Central nervous system agents in medicinal chemistry最新文献

{"title":"Evaluation of Safety and Efficacy of Cuprum metallicum in Zebrafish and Mouse Models as a Potential Drug Candidate for the Management of Seizures.","authors":"Mahima Sharma, Vara Prasad Saka, Godlaveti Vijay Narasimha Kumar, Sangita Behera, Rajkumar Regar, Pankaj Gupta, Ritika H Narula","doi":"10.2174/0118715249345785250114222749","DOIUrl":"https://doi.org/10.2174/0118715249345785250114222749","url":null,"abstract":"<p><strong>Background: </strong>In an alternative medicinal system, Cuprum metallicum (CM) is used for the management of seizure-like conditions. However, there is a lack of scientific evidence regarding its effect.</p><p><strong>Objective: </strong>The present study aimed to evaluate the effect of CM against Pentylenetetrazoleinduced seizures in zebrafish and mice.</p><p><strong>Methods: </strong>Zebrafish were exposed to CM-6C, CM-30C, and valproic acid for 1 Hr then fish were exposed to pentylenetetrazole to record seizure score and locomotor pattern using ANY maze video tracking software. Mice were pretreated with CM-6C, CM-30C, and valproic acid for 10 days. After 30 min of the last dose, pentylenetetrazole was administered intraperitoneally. Observations during the next 30 min were recorded to detect latency to first myoclonic jerk (FMJ), tonic-clonic seizures, and the severity of seizure and survival protection after 24 Hrs.</p><p><strong>Results: </strong>PTZ exposure significantly decreased the latency from score-1 to score-5, which CM-6C and 30C significantly increased. Furthermore, CM-6C and 30C normalized the locomotor activity affected by PTZ exposure. Among the animals treated with the CM-6C and 30C, significantly increased latency to FMJ, tonic-clonic seizures, and survival protection compared to the PTZ group of Cuprum met.</p><p><strong>Conclusion: </strong>The results of the study indicate that CM 6C and 30C have the potential to work against seizures as they attenuated the PTZ-induced seizures in Zebrafish and BALB/c mice. It could be presumed that CM-6C and 30C could be a beneficial alternative drug candidate for the treatment of epilepsy.</p>","PeriodicalId":93930,"journal":{"name":"Central nervous system agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143400957","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":"Dimethyl Fumarate Attenuates Behavioral and Structural Impairments Associated with Brain Ischemia in Rats.","authors":"Mohammad Bakhtiari, Masoumeh Emamghoreishi, Maryam Khastkhodaei Ardakani, Mohammad Reza Namavar","doi":"10.2174/0118715249345683250116080547","DOIUrl":"https://doi.org/10.2174/0118715249345683250116080547","url":null,"abstract":"<p><strong>Introduction: </strong>Ischemic stroke remains one of the leading causes of death and physical and mental disability. Oxidative stress, free radicals, and inflammation play critical roles in ischemic brain damage. Free radical scavengers such as edaravone and dimethyl fumarate (DMF), known for their antioxidant and anti-inflammatory properties, are considered promising targets for ischemic stroke treatment. This study aimed to assess the impact of these drugs on brain ischemia.</p><p><strong>Methods: </strong>Forty-nine rats were randomly divided into seven groups: sham, edaravone, and DMF controls, as well as edaravone, DMF 5, 15, and 30 groups. Middle cerebral artery occlusion (MCAO) was induced in all groups except the sham group. The MCAO groups were administered with either the vehicle, edaravone (3 mg/kg), or DMF at doses of 5, 15, and 30 mg/kg twice daily for 14 days. Neurobehavioral assessments were conducted throughout the experiment, and anatomical changes in the brain were evaluated using stereological methods.</p><p><strong>Results: </strong>Edaravone and three doses of DMF improved neurobehavioral functions. All treated rats showed a reduction in the ischemic volume and cell loss in the brain regions when compared with the control animals. MCAO reduced the total number of neurons and just DMF doses had a significant effect on this factor. Interestingly, MCAO increased the number of non-neurons and only the DMF 30 group significantly decreased this parameter. DMF 30 was more effective in ischemic stroke.</p><p><strong>Conclusions: </strong>Although edaravone improved neurological functions and reduced the size of brain ischemia and cell loss, DMF, especially at higher doses, exerted a more beneficial effect on these parameters. Therefore, DMF could be proposed as a reinforcement to currently conventional therapies.</p>","PeriodicalId":93930,"journal":{"name":"Central nervous system agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143124227","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":"Unraveling the Plausible Role of Potassium Channel Openers in Alzheimer's Disease.","authors":"Sarvesh Kumar, Bhupesh Sharma, Anjana Sharma, Nitin Sharma","doi":"10.2174/0118715249330827240819040302","DOIUrl":"10.2174/0118715249330827240819040302","url":null,"abstract":"","PeriodicalId":93930,"journal":{"name":"Central nervous system agents in medicinal chemistry","volume":" ","pages":"87-90"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142006105","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":"Research on Alzheimer's Disease (AD) Involving the Use of <i>In vivo</i> and <i>In vitro</i> Models and Mechanisms.","authors":"Sweta Sinha, Pranay Wal, Prakash Goudanavar, Surisetti Divya, Vishwadeepak Kimothi, Divya Jyothi, Mukesh Chandra Sharma, Ankita Wal","doi":"10.2174/0118715249293642240522054929","DOIUrl":"10.2174/0118715249293642240522054929","url":null,"abstract":"<p><strong>Background: </strong>Alzheimer's Disease (AD) is a neurodegenerative disorder characterized by the progressive formation of extracellular amyloid plaques, intracellular neurofibrillary tangles, inflammation, and impaired antioxidant systems. Early detection and intervention are vital for managing AD effectively.