Central Nervous System Agents

中枢神经系统药剂
  • 文章类型: Journal Article
    中枢神经系统(CNS)疾病是主要的健康问题之一。然而,血脑屏障(BBB)使传统的口服和静脉给药CNS药物效率低下。鼻子和大脑之间独特的直接连接使得鼻腔给药在CNS药物递送中具有巨大的潜在优势。然而,鼻黏膜纤毛清除(NMCC)限制了药物递送系统的发展。适当的鼻凝胶粘度在一定程度上缓解了NMCC,基于结冷胶的凝胶,壳聚糖,卡波姆,纤维素和泊洛沙姆已被广泛报道。然而,鼻凝胶制剂设计和缓解NMCC的关键性能尚未明确讨论。本文总结了现有鼻凝胶系统中不同聚合物的凝胶配方,并试图为研究者深入研究凝胶基质抗NMCC的关键特性提供依据。
    Central nervous system (CNS) diseases are among the major health problems. However, blood-brain barrier (BBB) makes traditional oral and intravenous delivery of CNS drugs inefficient. The unique direct connection between the nose and the brain makes nasal administration a great potential advantage in CNS drugs delivery. However, nasal mucociliary clearance (NMCC) limits the development of drug delivery systems. Appropriate nasal gel viscosity alleviates NMCC to a certain extent, gels based on gellan gum, chitosan, carbomer, cellulose and poloxamer have been widely reported. However, nasal gel formulation design and key properties for alleviating NMCC have not been clearly discussed. This article summarizes gel formulations of different polymers in existing nasal gel systems, and attempts to provide a basis for researchers to conduct in-depth research on the key characteristics of gel matrix against NMCC.
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  • 文章类型: Meta-Analysis
    横纹肌溶解症是由包括药物和毒素在内的多种机制引起的潜在危及生命的病症。我们旨在调查精神活性物质中毒患者横纹肌溶解的发生率。在这次审查中,三个数据库(PubMed,Scopus,WebofScience)和搜索引擎(GoogleScholar)通过各种关键字进行了搜索。在对检索到的文件进行筛选后,提取纳入研究的相关数据,采用随机效应模型进行加权均差(WMD)分析。在海洛因中毒中观察到横纹肌溶解症的发生率最高(57.2[95%CI22.6-91.8]),苯丙胺(30.5[95%CI22.6-38.5]),和可卡因(26.6[95%CI11.1-42.1])。血尿素氮的合并效应大小(WMD=8.78,p=0.002),肌酐(WMD=0.44,p<0.001),与无横纹肌溶解症患者相比,横纹肌溶解症患者的肌酐磷酸激酶(WMD=2590.9,p<0.001)较高.我们的结果表明,与整个病房相比,ICU患者中精神活性物质中毒引起的横纹肌溶解的发生率很高。此外,在有海洛因和苯丙胺中毒的ICU患者中,横纹肌溶解发生率较高.因此,临床医生应该预测这种并发症,横纹肌溶解症监测仪,并在患者的临床过程早期制定适当的治疗方案。
    Rhabdomyolysis is a potentially life-threatening condition induced by diverse mechanisms including drugs and toxins. We aimed to investigate the incidence of rhabdomyolysis occurrence in intoxicated patients with psychoactive substances. In this review, three databases (PubMed, Scopus, Web of Science) and search engine (Google Scholar) were searched by various keywords. After the screening of retrieved documents, related data of included studies were extracted and analyzed with weighted mean difference (WMD) in random effect model. The highest incidence of rhabdomyolysis was observed in intoxication with heroin (57.2 [95% CI 22.6-91.8]), amphetamines (30.5 [95% CI 22.6-38.5]), and cocaine (26.6 [95% CI 11.1-42.1]). The pooled effect size for blood urea nitrogen (WMD = 8.78, p = 0.002), creatinine (WMD = 0.44, p < 0.001), and creatinine phosphokinase (WMD = 2590.9, p < 0.001) was high in patients with rhabdomyolysis compared to patients without rhabdomyolysis. Our results showed a high incidence of rhabdomyolysis induced by psychoactive substance intoxication in ICU patients when compared to total wards. Also, the incidence of rhabdomyolysis occurrence was high in ICU patients with heroin and amphetamine intoxication. Therefore, clinicians should anticipate this complication, monitor for rhabdomyolysis, and institute appropriate treatment protocols early in the patient\'s clinical course.
