Current Neuropharmacology最新文献

{"title":"Interleukin-17: A Putative Novel Pharmacological Target for Pathological Pain.","authors":"Shao-Jie Gao, Lin Liu, Dan-Yang Li, Dai-Qiang Liu, Long-Qing Zhang, Jia-Yi Wu, Fan-He Song, Ya-Qun Zhou, Wei Mei","doi":"10.2174/1570159X21666230811142713","DOIUrl":"10.2174/1570159X21666230811142713","url":null,"abstract":"<p><p>Pathological pain imposes a huge burden on the economy and the lives of patients. At present, drugs used for the treatment of pathological pain have only modest efficacy and are also plagued by adverse effects and risk for misuse and abuse. Therefore, understanding the mechanisms of pathological pain is essential for the development of novel analgesics. Several lines of evidence indicate that interleukin-17 (IL-17) is upregulated in rodent models of pathological pain in the periphery and central nervous system. Besides, the administration of IL-17 antibody alleviated pathological pain. Moreover, IL-17 administration led to mechanical allodynia which was alleviated by the IL-17 antibody. In this review, we summarized and discussed the therapeutic potential of targeting IL-17 for pathological pain. The upregulation of IL-17 promoted the development of pathological pain by promoting neuroinflammation, enhancing the excitability of dorsal root ganglion neurons, and promoting the communication of glial cells and neurons in the spinal cord. In general, the existing research shows that IL-17 is an attractive therapeutic target for pathologic pain, but the underlying mechanisms still need to be investigated.</p>","PeriodicalId":10905,"journal":{"name":"Current Neuropharmacology","volume":" ","pages":"204-216"},"PeriodicalIF":5.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10788884/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10003076","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Edible Herbal Medicines as an Alternative to Common Medication for Sleep Disorders: A Review Article.","authors":"Azar Hosseini, Leila Mobasheri, Hassan Rakhshandeh, Vafa Baradaran Rahimi, Zohreh Najafi, Vahid Reza Askari","doi":"10.2174/1570159X21666230621143944","DOIUrl":"10.2174/1570159X21666230621143944","url":null,"abstract":"<p><p>Insomnia is repeated difficulty in falling asleep, maintaining sleep, or experiencing lowquality sleep, resulting in some form of daytime disturbance. Sleeping disorders cause daytime fatigue, mental confusion, and over-sensitivity due to insufficient recovery from a sound sleep. There are some drugs, such as benzodiazepines and anti-histaminic agents, which help to sleep induction and insomnia cure. However, the prolonged administration is unsuitable because of tolerance and dependence. Therefore, the researchers attempt to find new medicines with lesser adverse effects. Natural products have always been good sources for developing new therapeutics for managing diseases such as cancer, cardiovascular disease, diabetes, insomnia, and liver and renal problems. Ample research has justified the acceptable reason and relevance of the use of these herbs in the treatment of insomnia. It is worth noting that in this study, we looked into various Persian herbs in a clinical trial and <i>in vivo</i> to treat insomnia, such as<i> Artemisia annua, Salvia reuterana, Viola tricolor, Passiflora incarnata</i>, lettuce, and <i>Capparis spinose</i>. According to research, herb extracts and fractions, particularly n-butanol fractions with non-polar agents, impact the benzodiazepine receptors and have hypnotic properties. Also, alkaloids, glycosides, flavonoids, saponins, and tannins in practically every plant are mentioned making them the popular natural compounds to help with sleep disorders and promote calmness.</p>","PeriodicalId":10905,"journal":{"name":"Current Neuropharmacology","volume":" ","pages":"1205-1232"},"PeriodicalIF":4.8,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10964091/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9727239","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Abusive use of Zolpidem as a Result of COVID-19 and Perspectives of Continuity of the Problem in the Post-Pandemic Period.","authors":"Wesley Dawison de Lima, Michael Douglas da Silva, Eurico de Souza Costa, Francisco Irochima Pinheiro, Eduardo Pereira de Azevedo, Ricardo Ney Cobucci, José Rodolfo Lopes de Paiva Cavalcanti, Fausto Pierdoná Guzen","doi":"10.2174/1570159X21666230920123401","DOIUrl":"10.2174/1570159X21666230920123401","url":null,"abstract":"<p><p>Zolpidem is a non-benzodiazepine hypnotic drug that works as a positive modulator of Gamma-Amino Butyric Acid-A (GABA-A) receptors, with high selectivity for α1 subunits. Given this selective binding, the drug has a strong hypnotic activity. Social isolation during the SARS-CoV-2 pandemic has contributed to increased rates of anxiety, depression, and insomnia. As a result, studies have pointed to a possible increase in the indiscriminate use of drugs with sedative effects, such as Zolpidem, during the pandemic. The aim of this work was to present prospective evidence that warns of the possibility of the abusive use of Zolpidem even after the pandemic. High rates of addiction to this drug have been reported around the world after the emergence of the coronavirus. Data from the National Survey on Drug Use and Health and from Medicaid support the continuing growth in prescription and indiscriminate use of Zolpidem during the pandemic and afterward. Therefore, there is enough evidence to support the indiscriminate use of this drug since the beginning of the pandemic. Rates of indiscriminate use of sedatives may continue to increase in the post-pandemic period, especially if strict control measures are not taken by health authorities.