National, Phase III, Multicenter, Randomized, Open, Parallel, to Evaluate the Efficacy, Safety and Superiority of Cefalium® Compared to the Tylenol® in the Treatment of Migraine Attacks

National clinical trials, phase III, randomized, open, parallel, study of superiority, in which three hundred thirty-six (336) participants of both sexes, aged between 18 and 65 years will be randomly allocated to one of two treatment groups. The Group 01 will use Cefalium® and group 02 will use Tylenol®.

开始日期2020-04-01

申办/合作机构

Aché Laboratórios Farmacêuticos SA

100 项与 DRDs x COX 相关的临床结果

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100 项与 DRDs x COX 相关的转化医学

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0 项与 DRDs x COX 相关的专利（医药）

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项与 DRDs x COX 相关的文献（医药）

2025-01-01·Journal of Ethnopharmacology

Network pharmacology and experimental validation reveal the mechanisms of sniffing essential oil of Acori Tatarinowii rhizoma in treating olfactory dysfunction

Article

作者: Hu, Yilong ; Yang, Jingying ; Qi, Yupu ; Zhao, Yinan ; Miao, Jinxin ; Miao, Mingsan

ETHNOPHARMACOLOGICAL RELEVANCEAcorus tatarinowii Rhizoma, a traditional Chinese medicine known for open the orifices and transform phlegm, is used in the treatment of brain disorders. The essential oil of Acorus tatarinowii Rhizoma (EOAT) has demonstrated neuroprotective properties clinically. However, research into its effect on Olfactory Dysfunction (OD) remains limited.AIM OF THE STUDYThis study aimed to investigate the effects and mechanisms of sniffing EOAT on improving olfactory function in a 3-Methylindole (3-MI)-induced OD mouse model.MATERIALS AND METHODSThe research involved intraperitoneal injection of 3-MI to induce OD in mice. The effects of EOAT treatment were assessed on olfactory function, olfactory bulb (OB) pathology, inflammatory factors, olfactory marker protein (OMP), microglial activation, and related pathway proteins and mRNA.RESULTSBased on the GC-MS analysis results of EOAT and network pharmacology studies, we predicted 18 targets associated with the treatment of OD. SLC6A3, MAOB, DRD1, and PTGS2 were identified as the core targets of EOAT against OD. Molecular docking and KEGG enrichment results indicated that EOAT may exert anti-inflammatory effects by acting on the core target PTGS2, with its anti-inflammatory mechanism possibly related to the PI3K/Akt signaling pathway. Subsequent animal experiments confirmed that inhalation of EOAT significantly increased the body weight of OD model mice, shortened the foraging time, enhanced the expression of OMP in OB, reduced damage to the OB cells, and improved olfactory function. Meanwhile, EOAT significantly alleviated the inflammatory response in OB of OD model mice, inhibited the activation of microglial cells, and suppressed the expression of PI3K/Akt signaling pathway proteins and mRNA.CONCLUSIONEOAT inhalation could improve olfactory function in 3-MI-induced OD model. The underlying mechanism may be related to the modulation of the PI3K/Akt signaling pathway.

2024-12-01·Cellular and Molecular Neurobiology

A Pharmacogenomics-Based In Silico Investigation of Opioid Prescribing in Post-operative Spine Pain Management and Personalized Therapy

Article

作者: Lewandrowski, Kai-Uwe ; Schmidt, Sergio Luis ; Blum, Kenneth ; Elfar, John ; Wetzel, Franklin Todd ; Sharafshah, Alireza

