Central nervous system agents in medicinal chemistry最新文献

{"title":"Redirecting Research to Alzheimer's Disease.","authors":"Ramón Cacabelos","doi":"10.2174/187152492501241014100836","DOIUrl":"https://doi.org/10.2174/187152492501241014100836","url":null,"abstract":"","PeriodicalId":93930,"journal":{"name":"Central nervous system agents in medicinal chemistry","volume":"25 1","pages":"1-2"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143070237","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":"The Role of Nanotechnology in Understanding the Pathophysiology of Traumatic Brain Injury.","authors":"Saranya Selvaraj, Laksiri Weerasinghe","doi":"10.2174/0118715249291999240418112531","DOIUrl":"10.2174/0118715249291999240418112531","url":null,"abstract":"<p><p>Recently, traumatic brain injury (TBI) has been a growing disorder due to frequent brain dysfunction. The Glasgow Coma Scale expresses TBI as classified as having mild, moderate, or severe brain effects, according to the effects on the brain. Brain receptors undergo various modifications in their pathology through chemical synaptic pathways, leading to depression, Alzheimer's, and Parkinson's disease. These brain disorders can be controlled using central receptors such as dopamine, glutamate, and γ-aminobutyric acid, which are clearly explained in this review. Furthermore, there are many complications in TBI's clinical trials and diagnostics, leading to insignificant treatment, causing permanent neuro-damage, physical disability, and even death. Bio-screening and conventional molecular-based therapies are inappropriate due to poor preclinical testing and delayed recovery. Hence, modern nanotechnology utilizing nanopulsed laser therapy and advanced nanoparticle insertion will be suitable for TBI's diagnostics and treatment. In recent days, nanotechnology has an important role in TBI control and provides a higher success rate than conventional therapies. This review highlights the pathophysiology of TBI by comprising the drawbacks of conventional techniques and supports suitable modern alternates for treating TBI.</p>","PeriodicalId":93930,"journal":{"name":"Central nervous system agents in medicinal chemistry","volume":" ","pages":"20-38"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140861919","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":"Safeguarding Neuronal Integrity: Unveiling Possible Role of NFκB in the Neuroprotective Efficacy of Andrographolide Contrary to Aluminium Chloride-induced Neurotoxicity and Associated Spatial Memory Impairments in Rats.","authors":"Abhitinder Kumar, Mohit Agrawal, Yogesh Murti, Simran Behl, Shivendra Kumar, Hema Chaudhary, Kuldeep Singh, Sunam Saha, Sameer Rastogi","doi":"10.2174/0118715249284798240509052913","DOIUrl":"10.2174/0118715249284798240509052913","url":null,"abstract":"<p><strong>Objective: </strong>The current study was structured to evaluate the neuroprotective properties of andrographolide in the context of aluminum chloride (AlCl<i>3</i>)-induced neurotoxicity, along with its concurrent impact on spatial memory impairment in Wistar rats. The present investigation elucidated the biochemical and neurobehavioral outcomes of andrographolide treatment in rats, emphasizing the areas of the brain associated with memory, i.e., the cortex and the hippocampus.</p><p><strong>Materials and methods: </strong>Prolonged dosing of AlC<i>l3</i>(7 mg/kg) intraperitoneally for 10 days exhibited a substantial enhancement in the values of oxidative stress markers associated with a reduction in the concentrations of antioxidant enzymes within the brain. The selection of andrographolide doses (1, 2, and 3 mg/kg) was grounded in precedent safety and toxicity investigations, with subsequent oral administration. The evaluation of behavioral parameters, specifically spatial memory, was conducted through the utilization of the Radial Eight Arm Maze (RAM) test. On the concluding day of the experiment, the assessment encompassed biochemical parameter analysis and histological scrutiny of the brain tissue.</p><p><strong>Results: </strong>The oral dosing of andrographolide at 1, 2, and 3 mg/kg, in conjunction with AlCl<i>l3</i> effectively mitigated the behavioral deficits induced by aluminum exposure. Notably, a significant suppression of NFκB was uncovered in the rats treated with andrographolide. Furthermore, histopathological examinations of the cortex and hippocampus of rat brains provided corroborative evidence, demonstrating that andrographolide substantially alleviated the toxic impact of AlCl<i>l3</i>, thereby maintaining the typical histoarchitectural arrangement of these regions.</p><p><strong>Conclusion: </strong>These findings collectively suggest that andrographolide holds the potential to counteract memory impairment instigated by aluminum toxicity, accomplished through the modulation of NFκB activity and the amelioration of the adverse consequences of AlCl<i>l3</i> exposure.