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  • 文章类型: Systematic Review
    目的:本综述的目的是研究催产素在该患者人群中有效性的人体研究证据。尽管兴奋剂使用障碍是一个主要的公共卫生问题,没有经过验证的药物治疗。心理社会干预显示效果有限,特别是在更严重的兴奋剂使用障碍病例中,而动物模型表明催产素可能是一种有用的治疗方法。
    方法:使用Medline进行文献检索,Embase,和PsychInfo进行。随后将搜索结果导入Covidence以确定相关研究。
    结果:本综述包括六项研究,其中两项是试点研究。尽管催产素在研究中耐受性良好,没有研究显示报告的可卡因使用或渴望有统计学意义的显著减少.一项研究表明,催产素增加了使用可卡因的欲望,尽管应该考虑参与者的人数。相比之下,一项研究显示,自我报告的可卡因使用量有减少的趋势。
    结论:现有研究不支持在兴奋剂使用障碍的管理中使用催产素;然而,纳入的研究样本量小,数量有限。有几个值得注意的发现与这篇综述的主要和次要结果无关,这是感兴趣的,值得进一步研究。我们为该研究领域的未来研究提供建议。考虑到目前可用的数据有限,在就催产素在兴奋剂使用障碍管理中的使用做出任何明确结论之前,还需要进一步的研究.
    The purpose of this review is to examine human study evidence on the effectiveness of oxytocin in this patient population. Despite stimulant use disorder being a major public health concern, there are no validated pharmacological treatments. Psychosocial interventions show limited effectiveness especially in the more severe cases of stimulant use disorder, whereas animal models suggest that oxytocin may be a useful treatment.
    A literature search using Medline, Embase, and PsychInfo was undertaken. Search results were subsequently imported into Covidence to identify relevant studies.
    Six studies were included in this review, two of which were pilot studies. Although oxytocin was well tolerated across studies, no study showed a statistically significant reduction in reported cocaine use or cravings. One study suggested oxytocin increased the desire to use cocaine, although the population of participants should be taken into consideration. In contrast, one study showed a trend towards reduced self-reported cocaine use.
    Available research does not support the use of oxytocin in the management of stimulant use disorder; however, included studies are small in sample size and limited in number. There were several noteworthy findings unrelated to this review\'s primary and secondary outcomes, which are of interest and warrant further research. We provide suggestions for future studies in this area of research. Considering the limited data available at this time, further studies are required before any definitive conclusions can be made regarding the use of oxytocin in stimulant use disorder management.
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  • 文章类型: Journal Article
    增加滥用各种类型的新精神活性物质(NPS)的患者使用的药物治疗的有效性的因素之一是肝脏的正常功能。然而,迄今为止发表的关于NPS肝毒性的文章仅涉及非特异性肝参数.本手稿的目的是回顾精神病学中肝毒性的三种先进标志物,即,骨桥蛋白(OPN),高迁移率族蛋白1(HMGB1)和谷胱甘肽脱氢酶(GDH,GLDH),and,在此基础上,确定应纳入滥用NPSs患者未来研究的建议.这将有可能确定NPS是否确实具有肝毒性作用或其他因素例如服用的其他物质或丙型肝炎病毒(HCV)感染,是负责任的。NPS滥用者特别容易感染HCV,出于这个原因,更重要的是确定哪些因素实际上显示了肝毒性作用。
    One of the factors that increase the effectiveness of the pharmacotherapy used in patients abusing various types of new psychoactive substances (NPSs) is the proper functioning of the liver. However, the articles published to date on NPS hepatotoxicity only address non-specific hepatic parameters. The aim of this manuscript was to review three advanced markers of hepatotoxicity in psychiatry, namely, osteopontin (OPN), high-mobility group box 1 protein (HMGB1) and glutathione dehydrogenase (GDH, GLDH), and, on this basis, to identify recommendations that should be included in future studies in patients abusing NPSs. This will make it possible to determine whether NPSs do indeed have a hepatotoxic effect or whether other factors, such as additional substances taken or hepatitis C virus (HCV) infection, are responsible. NPS abusers are at particular risk of HCV infection, and for this reason, it is all the more important to determine what factors actually show a hepatotoxic effect in them.
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  • 文章类型: Journal Article
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  • 文章类型: Journal Article
    留兰香属唇形科(唇形科)中的薄荷属,因其非凡的香气和商业价值而在世界范围内种植。留兰香精油的芳香分子,包括Carvone,Carveol,二氢香芹酮,二氢卡维醇和乙酸二氢卡维醇,已广泛应用于香精香料行业。除了他们的传统用途,这些芳族分子在其他应用领域(例如,医学,农业,食物,和饮料),特别是由于它们的抗菌作用,抗氧化剂,杀虫,抗肿瘤,抗炎和抗糖尿病活性。这篇评论介绍了来源,属性,留兰香芳香分子的合成与应用.此外,这篇综述集中在迄今为止描述的这些化合物的生物学特性,它们对某些疾病的治疗作用,以及未来的研究方向。这次审查将,因此,有助于将留兰香芳香分子作为天然和安全的替代疗法进行合理和经济的探索。
    Spearmint belongs to the genus Mentha in the family Labiatae (Lamiaceae), which is cultivated worldwide for its remarkable aroma and commercial value. The aromatic molecules of spearmint essential oil, including carvone, carveol, dihydrocarvone, dihydrocarveol and dihydrocarvyl acetate, have been widely used in the flavors and fragrances industry. Besides their traditional use, these aromatic molecules have attracted great interest in other application fields (e.g., medicine, agriculture, food, and beverages) especially due to their antimicrobial, antioxidant, insecticidal, antitumor, anti-inflammatory and antidiabetic activities. This review presents the sources, properties, synthesis and application of spearmint aromatic molecules. Furthermore, this review focuses on the biological properties so far described for these compounds, their therapeutic effect on some diseases, and future directions of research. This review will, therefore, contribute to the rational and economic exploration of spearmint aromatic molecules as natural and safe alternative therapeutics.