</p>","PeriodicalId":10905,"journal":{"name":"Current Neuropharmacology","volume":" ","pages":"1578-1582"},"PeriodicalIF":4.8,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11284723/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41115074","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"New Insights on Mechanisms and Therapeutic Targets of Cerebral Edema.","authors":"Pei Shang, Ruoyi Zheng, Kou Wu, Chao Yuan, Suyue Pan","doi":"10.2174/1570159X22666240528160237","DOIUrl":"10.2174/1570159X22666240528160237","url":null,"abstract":"<p><p>Cerebral Edema (CE) is the final common pathway of brain death. In severe neurological disease, neuronal cell damage first contributes to tissue edema, and then Increased Intracranial Pressure (ICP) occurs, which results in diminishing cerebral perfusion pressure. In turn, anoxic brain injury brought on by decreased cerebral perfusion pressure eventually results in neuronal cell impairment, creating a vicious cycle. Traditionally, CE is understood to be tightly linked to elevated ICP, which ultimately generates cerebral hernia and is therefore regarded as a risk factor for mortality. Intracranial hypertension and brain edema are two serious neurological disorders that are commonly treated with mannitol. However, mannitol usage should be monitored since inappropriate utilization of the substance could conversely have negative effects on CE patients. CE is thought to be related to bloodbrain barrier dysfunction. Nonetheless, a fluid clearance mechanism called the glial-lymphatic or glymphatic system was updated. This pathway facilitates the transport of cerebrospinal fluid (CSF) into the brain along arterial perivascular spaces and later into the brain interstitium. After removing solutes from the neuropil into meningeal and cervical lymphatic drainage arteries, the route then directs flows into the venous perivascular and perineuronal regions. Remarkably, the dual function of the glymphatic system was observed to protect the brain from further exacerbated damage. From our point of view, future studies ought to concentrate on the management of CE based on numerous targets of the updated glymphatic system. Further clinical trials are encouraged to apply these agents to the clinic as soon as possible.</p>","PeriodicalId":10905,"journal":{"name":"Current Neuropharmacology","volume":" ","pages":"2330-2352"},"PeriodicalIF":4.8,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11451312/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141160636","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multi-target Phenylpropanoids Against Epilepsy.","authors":"Teresa Carolliny Moreira Lustoza Rodrigues, Arthur Lins Dias, Aline Matilde Ferreira Dos Santos, Alex France Messias Monteiro, Mayara Cecile Nascimento Oliveira, Hugo Fernandes Oliveira Pires, Natália Ferreira de Sousa, Mirian Graciela da Silva Stiebbe Salvadori, Marcus Tullius Scotti, Luciana Scotti","doi":"10.2174/1570159X22666240524160126","DOIUrl":"10.2174/1570159X22666240524160126","url":null,"abstract":"<p><p>Epilepsy is a neurological disease with no defined cause, characterized by recurrent epileptic seizures. These occur due to the dysregulation of excitatory and inhibitory neurotransmitters in the central nervous system (CNS). Psychopharmaceuticals have undesirable side effects; many patients require more than one pharmacotherapy to control crises. With this in mind, this work emphasizes the discovery of new substances from natural products that can combat epileptic seizures. Using in silico techniques, this review aims to evaluate the antiepileptic and multi-target activity of phenylpropanoid derivatives. Initially, ligand-based virtual screening models (LBVS) were performed with 468 phenylpropanoid compounds to predict biological activities. The LBVS were developed for the targets alpha- amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), voltage-gated calcium channel Ttype (CaV), gamma-aminobutyric acid A (GABAA), gamma-aminobutyric acid transporter type 1 (GAT-1), voltage-gated potassium channel of the Q family (KCNQ), voltage-gated sodium channel (NaV), and N-methyl D-aspartate (NMDA). The compounds that had good results in the LBVS were analyzed for the absorption, distribution, metabolism, excretion, and toxicity (ADMET) parameters, and later, the best molecules were evaluated in the molecular docking consensus. The TR430 compound showed the best results in pharmacokinetic parameters; its oral absorption was 99.03%, it did not violate any Lipinski rule, it showed good bioavailability, and no cytotoxicity was observed either from the molecule or from the metabolites in the evaluated parameters. TR430 was able to bind with GABAA (activation) and AMPA (inhibition) targets and demonstrated good binding energy and significant interactions with both targets. The studied compound showed to be a promising molecule with a possible multi-target activity in both fundamental pharmacological targets for the treatment of epilepsy.