</p>","PeriodicalId":93930,"journal":{"name":"Central nervous system agents in medicinal chemistry","volume":" ","pages":"157-168"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141082873","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 Review of the Association between Infections, Seizures, and Drugs.","authors":"Zahra Tolou-Ghamari","doi":"10.2174/0118715249288932240416071636","DOIUrl":"10.2174/0118715249288932240416071636","url":null,"abstract":"<p><strong>Background: </strong>Seizures are a common presenting symptom of the central nervous system (CNS) and could occur from infections (such as toxins) or drugs.</p><p><strong>Objective: </strong>The aim of this study was to present a systematic review of the association between infections, seizures, and drugs.</p><p><strong>Methods: </strong>From their inception to 18 February 2024 relevant in-depth consequent guide approach and the evidence-based choice were selected associated with a knowledgeable collection of current, high-quality manuscripts.</p><p><strong>Results: </strong>Imbalance between inhibitory and excitatory neurotransmitters due to infections, drugs such as ticarcillin, amoxicillin, oxacillin, penicillin G, ampicillin, tramadol, venlafaxine, cyclosporine, tacrolimus, acyclovir, cellcept, the old generation of antiepileptic drugs, such as carbamazepine, phenytoin, and many other drugs could cause different stages of CNS disturbances ranging from seizure to encephalopathy. Infections could cause life-threatening status epilepticus by continuous unremitting seizures lasting longer than 5 minutes or recurrent seizures. Meningitis, tuberculosis, herpes simplex, cerebral toxoplasmosis, and many others could lead to status epilepticus. In fact, confusion, encephalopathy, and myoclonus were reported with drugs, such as ticarcillin, amoxicillin, oxacillin, penicillin G, ampicillin, and others. Penicillin G was reported as having the greatest epileptogenic potential. A high dose, in addition to prolonged use of metronidazole, was reported with seizure infection. Meropenem could decrease the concentration of valproic acid. Due to the inhibition of cytochrome P450 3A4, the combination of clarithromycin and erythromycin with carbamazepine needs vigilant monitoring.</p><p><strong>Conclusion: </strong>Due to changes in drug metabolism, co-administration of antiseizure drugs and antibiotics may lead to an enhanced risk of seizures. In patients with neurocysticercosis, cerebral malaria, viral encephalitis, bacterial meningitis, tuberculosis, and human immunodeficiency virus, the evidence-based study recommended different mechanisms mediating epileptogenic properties of toxins and drugs.</p>","PeriodicalId":93930,"journal":{"name":"Central nervous system agents in medicinal chemistry","volume":" ","pages":"49-55"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140862976","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":"Toxicity Concerns Associated with the Radiopharmaceuticals for the Diagnosis of Alzheimer's Disease.","authors":"Shristy Verma, Rishabha Malviya, Sathvik Belagodu Sridhar","doi":"10.2174/0118715249340822240828065449","DOIUrl":"10.2174/0118715249340822240828065449","url":null,"abstract":"","PeriodicalId":93930,"journal":{"name":"Central nervous system agents in medicinal chemistry","volume":" ","pages":"83-86"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142156942","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":"The Effect of Probiotics and Microbiota on Nervous System and Mental Illnesses.","authors":"Hadi Hossainpour, Salman Khazaei, Hassan Mahmoudi","doi":"10.2174/0118715249315760240905043415","DOIUrl":"10.2174/0118715249315760240905043415","url":null,"abstract":"<p><p>The microbiota that inhabits the gastrointestinal tract has been linked to various gastrointestinal and non-gastrointestinal disorders. Scientists have been studying how the bacteria in our intestines have an effect on our brain and nervous system. This connection is called the \"microbiota-gut-brain axis\". Given the capacity of probiotics, which are live non-pathogenic microorganisms, to reinstate the normal microbial population within the host and confer advantages, their potential impact has been subjected to scrutiny with regard to neurological and mental conditions. Material sourced for this review included peer-reviewed literature annotated in the PubMed, Web of Science, Scopus, and Google Scholar databases. The result has indicated the integration of probiotics into a child's diet to enhance the neuro-behavioral symptoms. Notwithstanding this, the current data set has been found to be insufficient and inconclusive. The potential utility of probiotics for the prevention or treatment of neurologic and mental disorders has become a subject of substantial interest.