Current Neuropharmacology最新文献

{"title":"The Modulatory Effects of Anesthetics and Analgesics on Neurophysiological Monitoring and Underlying Mechanisms.","authors":"Yu Leng, Yi Teng, Jin Liu, Xian Zou, Mengchan Ou, Tao Zhu, Peng Liang, Cheng Zhou","doi":"10.2174/011570159X349119250127104107","DOIUrl":"https://doi.org/10.2174/011570159X349119250127104107","url":null,"abstract":"<p><p>Intraoperative Neurophysiological Monitoring (IONM) is an indispensable surgical tool that offers invaluable insights into neurological function across a spectrum of anatomical areas. By comprehensively assessing the integrity of the brain, brainstem, spinal cord, cranial nerves, and peripheral nerves, IONM plays a pivotal role in guiding surgical decision-making and optimizing patient outcomes, particularly in the context of high-risk procedures. Intraoperative drugs, especially anesthetics and/or analgesics, differentially modulate neurophysiological monitoring, which remarkably affects the application of neurophysiological monitoring under specific conditions and indicates the neurobiological mechanisms of anesthetics/analgesics. This review will describe various neurophysiological modalities utilized in intraoperative procedures, each employing a wide variety of physiological principles; summarize the modulatory effects of anesthetics/analgesics on these neurophysiological monitoring parameters; and elucidate their underlying mechanisms, with a particular emphasis on evoked potentials. Insights gleaned from this review can inform strategies of anesthesia management for surgeries that require IONM and guide future investigations on the mechanisms of anesthesia/analgesia.</p>","PeriodicalId":10905,"journal":{"name":"Current Neuropharmacology","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143456658","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of a Rosiridin against Rotenone-induced Rats' Model of Parkinson's Disease: In-vivo Study and in silico Molecular Modeling.","authors":"Misbahuddin Rafeeq, Fahad A Al-Abbasi, Muhammad Afzal, Khalid Saad Alharbi, Ehssan Moglad, Salwa D Al-Qahtani, Hussam A Bukhari, Faisal Imam, Nadeem Sayyed, Imran Kazmi","doi":"10.2174/011570159X349553250126050134","DOIUrl":"https://doi.org/10.2174/011570159X349553250126050134","url":null,"abstract":"<p><strong>Aim: </strong>The investigation aimed to study the outcome of rosiridin in Parkinson's disease (PD) induced by rotenone (ROT) in rodents.</p><p><strong>Methods: </strong>Rodents were randomized into IV groups and were induced with ROT followed by treatment with rosiridin. Group I-IV received saline as a vehicle, II-ROT (0.5 mg/kg S.C) for 28 consecutive days, III and IV- rosiridin 10 and 20 mg/kg orally with ROT. On completion of the experimental duration, behavioral investigations were carried out. Biochemical variables such as acetylcholinesterase (AChE), oxidative stress and antioxidants markers (Malondialdehyde-MDA, glutathione-GSH, superoxide dismutase-SOD, and catalase-CAT), anti-inflammatory (Interleukin-1 beta-IL-1β, IL-6, and tumor necrosis factor alpha-TNF-α), alteration in neurotransmitters (Serotonin-5-HT), norepinephrine, and dopamine-DA, along with metabolites such as 5-hydroxy indole acetic acid-5- HIAA),), mitochondrial complex I, II, IV, and caspase-3 activity were evaluated at the end of the experiment. Furthermore, molecular docking and dynamics were performed for target ligands.</p><p><strong>Results: </strong>Rosiridin significantly restored the level of AChE, oxidative stress and antioxidants markers (MDA, GSH, SOD, and CAT), anti-inflammatory (IL-1β, IL-6, and TNF-α), alteration in neurotransmitters, mitochondrial complex I, II, IV, and caspase-3 activity. Rosiridin has a favorable negative binding affinity to AChE (-8.99 kcal/mol). The results of the molecular dynamics simulations indicate that proteins undergo a substantial change in conformational dynamics when binding to rosiridin.</p><p><strong>Conclusion: </strong>In this study, rosiridin may exhibit neuroprotective properties against the Parkinson's model for treating PD.</p>","PeriodicalId":10905,"journal":{"name":"Current Neuropharmacology","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143413716","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transient Receptor Potential Ankyrin 1 (TRPA1) Mediates Hydrogen Sulfide-induced Ca2+ Entry and Nitric Oxide Production in Human Cerebrovascular Endothelium.","authors":"Teresa Soda, Valentina Brunetti, Giovambattista De Sarro, Gerardo Biella, Francesco Moccia, Roberto Berra-Romani, Giorgia Scarpellino","doi":"10.2174/011570159X349872250124124612","DOIUrl":"https://doi.org/10.2174/011570159X349872250124124612","url":null,"abstract":"<p><strong>Introduction: </strong>The gasotransmitter hydrogen sulfide (H2S) modulates various brain functions, including neuron excitability, synaptic plasticity, and Ca2+ dynamics. Furthermore, H2S may stimulate nitric oxide (NO) release from cerebrovascular endothelial cells, thereby regulating NO-dependent endothelial functions, such as angiogenesis, vasorelaxation, and cerebral blood flow (CBF). However, the signaling pathway by which H2S induces NO release from cerebrovascular endothelial cells is still unclear.