Central nervous system agents in medicinal chemistry最新文献

{"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":"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":"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":"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}

{"title":"Nanomedicine: A New Frontier in Alzheimer's Disease Drug Targeting.","authors":"Kalyani Pathak, Mohammad Zaki Ahmad, Riya Saikia, Manash Pratim Pathak, Jon Jyoti Sahariah, Parimita Kalita, Aparoop Das, Md Ariful Islam, Pallab Pramanik, Dubom Tayeng, Basel A Abdel-Wahab","doi":"10.2174/0118715249281331240325042642","DOIUrl":"10.2174/0118715249281331240325042642","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is a prevalent neurodegenerative disorder affecting elderly individuals, characterized by progressive cognitive decline leading to dementia. This review examines the challenges posed by anatomical and biochemical barriers such as the blood-brain barrier (BBB), blood-cerebrospinal fluid barrier (BCSFB), and p-glycoproteins in delivering effective therapeutic agents to the central nervous system (CNS) for AD treatment. This article outlines the fundamental role of acetylcholinesterase inhibitors (AChEIs) and NMDA(N-Methyl-D-Aspartate) receptor antagonists in conventional AD therapy and highlights their limitations in terms of brain-specific delivery. It delves into the intricacies of BBB and pglycoprotein- mediated efflux mechanisms that impede drug transport to the CNS. The review further discusses cutting-edge nanomedicine-based strategies, detailing their composition and mechanisms that enable effective bypassing of BBB and enhancing drug accumulation in brain tissues. Conventional therapies, namely AChEIs and NMDA receptor antagonists, have shown limited efficacy and are hindered by suboptimal brain penetration. The advent of nanotechnology-driven therapeutic delivery systems offers promising strategies to enhance CNS targeting and bioavailability, thereby addressing the shortcomings of conventional treatments. Various nanomedicines, encompassing polymeric and metallic nanoparticles (MNPs), solid lipid nanoparticles (SLNs), liposomes, micelles, dendrimers, nanoemulsions, and carbon nanotubes, have been investigated for their potential in delivering anti-AD agents like AChEIs, polyphenols, curcumin, and resveratrol. These nanocarriers exhibit the ability to traverse the BBB and deliver therapeutic payloads to the brain, thereby holding immense potential for effective AD treatment and early diagnostic approaches. Notably, nanocarriers loaded with AChEIs have shown promising results in preclinical studies, exhibiting improved therapeutic efficacy and sustained release profiles. This review underscores the urgency of innovative drug delivery approaches to overcome barriers in AD therapy. Nanomedicine-based solutions offer a promising avenue for achieving effective CNS targeting, enabling enhanced bioavailability and sustained therapeutic effects. As ongoing research continues to elucidate the complexities of CNS drug delivery, these advancements hold great potential for revolutionizing AD treatment and diagnosis.</p>","PeriodicalId":93930,"journal":{"name":"Central nervous system agents in medicinal chemistry","volume":" ","pages":"3-19"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140320127","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":"Lead Phytomolecules for Treating Parkinson's Disease.","authors":"Krishn Kumar Agrawal, Chandra Veer, Yogesh Murti, Sunil Pratap Singh","doi":"10.2174/0118715249355503241210101001","DOIUrl":"https://doi.org/10.2174/0118715249355503241210101001","url":null,"abstract":"<p><p>One percent of persons over 65 years of age suffer from Parkinson's disease, a neurological ailment marked by dopaminergic neurons in the nigrostriatal pathway gradually dying and being depleted in the striatum. Parkin and PINK1 gene mutations, which are essential for mitophagy and impair mitochondrial function, are the cause of it. Parkinson's disease is linked to a number of motor and impairment disorders, including bradykinesia, rigid muscles, tremor at rest, and imbalance. Numerous signaling pathways, including α-synuclein aggregation, lead to age-related decline in proteolytic defense systems. Parkinson's disease etiology involves oxidative stress, ferroptosis, mitochondrial failure, and neuroinflammation. Parkinson's disease is significantly influenced by neuroinflammation, which is a result of both innate and adaptive immune responses. The purpose of studying mechanisms and phytomolecules is to assist researchers in creating therapies for Parkinson's disease. Phytomolecules, like curcumin, β- amyrin, berberine, capsaicin, and gentisic acid, exert neuroprotective properties by reducing ROS levels, lessening α-synuclein-induced toxicity, and shielding the cells from apoptosis. In conclusion, the studies presented here provide valuable insights into the potential of various medications for Parkinson's disease treatment. By understanding the mechanisms behind these treatments, researchers can develop more effective treatments for PD.</p>","PeriodicalId":93930,"journal":{"name":"Central nervous system agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142857293","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 Importance of Stem Cells in the Treatment of Neuropathic Pain.","authors":"Farshad Hassanzadeh Kiabi, Tayebeh Khosravi, Saeed Gharooee Ahangar, Siavash Beiranvand","doi":"10.2174/0118715249328823241111101137","DOIUrl":"https://doi.org/10.2174/0118715249328823241111101137","url":null,"abstract":"<p><p>Many disorders, including heart, bone, cancer, liver, and brain disease, have been treated using stem cell therapy as a viable alternative. The somatosensory system is affected by a lesion, which leads to neuropathic pain (NP), and just a relatively tiny fraction of patients now receive effective care from existing pharmacological medications. There have been studies to show the effectiveness of various stem cells in reducing or treating experimental neurological pain, although these studies are uncommon in number. In this narrative review, we will summarize the preclinical and clinical research that has been conducted on the effectiveness of several stem cell types, such as mesenchymal stem cells, bone-derived stem cells, and neural stem cells, in reducing neurological pain in this study.</p>","PeriodicalId":93930,"journal":{"name":"Central nervous system agents in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142775448","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}