</p>","PeriodicalId":93930,"journal":{"name":"Central nervous system agents in medicinal chemistry","volume":" ","pages":"109-122"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142309363","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 of the Anti-seizure and Antiepileptic Effects and Mechanisms of Piperine.","authors":"Nasim Rahimi-Dehkordi, Saeid Heidari-Soureshjani, Sahar Rostamian","doi":"10.2174/0118715249297934240630111059","DOIUrl":"10.2174/0118715249297934240630111059","url":null,"abstract":"<p><strong>Introduction and aims: </strong>Seizures due to epilepsy in any form cause a wide range of problems in a patient's physical, psychological, and social health. This study aimed to investigate piperine's anti-seizure and antiepileptic effects and mechanisms.</p><p><strong>Methods: </strong>In this systematic review study, which was conducted according to the principles of PRISMA 2020, the initial search was conducted on November 2, 2023, using EndNote software. Various databases such as PubMed, Cochrane Library, Web of Science, Embase, and Scopus were searched using specific keywords. After screening the articles, a form was designed according to the objectives of the study, and the information related to the included articles was entered in the form, and the studies were reviewed.</p><p><strong>Results: </strong>Piperine showed its antiepileptic activity by affecting the brain's antioxidant, anti-inflammatory, and anti-apoptotic activity. It also, by modulating brain-derived neurotrophic factor (BDNF) and gamma-aminobutyric acid (GABA)ergic activity, can control seizures. In addition, piperine can help treat seizures and epilepsy by elevating 5-HT levels in the brain, modulating astrocyte and microglia function, modulatory effects on Ca²⁺ and NA⁺ channels, increasing antiepileptic drugs bioavailability and influencing protein and gene expression.</p><p><strong>Conclusion: </strong><i>In vivo</i> and <i>in vitro</i> studies showed beneficial effects on treating epilepsy. Although clinical studies also showed similar results, these needed to be increased, and more clinical studies needed to be designed in this field.</p>","PeriodicalId":93930,"journal":{"name":"Central nervous system agents in medicinal chemistry","volume":" ","pages":"143-156"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141857393","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":"Investigating the Therapeutic Property of Galium verum L. (GV) for MSG induced Audiogenic Epilepsy (AEs) and Neuroprotection through <i>In-Silico</i> and <i>In-Vitro</i> Analysis.","authors":"Mansi Singh, Siva Prasad Panda","doi":"10.2174/0118715249330123240822063420","DOIUrl":"10.2174/0118715249330123240822063420","url":null,"abstract":"<p><strong>Background: </strong>Audiogenic Epilepsy (AEs) is a subtype of epileptic seizure that is generally caused by high-intensity sounds. A large number of traditional medicines has been explored in this lieu where our study chased <i>Galium verum</i> L. (Rubiaceae), an herbal plant which is commonly known as Lady's Bedstraw, that contains a highly rich chemical composition including flavonoids (Hispidulin, Quercetin, and Kaempferol), and phenolic acids (chlorogenic acid, caftaric acid, and gallic acid). <i>G verum</i> is well known for its antioxidant, neuroprotective, and anti-inflammatory properties. Recently, the unique role of Adhesion G Protein- Coupled Receptor V1 (ADGRV1) protein in the progression of audiogenic epilepsy has been explored.</p><p><strong>Aims and objectives: </strong>This study aimed to examine the potent phytoconstituents of the hydroalcoholic extract of <i>G. verum L.</i> (HEGV) using analytical techniques. Additionally, our study sought to evaluate the antioxidant, neuroprotective, anti-inflammatory properties, and antiepileptic potency of HEGV by targeting ADGRV1 <i>via in silico</i> and <i>in vitro</i> analyses using SHSY5Y cells.</p><p><strong>Methods: </strong>HPLC and LC-MS techniques were employed to identify the flavonoids, iridoids, and phenolic acid derivatives present in HEGV. DPPH (2,2-diphenyl-1-picrylhydrazyl), nitric oxide (NO), and hydroxyl (OH) radical scavenging assays were performed to confirm the antioxidant potential of the extract. Additionally, <i>in silico</i> molecular docking and molecular dynamic studies were performed using AutoDock Vina software to analyze the possible interactions between crucial phytoconstituents of HEGV and ADGRV1, followed by cell line analysis. In the in vitro analysis, antioxidant, neuroprotective, and anti-inflammatory properties were assessed <i>via </i>cell viability assay, IL, GABA, and glutamate estimation.