AbstractConsidering the variability in individual responses to opioids and the growing concerns about opioid addiction, prescribing opioids for postoperative pain management after spine surgery presents significant challenges. Therefore, this study undertook a novel pharmacogenomics-based in silico investigation of FDA-approved opioid medications. The DrugBank database was employed to identify all FDA-approved opioids. Subsequently, the PharmGKB database was utilized to filter through all variant annotations associated with the relevant genes. In addition, the dpSNP (https://www.ncbi.nlm.nih.gov/snp/), a publicly accessible repository, was used. Additional analyses were conducted using STRING-MODEL (version 12), Cytoscape (version 3.10.1), miRTargetLink.2, and NetworkAnalyst (version 3). The study identified 125 target genes of FDA-approved opioids, encompassing 7019 variant annotations. Of these, 3088 annotations were significant and pertained to 78 genes. During variant annotation assessments (VAA), 672 variants remained after filtration. Further in-depth filtration based on variant functions yielded 302 final filtered variants across 56 genes. The Monoamine GPCRs pathway emerged as the most significant signaling pathway. Protein–protein interaction (PPI) analysis revealed a fully connected network comprising 55 genes. Gene–miRNA Interaction (GMI) analysis of these 55 candidate genes identified miR-16-5p as a pivotal miRNA in this network. Protein–Drug Interaction (PDI) assessment showed that multiple drugs, including Ibuprofen, Nicotine, Tramadol, Haloperidol, Ketamine, l-Glutamic Acid, Caffeine, Citalopram, and Naloxone, had more than one interaction. Furthermore, Protein–Chemical Interaction (PCI) analysis highlighted that ABCB1, BCL2, CYP1A2, KCNH2, PTGS2, and DRD2 were key targets of the proposed chemicals. Notably, 10 chemicals, including carbamylhydrazine, tetrahydropalmatine, Terazosin, beta-methylcholine, rubimaillin, and quinelorane, demonstrated dual interactions with the aforementioned target genes. This comprehensive review offers multiple strong, evidence-based in silico findings regarding opioid prescribing in spine pain management, introducing 55 potential genes. The insights from this report can be applied in exome analysis as a pharmacogenomics (PGx) panel for pain susceptibility, facilitating individualized opioid prescribing through genotyping of related variants. The article also points out that African Americans represent an important group that displays a high catabolism of opioids and suggest the need for a personalized therapeutic approach based on genetic information.Graphical Abstract

2024-07-05·Combinatorial Chemistry & High Throughput Screening

Study on Pharmacological Activities and Mechanisms of the Essential Oil of the Flowers of Hemerocallis citrina Baroni (EOFHCB) in the Treatment of Anxiety Disorders by GC-MS, Network Pharmacology, and Molecular Docking

Article

作者: Zhao, Huaxiang ; Liu, Ziyi ; Zhou, Xuan ; Lu, Zhen ; Jiao, Xiaoning ; Wang, Qiong ; Lu, Tao

Background:Hemerocallis citrina Baroni (Huanghuacai), a plant of the genus Hemerocallis in the family Asphodelaceae, is widely planted in China. Based on our survey results, the chemical compounds in the essential oil of the flowers of Hemerocallis citrina Baroni (EOFHCB) and relevant pharmacological activities have never been studied systematically.Objective:To preliminarily decipher the pharmacological activities and mechanisms of EOFHCB in the treatment of anxiety disorders by GC-MS, Network Pharmacology, and Molecular docking.Methods:EOFHCB compositions were identified using GC-MS, and their targets were predicted using Swiss Target Prediction databases. The targets of anxiety disorders were obtained by GeneCards, DisGeNET, and OMIM databases. The STRING database was used to construct the protein-protein interaction networks, and the DAVID database was used to carry out GO enrichment and KEGG pathway enrichment analysis. The EOFHCB-components-targetspathways- anxiety disorders network was constructed by Cytoscape software (Version 3.10.0). Finally, the result was verified by molecular docking.Results:28 chemical components were identified by GC-MS, including 3-furanmethanol (28.43%), 2-methyl-1-butanol (27.13%), nerolidol (10.62%), and so on, which correspond to 241 potential targets. Several 2440 biological processes, 187 cellular compositions, and 311 molecular functions were enriched by GO enrichment analysis and 174 pathways by KEGG enrichment analysis. The key targets are PTGS 2, SRC, DRD 2, ESR 1, MAOB, and SLC6A4. The most important pathway is the neuroactive ligand-receptor interaction.result:28 chemical components were identified by GC-MS, including 3-Furanmethanol(28.43%), 2-methyl-1-Butanol(27.13%), Nerolidol (10.62%) and so on, which correspond to 241 potential targets. 2440 biological processes, 187 cellular composition and 311 molecular functions were enriched by GO enrichment analysis, and 174 pathways by KEGG enrichment analysis . The key targets are PTGS 2, SRC, DRD 2, ESR 1, MAOB, and SLC6A4. The most important pathway is the neuroactive ligand-receptor interaction.Conclusion:EOFHCB exerts its therapeutic effects on anxiety disorders through multicomponents, multi-targets, and multi-pathways, which provided new ideas and methods for the in-depth research of aromatic Chinese medicine in the treatment of anxiety disorders.