</p>","PeriodicalId":10905,"journal":{"name":"Current Neuropharmacology","volume":"22 13","pages":"2168-2190"},"PeriodicalIF":4.8,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11337686/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141283275","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Peripheral Nervous System Pain Modulation.","authors":"Marcin Karcz, Christopher Gharibo","doi":"10.2174/1570159X21666230803100400","DOIUrl":"10.2174/1570159X21666230803100400","url":null,"abstract":"<p><p>The percutaneous technique of electrode insertion in the vicinity of the greater occipital nerves to treat occipital neuralgia was first described in the 1990s by Weiner and Reed. This subsequently stimulated awareness of peripheral nerve stimulation (PNS). The more recent advent emergence of a minimally invasive percutaneous approach by way of using ultrasound has further increased the interest in PNS as a viable alternative to more invasive techniques. PNS has become more popular recently and is increasingly used to treat various pain conditions. Its foundation is fundamentally based on the gate control theory, although the precise mechanism underlying its analgesic effect is still indefinite. Studies have demonstrated the peripheral and central analgesic mechanisms of PNS by modulating the inflammatory pathways, the autonomic nervous system, the endogenous pain inhibition pathways, and the involvement of the cortical and subcortical areas. Peripheral nerve stimulation exhibits its neuromodulatory effect both peripherally and centrally. Further understanding of the modulation of PNS mechanisms can help guide stimulation approaches and parameters to optimize the use of PNS. his chapter aims to review the background and mechanisms of PNS modulation. PNS is becoming one of the most diverse therapies in neuromodulation due to rapid evolution and expansion. It is an attractive option for clinicians due to the simplicity and versatility of procedures that can be combined with other neuromodulation treatments or used alone. It has a distinct role in the modulation of functional conditions.</p>","PeriodicalId":10905,"journal":{"name":"Current Neuropharmacology","volume":" ","pages":"65-71"},"PeriodicalIF":4.8,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10716886/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9918197","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Developmental Neuroendocrinology of Early-Life Stress: Impact on Child Development and Behavior.","authors":"Nicolas C Nicolaides, Christina Kanaka-Gantenbein, Panagiota Pervanidou","doi":"10.2174/1570159X21666230810162344","DOIUrl":"10.2174/1570159X21666230810162344","url":null,"abstract":"<p><p>Our internal balance, or homeostasis, is threatened or perceived as threatened by stressful stimuli, the stressors. The stress system is a highly conserved system that adjusts homeostasis to the resting state. Through the concurrent activation of the hypothalamic-pituitary-adrenal axis and the locus coeruleus/norepinephrine-autonomic nervous systems, the stress system provides the appropriate physical and behavioral responses, collectively termed as \"stress response\", to restore homeostasis. If the stress response is prolonged, excessive or even inadequate, several acute or chronic stress-related pathologic conditions may develop in childhood, adolescence and adult life. On the other hand, earlylife exposure to stressors has been recognized as a major contributing factor underlying the pathogenesis of non-communicable disorders, including neurodevelopmental disorders. Accumulating evidence suggests that early-life stress has been associated with an increased risk for attention deficit hyperactivity disorder and autism spectrum disorder in the offspring, although findings are still controversial. Nevertheless, at the molecular level, early-life stressors alter the chemical structure of cytosines located in the regulatory regions of genes, mostly through the addition of methyl groups. These epigenetic modifications result in the suppression of gene expression without changing the DNA sequence. In addition to DNA methylation, several lines of evidence support the role of non-coding RNAs in the evolving field of epigenetics. In this review article, we present the anatomical and functional components of the stress system, discuss the proper, in terms of quality and quantity, stress response, and provide an update on the impact of early-life stress on child development and behavior.</p>","PeriodicalId":10905,"journal":{"name":"Current Neuropharmacology","volume":" ","pages":"461-474"},"PeriodicalIF":5.