</p><p><strong>Results: </strong>LC-MS and HPLC analyses revealed high concentrations of hispidulin, a major flavonoid found in HEGV. HEGV exhibited moderate-to-high free radical-scavenging activities comparable to those of ascorbic acid. Docking analysis demonstrated that hispidulin has a stronger binding affinity with ADGRV1 (Vina score = -8.6 kcal/mol) than other compounds. Furthermore, cell line analysis revealed that the MSG exacerbates the neurodegeneration and neuroinflammation, whereas, HEGV and Hispidulin both possess neuroprotective, antioxidant, and antiepileptic activities.</p><p><strong>Conclusion: </strong>HEGV and Hispidulin proved to be promising candidates for treating audiogenic epilepsy by modulating ADGRV1.</p>","PeriodicalId":93930,"journal":{"name":"Central nervous system agents in medicinal chemistry","volume":" ","pages":"181-209"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142303392","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":"Targeting Adenylate Cyclase: A Novel Concept for Stimulation of Neurogenesis and Pharmacotherapy of Alzheimer's Disease.","authors":"Gleb Nikolaevich Zyuz'kov, Larisa Arkad Evna Miroshnichenko, Tatyana Yur Evna Polykova, Elena Vladislavovna Simanina, Alexander Vasil Evich Chayikovskyi","doi":"10.2174/0118715249302264240715060630","DOIUrl":"10.2174/0118715249302264240715060630","url":null,"abstract":"<p><strong>Background: </strong>The low effectiveness of existing pharmacotherapy strategies for Alzheimer's disease (AD) makes it necessary to develop a new concept for the treatment of this type of dementia. This search is promising to be carried out within the framework of the paradigm of targeting intracellular signaling pathways in Regenerative-competent Cells (RCCs).</p><p><strong>Objectives: </strong>The purpose of the research is to study the impact of adenylate cyclase (AC) inhibitor on disorders of the psychoemotional status in aged male C57BL/6 mice, as well as on the dynamics of the content and functioning of RCCs nervous tissue.</p><p><strong>Methods: </strong>We examined the effect of the AC inhibitor (2',5'-Dideoxyadenosine) on conditioned reflex activity, behavioral and emotional profile in a mouse AD model (16-month-old (aged) male C57BL/6 mice), as well as the functioning of neural stem cells (NSCs), neuronal-committed progenitors (NCPs), and neuroglial cells in the subventricular zone of the cerebral hemispheres (SVZ).</p><p><strong>Results: </strong>In aged C57BL/6 mice, we found impairments in exploratory behavior, emotional reactivity, and memory, which are the characteristics of senile dementia. Therapy based on AC inhibition led to an increase in the number of NSCs and NPCs in the SVZ due to an increase in their proliferative activity. These changes were more pronounced in NCPs. At the same time, a decrease in the specialization intensity was recorded in NSCs. These phenomena developed against the background of increased secretion of neurotrophic growth factors by oligodendrocytes and microglial cells. The neuroregenerative effects of 2',5'-dideoxyadenosine correlated with the correction of age-related disorders of the psychoemotional status in aged mice.</p><p><strong>Conclusion: </strong>The results provide the basis for the development of targeted drugs based on AC inhibitors to stimulate neurogenesis as an approach for the effective treatment of AD.</p>","PeriodicalId":93930,"journal":{"name":"Central nervous system agents in medicinal chemistry","volume":" ","pages":"169-180"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141794261","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":"Unveiling the Mysteries of the Blood-brain Barrier: The Problem of the Brain/spinal Pharmacotherapy.","authors":"Aditya Walia, Amandeep Kaur, Randhir Singh, Nidhi Rani, Rajan Swami","doi":"10.2174/0118715249297247240813104929","DOIUrl":"10.2174/0118715249297247240813104929","url":null,"abstract":"<p><p>The most critical issue impeding the development of innovative cerebrospinal medications is the blood-brain barrier (BBB). The BBB limits the ability of most medications to penetrate the brain to the CNS. The BBB structure and functions are summarized, with the physical barrier generated by endothelial tight junctions and the transport barrier formed by transporters within the membrane and vesicular processes. The functions of connected cells, particularly the end feet of astrocytic glial cells, microglia, and pericytes, are described. The drugs that cross the blood brain barrier are explained below along with their mechanisms. Some of the associated conditions and problems are given.</p>","PeriodicalId":93930,"journal":{"name":"Central nervous system agents in medicinal chemistry","volume":" ","pages":"91-108"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142115917","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}