项与 DRDs x COX 相关的新闻（医药）

2024-03-05

·精准药物

含吲哚药物结构与靶点，药理与SAR 研究归纳

吲哚是一种芳香杂环分子，具有一个苯环和一个含氮吡咯环组成的双环结构。吲哚中的氮原子提供一对孤对电子，形成共轭体系，从而稳定了吲哚结构。这对孤电子使吲哚化合物呈现弱碱性(pKa=16.2和pK,=17.6)。由于吡咯环的电子密度相对较高以及氮原子的共轭效应，吲哚可以在其吡咯环的3位发生亲电取代反应(图la)。图 1 (a) 全球有超过70种含有吲哚的合成药物在市场上销售，并被证明具有良好的医疗效果(图1b)。用于治疗的疾病包括糖尿病、癌症、白血病、丙型肝炎、心理障碍和其他临床问题。自2015年起，美国(FDA)专门批准了14种含吲哚药物，其中3种是在2021年批准的(图2)。二氢麦角胺(DHE,1)的化学结构中含有吲哚支架，对头颅血管平滑肌中的5-HT1b受体具有激动活性，治疗偏头痛。昂丹司琼(2)是一种血清素5-HT3受体拮抗剂，用于预防癌症治疗期间和手术后的恶心和呕吐(图3a)。图 3 (a) 双氢麦角胺（1）和昂丹司琼（2）的结构。(b) 双氢麦角胺(1)与其靶点（左）和昂丹司琼(2)与其靶点（右）的关键靶点相互作用。替加色罗(3)在临床相关水平上被认为是5-HT(4)受体的激动剂和5-HT(2B)受体的拮抗剂，其作用之一是使受损的胃肠道运动恢复正常。多拉司琼(4)用于中度致吐的癌症化疗以及术后恶心和呕吐的治疗(图5)。它是一种高效、选择性的血清素5-HT3受体拮抗剂。 Tropisetron（5）可抑制5HT3受体上血清素的活性，从而抑制放疗和化疗引起的呕吐。 Vilazodone(6)是5HT-1A受体的部分激动剂，专门抑制中枢神经系统对血清素的再摄取。在治疗偏头痛急性发作方面，三苯氧胺药物(5-羟色胺受体激动剂)比其他药物更有效、更耐受。这类药物具有起效快、用药时间长、不良反应少等优点。Sumatriptan(7),zolmitriptan(8),naratriptan(9), rizatriptan(10), almotriptan (11), frovatriptan (12), eletriptan (13), 和 oxitriptan (14) 是国外已商业化的曲坦类药物的代表。(图7)。环氧化酶(COX)被称为前列腺素G/H合成酶，而吲哚美辛是一种非特异性的可逆性环氧化酶抑制剂。吲哚美辛(18)属于吲哚-3-乙酸类，其官能团包括对氯苯甲酰基、甲基和甲氧基。它是一种非甾体抗炎药(NSAID), 具有消炎、镇痛和解热的特点(图11a)。 Acemetacin(19)是另一种强效非甾体抗炎药物，由吲哚-3-乙酸衍生而来(图12)。它主要通过酯分解代谢为吲哚美辛。 Etodolac(20)是一种非甾体抗炎药，具有消炎、镇痛和解热作用(图13a)。以前被认为是一种非选择性COX抑制剂，但现在被认为对COX-2的选择性是COX-1的5-50倍。 Carprofen(21)是兽医用作缓解老年犬关节炎症状的辅助疗法的一种非甾体抗炎药，人们认为卡洛芬(21)的作用机制是抑制环氧化酶的活性。帕金森病的药物 Cabergoline(22)是一种长效多巴胺受体激动剂，与D2受体有很强的亲和力，用于治疗高催乳素血症和帕金森综合症(图14a)。 Lisuride(23)可能是某些血清素受体的激动剂,也可能是多巴胺D1受体的拮抗剂。可降低催乳素水平，适量服用可阻止偏头痛，从药理上讲，(23)是还是一种帕金森氏症药物。治疗子宫脱垂的药物甲基麦角新碱(26)是一种麦角生物碱，临床上用于预防和治疗产后和流产后出血(图17)。这种药物与多巴胺D1受体结合，作为一种拮抗剂发挥作用，可增强平滑肌的张力、节奏和节律性收缩的幅度。治疗精神疾病的药物 sertindole（27）是一种抗精神分裂症药物，也是一种苯基吲哚衍生物。临床试验证实，(27)对低水平的多巴胺D2占位具有疗效。治疗神经系统疾病的药物吲哚洛尔(28)是一种非选择性β肾上腺素受体拮抗剂，用于治疗心房颤动、水肿、高血压和室性心动过速。卡维地洛(29)通过阻断β肾上腺素受体防止运动引起的心动过速，它对α-1肾上腺素能受体的作用可使血管平滑肌放松，从而降低外周血管阻力和血压。尼麦角林(30)是一种半合成麦角衍生物，可用于治疗认知功能障碍。这种药剂作为一种选择性α-1A肾上腺素能受体抑制剂用于临床(图20)。治疗生殖系统疾病的药物麦角新碱(32)是一种麦角生物碱，可用于控制妇女的产后和流产后出血。结构与活性关系明确的药物 Tezacaftor(41)属于用于治疗囊性纤维化(CFTR)增效剂。美国食品及药物管理局批准该药与ivacaftor联合用于治疗囊性纤维化(图28a)。该药物可在2至4小时内达到血浆浓度峰值。 2015年2月23日，FDA批准口服去乙酰化酶(DAC)抑制剂Panobinostat(42)用于治疗多发性骨髓瘤(图29a)。(42)在体外与人体血浆蛋白的结合率约为90%,这与其浓度无关。其吲哚环可以通过与Asn645的氢键相互作用为SAR创造一个稳定的框架(图29b)。结构与活性关系不完全明确的药物 Metergoline(52)是一种麦角衍生物，用于治疗女性高催乳素闭经症(图39)。通过靶向钠通道而非5HT受体来抑制钠通道的活性，从而导致泌乳素分泌减少。 Lurbinectedin(53)是一种抗癌天然产物。该药物在化疗中用于治疗转移性小细胞肺癌。Lurbinectedin(53)在临床试验中的治疗反应率和持续时间在2020年获得了加速批准。总体而言，在FDA批准的药物中，含有吲哚环的药物数量在不断增加。在药物分子中引入吲哚砌块也已成为药物化学和药物设计中的一种常见策略。现有的含吲哚药物因其特殊的结构，在抗癌、抗炎和抗病毒等方面具有显著的临床价值。参考文献：DOI: 10.1039/d3md00677h 内容来源于网络，如有侵权，请联系删除。