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10845081/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9974358","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Basal Ganglia Downstream Control of Action - An Evolutionarily Conserved Strategy.","authors":"Johanna Frost-Nylén, William Scott Thompson, Brita Robertson, Sten Grillner","doi":"10.2174/1570159X21666230810141746","DOIUrl":"10.2174/1570159X21666230810141746","url":null,"abstract":"<p><p>The motor areas of the cortex and the basal ganglia both contribute to determining which motor actions will be recruited at any moment in time, and their functions are intertwined. Here, we review the basal ganglia mechanisms underlying the selection of behavior of the downstream control of motor centers in the midbrain and brainstem and show that the basic organization of the forebrain motor system is evolutionarily conserved throughout vertebrate phylogeny. The output level of the basal ganglia (e.g. substantia nigra pars reticulata) has GABAergic neurons that are spontaneously active at rest and inhibit a number of specific motor centers, each of which can be relieved from inhibition if the inhibitory output neurons themselves become inhibited. The motor areas of the cortex act partially via the dorsolateral striatum (putamen), which has specific modules for the forelimb, hindlimb, trunk, etc. Each module operates in turn through the two types of striatal projection neurons that control the output modules of the basal ganglia and thereby the downstream motor centers. The mechanisms for lateral inhibition in the striatum are reviewed as well as other striatal mechanisms contributing to action selection. The motor cortex also exerts a direct excitatory action on specific motor centers. An overview is given of the basal ganglia control exerted on the different midbrain/brainstem motor centers, and the efference copy information fed back <i>via</i> the thalamus to the striatum and cortex, which is of importance for the planning of future movements.</p>","PeriodicalId":10905,"journal":{"name":"Current Neuropharmacology","volume":" ","pages":"1419-1430"},"PeriodicalIF":4.8,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11097981/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9974363","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neuropathic Pain in Aged People: An Unresolved Issue Open to Novel Drug Approaches, Focusing on Painful Diabetic Neuropathy.","authors":"Nicoletta Marchesi, Foroogh Fahmideh, Alessia Pascale, Massimo Allegri, Stefano Govoni","doi":"10.2174/1570159X21666230807103642","DOIUrl":"10.2174/1570159X21666230807103642","url":null,"abstract":"<p><p>A majority of older patients suffer from neuropathic pain (NP) that significantly alters their daily activities and imposes a significant burden on health care. Multiple comorbidities and the risk of polypharmacy in the elderly make it challenging to determine the appropriate drug, dosage, and maintenance of therapy. Age-dependent processes play a contributing role in neuropathy given that diabetic neuropathy (DN) is the most common form of neuropathy. This narrative review is mainly focused on the drug treatment approach for neuropathy-associated pain in aged people including both drugs and dietary supplements, considering the latter as add-on mechanism-based treatments to increase the effectiveness of usual treatments by implementing their activity or activating other analgesic pathways. On one hand, the limited clinical studies assessing the effectiveness and the adverse effects of existing pain management options in this age segment of the population (> 65), on the other hand, the expanding global demographics of the elderly contribute to building up an unresolved pain management problem that needs the attention of healthcare providers, researchers, and health authorities as well as the expansion of the current therapeutic options.</p>","PeriodicalId":10905,"journal":{"name":"Current Neuropharmacology","volume":" ","pages":"53-64"},"PeriodicalIF":4.8,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10716885/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10008302","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Stress, Environment and Early Psychosis.","authors":"Lida-Alkisti Xenaki, Stefanos Dimitrakopoulos, Mirjana Selakovic, Nikos Stefanis","doi":"10.2174/1570159X21666230817153631","DOIUrl":"10.2174/1570159X21666230817153631","url":null,"abstract":"<p><p>Existing literature provides extended evidence of the close relationship between stress dysregulation, environmental insults, and psychosis onset. Early stress can sensitize genetically vulnerable individuals to future stress, modifying their risk for developing psychotic phenomena. Neurobiological substrate of the aberrant stress response to hypothalamic-pituitary-adrenal axis dysregulation, disrupted inflammation processes, oxidative stress increase, gut dysbiosis, and altered brain signaling, provides mechanistic links between environmental risk factors and the development of psychotic symptoms. Early-life and later-life exposures may act directly, accumulatively, and repeatedly during critical neurodevelopmental time windows. Environmental hazards, such as pre- and perinatal complications, traumatic experiences, psychosocial stressors, and cannabis use might negatively intervene with brain developmental trajectories and disturb the balance of important stress systems, which act together with recent life events to push the individual over the threshold for the manifestation of psychosis. The current review presents the dynamic and complex relationship between stress, environment, and psychosis onset, attempting to provide an insight into potentially modifiable factors, enhancing resilience and possibly influencing individual psychosis liability.</p>","PeriodicalId":10905,"journal":{"name":"Current Neuropharmacology","volume":" ","pages":"437-460"},"PeriodicalIF":5.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10845077/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10012251","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}