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  • 文章类型: Journal Article
    大麻二酚(CBD)是源自大麻的一组植物大麻素的一部分。对CBD的初步工作假定该化合物不活跃,但后来发现它表现出抗精神病药,抗抑郁药,抗焦虑药,和抗癫痫作用。近几十年来,证据表明CBD在调节线粒体过程中的作用,包括呼吸和生物能学,线粒体DNA表观遗传学,内在凋亡,线粒体和细胞内钙浓度的调节,线粒体裂变,融合和生物发生,线粒体铁蛋白浓度和线粒体单胺氧化酶活性调控。尽管取得了这些进展,目前的数据表明,不仅在CBD介导的影响程度方面存在矛盾的发现,也是影响的方向。例如,有数据表明CBD治疗可以增加,减少,或对内在细胞凋亡没有显著影响。细胞类型研究之间的差异,对CBD的细胞特异性反应,and,在某些情况下,CBD的剂量可能有助于解释结果的差异.大多数关于CBD和线粒体的研究都利用了超过人类最高记录血浆浓度的治疗浓度,建议未来的研究应集中在药代动力学研究中观察到的范围内的CBD治疗。这篇综述着重于理解CBD介导的线粒体功能调节的机制。强调神经细胞和组织的发现以及基于人体药代动力学的治疗相关性。
    Cannabidiol (CBD) is part of a group of phytocannabinoids derived from Cannabissativa. Initial work on CBD presumed the compound was inactive, but it was later found to exhibit antipsychotic, anti-depressive, anxiolytic, and antiepileptic effects. In recent decades, evidence has indicated a role for CBD in the modulation of mitochondrial processes, including respiration and bioenergetics, mitochondrial DNA epigenetics, intrinsic apoptosis, the regulation of mitochondrial and intracellular calcium concentrations, mitochondrial fission, fusion and biogenesis, and mitochondrial ferritin concentration and mitochondrial monoamine oxidase activity regulation. Despite these advances, current data demonstrate contradictory findings with regard to not only the magnitude of effects mediated by CBD, but also to the direction of effects. For example, there are data indicating that CBD treatment can increase, decrease, or have no significant effect on intrinsic apoptosis. Differences between studies in cell type, cell-specific response to CBD, and, in some cases, dose of CBD may help to explain differences in outcomes. Most studies on CBD and mitochondria have utilized treatment concentrations that exceed the highest recorded plasma concentrations in humans, suggesting that future studies should focus on CBD treatments within a range observed in pharmacokinetic studies. This review focuses on understanding the mechanisms of CBD-mediated regulation of mitochondrial functions, with an emphasis on findings in neural cells and tissues and therapeutic relevance based on human pharmacokinetics.
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  • 文章类型: Journal Article
    II组代谢型谷氨酸(mGlu)受体已成为在阿尔茨海默病(AD)等领域开发新的CNS疗法的有吸引力的潜在靶标,焦虑,认知障碍,抑郁症,和其他人。在这些受体上充当负变构调节剂(NAMs)的几种小分子已在动物模型中证明了功效和/或靶标参与,一个分子(脱胶剂)已经进入临床试验。
    本综述总结了2015年1月至2020年11月期间公布的专利申请。它分为三个部分:(1)小分子非选择性mGlu2/3NAMs,(2)小分子选择性mGlu2NAMs,和(3)小分子选择性mGlu3NAMs。
    在发现新型小分子mGlu2NAMs方面取得了很大进展。尽管如此,化学多样性仍然有限,扩张空间仍然存在。mGlu3NAM的进展较为有限;然而,一些有前途的分子已经被公开。阐明每种受体在与II组受体相关的疾病中的精确作用的过程已经开始。在未来几年中,对两种受体具有选择性NAM的动物进行持续研究将是至关重要的,以告知研究人员正确的化合物概况和患者群体以进行临床开发。
    UNASSIGNED: Group II metabotropic glutamate (mGlu) receptors have emerged as an attractive potential target for the development of novel CNS therapeutics in areas such as Alzheimer\'s disease (AD), anxiety, cognitive disorders, depression, and others. Several small molecules that act as negative allosteric modulators (NAMs) on these receptors have demonstrated efficacy and/or target engagement in animal models, and one molecule (decoglurant) has been advanced into clinical trials.