上市批准放射疗法

2023-06-11

·医药地理

2022年获批进口药品分析（精神障碍、呼吸系统、骨骼与肌肉、泌尿系统）

本文数据来自于CPM新药研发监测数据库（cpm.pharmadl.com）。精神障碍用药2022年NMPA批准的进口消化系统用药，共计24个（按照注册证号分类），获批品种较多的企业有H Lundbeck A/S（8个）、Aurobindo Pharma Ltd（4个）；涉及靶点排名前三的是5-HTT（11个）、ADRA2A（4个）、DRD2（4个）。在政策相关度方面，2022年获批的进口消化系统用药中，2022国家医保目录品种共有19个，带量采购招标品种有1个。呼吸系统用药2022年NMPA批准的进口呼吸系统用药，共计22个（按照注册证号分类），获批品种最多的企业是Organon Pharma (UK) Ltd（6个）。涉及较多的靶点是ADRB2（6个）、CYSLTR1（6个）。在政策相关度方面，2022年获批的进口血液和造血系统用药中，2022国家医保目录品种共有21个，没有带量采购招标品种。骨骼与肌肉用药2022年NMPA批准的进口内分泌及代谢调节用药，共计23个（按照注册证号分类），获批品种最多的企业是Organon Pharma (UK) Ltd（8个）。涉及靶点排名前三的是COX-2（12个）、IL6（4个）。在政策相关度方面，2022年获批的进口内分泌及代谢调节用药中，2022国家医保目录品种共有22个，没有带量采购招标品种。泌尿系统用药2022年NMPA批准的进口内分泌及代谢调节用药，共计10个（按照注册证号分类），获批品种最多的三家企业分别是Astellas Pharma Europe BV（8个）、Genzyme Europe BV（3个）、Meda Pharma Gmbh & Co Kg（2个）。涉及最多的靶点是ADRB3（4个）。在政策相关度方面，2022年获批的进口内分泌及代谢调节用药中，2022国家医保目录品种共有7个，没有带量采购招标品种。年度发布2023年《全球药研新动态》《中国医院市场用药格局》（2023版）2023年《数图药讯》权威发布2021年度中国医药工业百强榜单解读中国仿制药发展报告（2022版）医药行业专项报告中国医药中间体和原料药行业调研报告中国非甾体抗炎类原料药市场调研报告中国祛痰类原料药市场调研报告中国钙拮抗剂类原料药市场调研报告中国血管紧张素Ⅱ受体拮抗剂类原料药市场调研报告中国口服血糖调节类原料药市场调研报告中国中枢兴奋类原料药市场调研报告中国抗痛风类原料药市场调研报告中国脑血管病类原料药市场调研报告END如需获取更多数据洞察信息或公众号内容合作，请联系医药地理小助手微信号：pharmadl001