</p><p><strong>Objectives: </strong>This review scrutinizes both <i>in-vivo</i> and <i>in-vitro</i> screening models employed in Alzheimer's disease research. <i>in-vivo</i> models, including transgenic mice expressing AD-related mutations, offer profound insights into disease progression and potential therapeutic targets. A thorough understanding of these models and mechanisms will facilitate the development of novel therapies and interventions for Alzheimer's disease. This review aims to provide an overview of the current experimental models in AD research, assess their strengths and weaknesses as model systems, and underscore the future prospects of experimental AD modeling.</p><p><strong>Methods: </strong>We conducted a systematic literature search across multiple databases, such as Pub- Med, Bentham Science, Elsevier, Springer Nature, Wiley, and Research Gate. The search strategy incorporated pertinent keywords related to Alzheimer's disease, <i>in-vivo</i> models, <i>in-vitro</i> models, and screening mechanisms. Inclusion criteria were established to identify studies focused on <i>in-vivo</i> and <i>in-vitro</i> screening models and their mechanisms in Alzheimer's disease research. Studies not meeting the predefined criteria were excluded from the review.</p><p><strong>Results: </strong>A well-structured experimental animal model can yield significant insights into the neurobiology of AD, enhancing our comprehension of its pathogenesis and the potential for cutting-edge therapeutic strategies. Given the limited efficacy of current AD medications, there is a pressing need for the development of experimental models that can mimic the disease, particularly in pre-symptomatic stages, to investigate prevention and treatment approaches. To address this requirement, numerous experimental models replicating human AD pathology have been established, serving as invaluable tools for assessing potential treatments.</p><p><strong>Conclusion: </strong>In summary, this comprehensive review underscores the pivotal role of <i>in-vivo</i> and <i>in-vitro</i> screening models in advancing our understanding of Alzheimer's disease. These models offer invaluable insights into disease progression, pathological mechanisms, and potential therapeutic targets. By conducting a rigorous investigation and evaluation of these models and mechanisms, effective screening and treatment methods for Alzheimer's disease can be devised. The review also outlines future research directions and areas for enhancing AD screening models.</p>","PeriodicalId":93930,"journal":{"name":"Central nervous system agents in medicinal chemistry","volume":" ","pages":"123-142"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141158863","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":"Beta-site APP-cleaving Enzyme-1 Inhibitory Role of Natural Flavonoids in the Treatment of Alzheimer's Disease.","authors":"Sandeep Singh, Virendra Kushwaha, Shriram Sisodia, Shivendra Kumar, Kantrol Kumar Sahu","doi":"10.2174/0118715249315049240710063455","DOIUrl":"10.2174/0118715249315049240710063455","url":null,"abstract":"<p><p>Alzheimer's Disease (AD) is a devastating neurological condition characterized by a progressive decline in cognitive function, including memory loss, reasoning difficulties, and disorientation. Its hallmark features include the formation of neurofibrillary tangles and neuritic plaques in the brain, disrupting normal neuronal function. Neurofibrillary tangles, composed of phosphorylated tau protein and neuritic plaques, containing amyloid-β protein (Aβ) aggregates, contribute to the degenerative process. The discovery of the beta-site amyloid precursor protein cleaving enzyme 1 (BACE1) in 1999 revolutionized our understanding of AD pathogenesis. BACE1 plays a crucial role in the production of Aβ, the toxic protein implicated in AD progression. Elevated levels of BACE1 have been observed in AD brains and bodily fluids, underscoring its significance in disease onset and progression. Despite setbacks in clinical trials of BACE1 inhibitors due to efficacy and safety concerns, targeting BACE1 remains a promising therapeutic strategy for early-stage AD. Natural flavonoids have emerged as potential BACE1 inhibitors, demonstrating the ability to reduce Aβ production in neuronal cells and inhibit BACE1 activity. In our review, we delve into the pathophysiology of AD, highlighting the central role of BACE1 in Aβ production and disease progression. We explore the therapeutic potential of BACE1 inhibitors, including natural flavonoids, in controlling AD symptoms. Additionally, we provide insights into ongoing clinical trials and available patents in this field, shedding light on future directions for AD treatment research.</p>","PeriodicalId":93930,"journal":{"name":"Central nervous system agents in medicinal chemistry","volume":" ","pages":"39-48"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141617812","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":"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}