    UNASSIGNED: This review summarizes patent applications published between January 2015 and November 2020. It is divided into three sections: (1) small molecule nonselective mGlu2/3 NAMs, (2) small molecule selective mGlu2 NAMs, and (3) small molecule selective mGlu3 NAMs.
    UNASSIGNED: Much progress has been made in the discovery of novel small molecule mGlu2 NAMs. Still, chemical diversity remains somewhat limited and room for expansion remains. Progress with mGlu3 NAMs has been more limited; however, some promising molecules have been disclosed. The process of elucidating the precise role of each receptor in the diseases associated with group II receptors has begun. Continued studies in animals with selective NAMs for both receptors will be critical in the coming years to inform researchers on the right compound profile and patient population for clinical development.
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  • 文章类型: Journal Article
    Background Generic drug exchange is common practice in most healthcare systems. While generics certainly contribute to economic savings, the altered drug formulation might be associated with potential therapeutic problems. Given the narrow therapeutic windows in neurologic indications, any detrimental effect on the therapy can lead to significant consequences. Aim of the review This review aims to investigate potential problems related to a switch from brand-name to generic or from generic to generic drug products in patients with neurologic diseases. Method The review was conducted following the PICO framework and the PRISMA guidelines. MEDLINE and Scopus databases were searched for articles published in English and German language between January 1, 1995 and October 17, 2018. Studies included in this review were randomized controlled studies, reviews, systematic reviews, overviews, cohort studies and case-control studies. Studies excluded were letters, comments, authors view, congress or seminar papers and studies with a focus on economic impact or costs. Results were synthesized qualitatively. The primary outcomes were pharmacokinetic parameters such as the area under the curve (AUC), the peak serum concentration (cmax) or the time at which cmax is observed (tmax). Results The search identified 67 studies with a great variety of endpoints and study designs. The leading indication was epilepsy. Two small RCTs were found on lamotrigine switch. Analysis of the other studies found no significant differences in pharmacokinetic parameters when switching to generic drugs. A more heterogeneous picture was revealed regarding hospitalizations, breakthrough seizures, failure of therapy, adherence and patient concerns. Conclusion While most reports were of poor quality, lamotrigine was the drug with the best available data. Summarizing the results of the available studies, pharmacokinetic parameters of antiepileptic drugs show low deviation. In contrast, data on clinical parameters are less consistent. Some studies found increased seizure frequencies and adverse-drug events, while others showed no complications. Adherence and patient satisfaction seemed to be impaired. In daily practice, generic exchange in epilepsy should be a carefully balanced decision, conducted with great caution. Further research is needed, especially regarding neurologic indications other than epilepsy.
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  • 文章类型: Journal Article
    BACKGROUND: Electro-convulsive therapy (ECT) is the most effective treatment for treatment resistant mood disorders and catatonia. ECT also appears to be an effective treatment in combination with clozapine in the context of treatment resistant schizophrenia spectrum disorders. Although increasingly codified (guidelines on indications, contraindications, methods of implementation), the practice of ECT still lacks consensual protocols. The concomitant use of psychotropic and/or non-psychotropic medication is a common situation when ECT treatment is considered. To our knowledge, there is to date no summary of studies or case reports in France, nor any proposal for guidelines concerning the management of medication of the patient to whom ECT sessions are offered. Indeed, several particularities must be considered. This article proposes to specify for each pharmacological class the possible interaction between ECT and medication. A first section of this article will be devoted to non-psychotropic treatments, and a second section to psychotropic treatments. A practical summary table is also provided.
    METHODS: A review of the literature was conducted including all articles published prior to January 2019 referenced in Pub Med database, combining research with Medical Subject Headings \"Electroconvulsive Therapy\" and each following pharmacological class: \"Cardiovascular Agents\" \"Bronchodilator Agents\" \"Bronchoconstrictor Agents\" \"Theophylline\" \"Anticoagulants\" \"Hypoglycemic Agents\" \"Insulin\" \"Potassium\" \"Benzodiazepines\" \"Valproic Acid\" \"Carbamazepine\" \"Lamotrigine\" \"Lithium\" \"Antidepressive Agents\" \"Antipsychotic Agents\".
    RESULTS: After reading the titles, abstracts and whole articles, then searching for additional articles in the references, 50 articles were selected. A summary table summarizing the main risks and proposing a course of action has been produced.
    CONCLUSIONS: It is essential to take into account the specificity and the different physiological mechanisms involved in the ECT treatment in order to adjust the associated pharmacological treatments. The prescription for each molecule should be reviewed when ECT treatment is initiated.
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