</p><p><strong>Methods: </strong>Herein, we exploited single-cell imaging of intracellular Ca2+, H2S, and NO levels to assess how H2S induces Ca2+-dependent NO release from the human cerebrovascular endothelial cell line, hCMEC/D3.</p><p><strong>Results: </strong>Administration of the H2S donor, sodium hydrosulfide (NaHS), induced a dose-dependent increase in (Ca2+)i only in the presence of extracellular Ca2+. NaHS-induced extracellular Ca2+ entry was mediated by the Ca2+-permeable TRPA1 channel, as shown by pharmacological and genetic manipulation of the TRPA1 protein. Furthermore, NaHS-dependent TRPA1 activation led to NO release that was abolished by buffering the concomitant increase in (Ca2+)i and inhibiting eNOS. Furthermore, the endothelial agonist, adenosine trisphosphate (ATP), caused a long-lasting elevation in (Ca2+)i that was driven by cystathionine γ-lyase (CSE)-dependent H2S production and by TRPA1 activation. Consistent with this, ATP-induced NO release was strongly reduced either by blocking CSE or by inhibiting TRPA1.</p><p><strong>Conclusion: </strong>These findings demonstrate for the time that H2S stimulates TRPA1 to induce NO production in human brain microvascular endothelial cells. Additionally, they show that this signaling pathway can be recruited by an endothelial agonist to modulate NO-dependent events at the human neurovascular unit.</p>","PeriodicalId":10905,"journal":{"name":"Current Neuropharmacology","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143413719","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Role of Epigenetics in the Pathogenesis and Potential Treatment of Obsessive-compulsive Disorder.","authors":"Jacob Peedicayil","doi":"10.2174/011570159X347479241024120728","DOIUrl":"https://doi.org/10.2174/011570159X347479241024120728","url":null,"abstract":"<p><p>Obsessive-compulsive disorder is a common neuropsychiatric disorder that markedly affects the quality of life of affected patients. There is increasing evidence that abnormal epigenetic mechanisms of gene expression are involved in the pathogenesis of this disorder. This article reviews the available data on epigenetic abnormalities found in patients with this disorder. The article also reviews the data on the use of epigenetic therapy in the treatment of obsessive-compulsive disorder, and epigenetic changes noted during psychotherapy of patients with this disorder. More detailed knowledge of the role of abnormal epigenetic mechanisms underlying obsessive-compulsive disorder could facilitate the development of new drugs for treating this disorder and the development of biomarkers for this disorder.</p>","PeriodicalId":10905,"journal":{"name":"Current Neuropharmacology","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143406233","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unveiling the Potential Neuroprotective Effect of Bioactive Compounds from Plants with Sedative and Mood-Modulating Properties: Innovative Approaches for the Prevention of Alzheimer's and Parkinson's Diseases.","authors":"Piccirillo Silvia, Alessandra Preziuso, Serfilippi Tiziano, Giorgia Cerqueni, Valentina Terenzi, Vincenzo Lariccia, Simona Magi","doi":"10.2174/011570159X345397241210103538","DOIUrl":"https://doi.org/10.2174/011570159X345397241210103538","url":null,"abstract":"<p><p>Neurodegenerative diseases like Alzheimer's disease and Parkinson's disease are severe disorders characterized by progressive neuron degeneration, leading to cognitive decline, motor dysfunction, and other neurological issues, significantly impairing daily life and the quality of life. Despite advancements in understanding these mechanisms, many aspects remain unclear, and current treatments primarily manage symptoms without halting disease progression. Multiple biological pathways are implicated in neurodegeneration, including oxidative stress, neuroinflammation, mitochondrial dysfunction, and aberrant protein folding. Given the multifactorial nature of neurodegenerative diseases, a neuroprotective approach targeting various mechanisms holds significant promise for prevention. Natural products derived from plants, animals, and fungi, known for their antioxidant and anti-inflammatory properties, show substantial potential in the prevention of neurodegeneration. Unlike synthetic compounds, bioactive compounds from these natural sources offer diverse targets due to their varied structures and biological activities. This review focuses on the potential of bioactive compounds from plants with sedative and mood-modulating effects in preventing and/or slowing down neurodegeneration.