带量采购

2021-01-03

·创药网

神经精神疾病领域的创新靶标

神经精神疾病的患病率在全球范围内的不同人群中呈上升趋势，同时也给全球带来沉重的疾病负担，目前该类疾病仍有巨大的临床需求未得到满足。生物医药企业对神经精神疾病领域创新药物的研发仍抱有极大热情，一些新靶标如电压门控钠通道NaV1.7（SCN9A）、大麻素受体2型（CB2）和α7型烟碱型乙酰胆碱受体（α7nAchR）虽尚未有药物成功上市，但已有多个候选药物步入临床研发阶段。本文对这类靶标进行盘点并对在研药物加以概述。神经精神疾病包括神经系统疾病（Neurological disorders）和精神疾病（Psychiatric disorders），该类疾病的患病率在全球范围内的不同人群中呈上升趋势，同时也给全球带来沉重的疾病负担。生物制药行业对神经精神疾病的药物研发付出了巨大努力，近年来在某些疾病（如多发性硬化症、偏头痛等疾病）治疗上取得了令人惊喜的进步。然而，生物制药行业仍面临着开发创新药物以满足迫切医疗需求的巨大挑战。新机制、新靶标的识别具有重要意义，目前临床上也出现了一批针对尚未有药物成功上市的新型靶标药物，如靶向α-突触核蛋白（SNCA）、电压门控钠通道NaV1.7（SCN9A）、5-羟色胺6（5-HT6）、大麻素受体2型（CB2）、α7型烟碱型乙酰胆碱受体（α7nAchR）等靶标的药物。据统计，全球神经精神疾病已上市新药共计1211个，涉及的靶标超过300个，神经递质受体占据主导地位，如γ氨基丁酸A型受体（GABAAR）涉及的药物最多，有56个，其次是多巴胺受体D2（DRD2）（49个）、阿片类受体（40个）、毒蕈碱型乙酰胆碱能受体（mAChRs）（36个）、多巴胺受体（DRDs）（32个）、5-羟色胺2A受体（5-HT2A）（24个）。环氧化酶（COXs）包括COX-1和COX-2涉及的药物有87个，其中未分型的COXs涉及的药物有68个，是上市药物最多的靶标。电压门控离子通道如电压门控钠通道α亚基（SCNA）和电压依赖型钙通道（VDCCs）也是上市药物较多的靶标，分别有35和33个药物上市（图1）。图1：已上市药物涉及的靶标Top10 神经精神疾病领域临床在研药物（申报上市、临床Ⅰ期、临床Ⅱ期、临床Ⅲ期和临床未分期）共计1631个，涉及的靶标近600个，其中还未有药物成功上市的靶标有374个，已有药物进入后期研发阶段（申报上市及临床Ⅲ期）的靶标有129个。SNCA是在研药物涉及最多的靶标，共计12个药物，但这些药物都处于临床前期阶段，还没有临床Ⅲ期和申报上市的药物。其次，SCN9A、5-HT6受体、CB2、α7nAchR、代谢型谷氨酸受体5（mGluR5）在研药物数量都居于排行榜前列，分别有11、9、8、7、7个药物处于临床试验中。临床在研药物总数超过3个的靶标如图2所示。以下对部分未有上市药物的创新靶标在研药物进展进行介绍。图2：未有上市药物的创新靶标临床在研药物阶段分布本文其它内容请见《全球药物创新快讯》2020年第10期（总第103期）。 ////////// 【参考资料】 1. Xing C, Zhuang Y, Xu T H, et al. Cryo-EM structureof the human cannabinoid receptor CB2-Gi signaling complex. Cell, 2020, 180(4): 645-654. 2. 王佳杰, 王新童, 李远恒, 等. 用于改善认知障碍的靶向α7型尼古丁乙酰胆碱受体正向变构调节剂的研发现状. 药学进展, 2020, 44(8): 573-587. 3. 药渡数据库, 检索日期: 2020年11月20日. 4. Clarivate Cortellis数据库, 检索日期: 2020年11月20日. 版权声明：本文转自创药网，如不希望被转载的媒体或个人可与我们联系，我们将立即删除【关于药融圈】药融圈围绕我国生物医药产业链，针对生物医药大数据、技术和资本投资、药融园(产业园)等开展系列系统性工作，促进我国生物医药产业健康发展，完善产业链，共同面对全球合作和竞争。点分享点点赞点在看