionally, drug repositioning may emerge as a viable option in the search for effective treatments against this disease. In amyotrophic lateral sclerosis, the appearance of newly approved drugs such as tofersen and edaravone, and some others in clinical Phase II (bosutinib), opens a new era in the understanding and treatment of this condition. Altered emotions and progressive damage in some brain regions characterize schizophrenia and vascular dementia. Combinations of tricyclic drugs are a trend that aims to increase the cognitive performance of patients with schizophrenia. In vascular dementia, numerous in vivo trials with molecules of different natures (flavonoids and lactones) have yielded positive results, delaying the progression of the disease. This review examines recent reports on molecules evaluated in vivo and in vitro models of the primary neurodegenerative diseases.</p>","PeriodicalId":93930,"journal":{"name":"Central nervous system agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145936652","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}