</p>","PeriodicalId":10905,"journal":{"name":"Current Neuropharmacology","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143413645","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Vitamin C Protects from Impairment of Memory Induced by E-Cigarette Aerosol Exposure.","authors":"Karem H Alzoubi, Omar F Khabour, Nour Al-Sawalha, Enaam M Al Momany, Anan Jarab, Razan Haddad, Nasr Alrabadi, Mohammad A Y Alqudah, Toka K Al-Zoubi, Thomas Eissenberg","doi":"10.2174/011570159X341759250119141806","DOIUrl":"https://doi.org/10.2174/011570159X341759250119141806","url":null,"abstract":"<p><strong>Introduction: </strong>E-cigarettes (EC) have been shown to impair memory by disrupting the balance involving ROS and antioxidant enzymes, leading to oxidative stress. Vitamin C (VitC) is a strong antioxidant with cell protective efficacy and scavenges free radicals.</p><p><strong>Method: </strong>The present study evaluated VitC for potential protective effects against EC-induced memory impairment in rat models. The animals were exposed to EC for 2 hr/day, with a one-hour break in between, for five days per week over four weeks. Simultaneously, animals were administered Vitamin C at 100 mg/kilogram/bw/day via oral gavage five days/week/for four weeks. After the treatment and exposure period concluded, spatial learning and memory were evaluated using the Radial Arms Water Maze. Furthermore, the oxidative stress biomarkers levels (GSSG, GSH, GSH/ GSSG, TBARS, Catalase, and GPx) and brain-derived neurotrophic factor (BDNF) were measured in the hippocampus tissues. The findings indicated that EC had a detrimental effect on the short-term and long-term memory of the animals (p < 0.05). Additionally, EC decreased the levels of GPx, SOD, GSH, the GSH/GSSG ratio, and BDNF (p < 0.05).</p><p><strong>Results: </strong>Furthermore, the GSSG level was significantly elevated (p < 0.05) by EC. However, Vitamin C prevented impairment of memory and restored levels of biomarkers of oxidative stress and BDNF.</p><p><strong>Conclusion: </strong>To summarize, exposure to EC resulted in impairments of memory, both short-term and long-term. However, the administration of Vitamin C prevented these negative effects by its antioxidant properties.</p>","PeriodicalId":10905,"journal":{"name":"Current Neuropharmacology","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143398244","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Translational Informatics Driven Drug Repositioning for Neurodegenerative Disease.","authors":"Xin Zheng, Jing Chen, Yuxin Zhang, Shanshan Hu, Cheng Bi, Rajeev K Singla, Mohammad Amjad Kamal, Katsuhisa Horimoto, Bairong Shen","doi":"10.2174/011570159X327908241121062335","DOIUrl":"https://doi.org/10.2174/011570159X327908241121062335","url":null,"abstract":"<p><p>Neurodegenerative diseases represent a prevalent category of age-associated diseases. As human lifespans extend and societies become increasingly aged, neurodegenerative diseases pose a growing threat to public health. The lack of effective therapeutic drugs for both common and rare neurodegenerative diseases amplifies the medical challenges they present. Current treatments for these diseases primarily offer symptomatic relief rather than a cure, underscoring the pressing need to develop efficacious therapeutic interventions. Drug repositioning, an innovative and data-driven approach to research and development, proposes the re-evaluation of existing drugs for potential application in new therapeutic areas. Fueled by rapid advancements in artificial intelligence and the burgeoning accumulation of medical data, drug repositioning has emerged as a promising pathway for drug discovery. This review comprehensively examines drug repositioning for neurodegenerative diseases through the lens of translational informatics, encompassing data sources, computational models, and clinical applications. Initially, we systematized drug repositioning-related databases and online platforms, focusing on data resource management and standardization. Subsequently, we classify computational models for drug repositioning from the perspectives of drug-drug, drug-target, and drug-disease interactions into categories such as machine learning, deep learning, and networkbased approaches. Lastly, we highlight computational models presently utilized in neurodegenerative disease research and identify databases that hold potential for future drug repositioning efforts. In the artificial intelligence era, drug repositioning, as a data-driven strategy, offers a promising avenue for developing treatments suited to the complex and multifaceted nature of neurodegenerative diseases. These advancements could furnish patients with more rapid, cost-effective therapeutic options.</p>","PeriodicalId":10905,"journal":{"name":"Current Neuropharmacology","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143398002","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Informatics Approach Towards Targeting HTR1B Pathways in Neuropharmacology for Migraine Treatment.","authors":"Saleem Ahmad, Li Wang, Imran Zafar, Zain Abbas, Ahsanullah Unar, Mohamed Mohany, Salim S Al-Rejaie, Najeeb Ullah Khan, Ijaz Ali, Muhammad Shafiq","doi":"10.2174/011570159X341703250130064735","DOIUrl":"https://doi.org/10.2174/011570159X341703250130064735","url":null,"abstract":"<p><strong>Introduction: </strong>Migraine is a prevalent and debilitating neurological disorder, with current therapies often being ineffective and causing side effects. Recent studies in neuropharmacology present the serotonin 1B receptor (HTR1B) as a viable avenue of migraine treatment since it influences pain and vasoconstriction.</p><p><strong>Methods: </strong>This research broadly uses computational approaches to explain the 5-hydroxytryptamine receptor 1B (HTR1B) pathways in neuropharmacology for migraine treatment. Text mining results reveal 25 essential genes, and network pharmacology provides complex mechanisms among genes and proteins, revealing a sophisticated network consisting of 41 nodes and 361 edges. The protein structure and function were elucidated through high-resolution protein modeling and validation, yielding significant new information. The structure has a resolution of 2.05 Å and a C-score of 0.30. The virtual screening explored the best ligands, which had binding affinities ranging from -13.8 to -9.6 kcal/mol from a set of 25 molecules. Docking results indicated that FDA-approved ligands showed high binding affinities, ranging from -11.4 to -12.5 kcal/mol among other natural and synthetic libraries. The pharmacokinetic profiles of the potential drugs showed significant diversity in their solubility and lipophilicity qualities (F(2,6) = 15.13, p = 0.004), suggesting different levels of safety and efficacy. MD simulation clarified the dynamic interactions between the protein and ligand at 100ns.</p><p><strong>Results: </strong>The RMSD values were stable within the 6.0-7.5 Å range, indicating a consistent structure. RMSF values revealed areas of flexibility in the protein. The toxicity risk assessment of Xaliproden indicated modest risks.</p><p><strong>Conclusion: </strong>This study provides a foundation for targeted HTR1B-based migraine therapies and highlights the value of informatics tools in accelerating drug discovery in neuropharmacology.</p>","PeriodicalId":10905,"journal":{"name":"Current Neuropharmacology","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143397983","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Determining the Interaction in a Drug Combination using the Dose-based or Effect-based Method.","authors":"Tinghe Yu, Tianyan Yu, Xinya Li, Min Li","doi":"10.2174/011570159X347472250130111339","DOIUrl":"https://doi.org/10.2174/011570159X347472250130111339","url":null,"abstract":"<p><p>The interaction in a drug combination can be assessed using either the method of Chou or Jin's method. The combination index in the former (i.e., CI-C) is calculated based on doses, while the latter (i.e., CI-J) is based on effects. This perspective demonstrates a correlation between 1/CI-C and CI-J when applied to both released and simulated data. Thus, 1/CI-C and CI-J are functionally equivalent for evaluating drug interaction. Combining these two indices is preferred; consistency shows a reliable verdict, and inconsistency indicates a requirement for further analyses. However, it has been observed that evaluating released data raises certain concerns.</p>","PeriodicalId":10905,"journal":{"name":"Current Neuropharmacology","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143397891","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluating Remimazolam for Procedural Sedation.","authors":"Genevieve Monanian, Brandon Yonel, Deborah Rupert, Alina Razak, Michelle DeLemos, Sergio D Bergese","doi":"10.2174/011570159X367968250117034551","DOIUrl":"https://doi.org/10.2174/011570159X367968250117034551","url":null,"abstract":"<p><p>Remimazolam, a novel short-acting benzodiazepine, has garnered interest in the realm of procedural sedation. Targeting a desired level of sedation requires a medication with both anesthetic and analgesic properties, particularly in non-operating room anesthetizing locations. Via gammaaminobutyric acid type A receptor agonism, Remimazolam has demonstrated organ-independent metabolism and rapid time to both onset and recovery and has efficacy for procedural sedation in clinical trials. This article provides a review of the current literature on the utility of remimazolam for procedural sedation.</p>","PeriodicalId":10905,"journal":{"name":"Current Neuropharmacology","volume":" ","pages":""},"PeriodicalIF":4.8,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143398070","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}