The investigators aim to assess the interactions between the sympathetic nervous system and the vasculature in women across the menopause transition to better understand why aging women have a higher risk of cardiovascular disease.

开始日期2025-02-01

申办/合作机构

University of Missouri

NCT06620991

/ Not yet recruitingN/AIIT

Pre-operative Phentolamine Vs Intraoperative Esmolol Efficacy for Hypotensive Anesthesia in Functional Endoscopic Sinus Surgery

The aim of this study is to evaluate the efficacy of intra-operative phentolamine vs intraoperative esmolol for hypotensive anesthesia in functional endoscopic sinus surgery.

开始日期2024-10-10

申办/合作机构

Ain Shams University

NCT06422494

/ Not yet recruitingN/AIIT

The Role of the Adrenergic System in Hypoglycaemia Induced Inflammatory Response in People With Type 1 Diabetes and People Without Type 1 Diabetes-RAID-II

The goal of this trial is to study the effect that adrenaline has on the immune reaction seen during a low blood sugar. People with type 1 diabetes do not produce their own insulin. The cells in the pancreas that produce insulin are destroyed. People with type 1 diabetes require daily insulin administration. As a consequence of this insulin therapy the blood sugar can dip too low, causing symptoms such as confusion, irritation and tiredness. This is called hypoglycaemia. Hypoglycaemia has been associated with an increased risk for cardiovascular disease such as heart attacks. During hypoglycaemia the immune system is activated. The immune system consists of white blood cells which produce cytokines, these are proteins used to kill pathogens such as bacteria. During hypoglycaemia there are no pathogens but the cytokines are still produced, leading to unwanted damage. A previous study performed by our research group showed that the immune system activation caused by hypoglycaemia is associated with the stress hormone adrenaline. Adrenaline is released by the body in moments of stress such as during running or bungee jumping. Adrenaline is also released by the body during hypoglycaemia to increase the sugar level. Our hypothesis is that adrenaline activates the immune system during hypoglycaemia. Adrenaline acts in the body through two receivers, these are called alpha and beta receptors. These are present on almost all cells in the body especially on the immune cells. With the study we want to study the situation where there is a hypoglycaemia without the adrenaline. We will achieve this by lowering the blood sugar in participants. During the low blood sugar we will administer two drugs, which will attach themselves to the adrenaline receivers, the alpha and beta receptor. With this method we hope to block the adrenaline effects and with that block the immune response caused by adrenaline.

开始日期2024-09-01

申办/合作机构

Radboud University Medical Center

100 项与甲磺酸酚妥拉明相关的临床结果

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100 项与甲磺酸酚妥拉明相关的转化医学

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100 项与甲磺酸酚妥拉明相关的专利（医药）

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12,435

项与甲磺酸酚妥拉明相关的文献（医药）

2025-01-01·FARMACIA HOSPITALARIA

Review

作者: Gómez Sánchez, María T ; Tauste Hernández, Beatriz ; Fernández-Ginés, F Dámaso ; Cortiñas-Sáenz, Manuel ; Garrido Ortiz, Marta ; Sánchez Valera, Marina

PURPOSE:

To review and analyse the available literature on peripheral administration of noradrenaline (NA) with the aim of providing recommendations to ensure correct use and patient safety.

METHODS:

Systematic review on the databases PubMed, ISI Web of Science, SCOPUS, and Science Direct, using the following search terms: ("Noradrenaline" [Mesh]) AND ("Norepinephrine" [Mesh]) AND ("Vasopressors" [Mesh]) AND ("Peripheral infusions" [Mesh]) OR ("Extravasations" [Mesh]). A total of 1040 articles were identified. Animal studies and studies written in languages other than English were excluded. Finally, 83 articles were included.

RESULTS:

NA can be administered peripherally. The risk of extravasation should be taken into account, with phentolamine being the first pharmacological line of treatment. It has also been related to the appearance of thrombophlebitis, cellulitis, tissue necrosis, limb ischaemia, and gangrene, although its incidence seems to be low. The use of peripheral NA in children seems to be carried out without obvious complications. The use of standard concentrations is suggested to reduce the risk of errors. It is recommended to use 0.9% saline as the default diluent for peripheral NA.

CONCLUSIONS:

Peripheral infusions of NA could be a safe and beneficial option in early resuscitation provided that a number of guidelines are followed that reduce the likelihood of complications associated with this route.

2025-01-01·NEUROGASTROENTEROLOGY AND MOTILITY

Article

作者: Vergara, Patri ; Jimenez, Marcel ; Traserra, Sara ; Jiménez‐Altayó, Francesc ; Grao, Marc ; Trujillo, Sonia

Abstract:

Background:

Inhibitory neuromuscular transmission in the gastrointestinal tract is mediated by intrinsic nitrergic and purinergic neurons. Purines activate G protein‐coupled receptor P2Y1 receptors, increasing intracellular Ca2+ that activates small conductance calcium‐activated potassium (SKCa) channels. Little is known about the effect of adrenergic receptor activation on intestinal smooth muscle. In vascular tissue, stimulation of α‐adrenoceptors causes smooth muscle contraction, while their effect on intestinal tissue is poorly understood. This study aimed to pharmacologically characterize the effect of α‐adrenoceptor activation in the rat colon, which shares similar inhibitory pathways to the human colon.

Methods:

Muscle bath experiments were performed with the rat proximal, mid, and distal colon oriented both circularly and longitudinally.

Results:

The α1‐adrenoceptor agonist phenylephrine (PE) (10−8–10−5 M) evoked concentration‐dependent relaxations of the intestinal smooth muscle from all regions and orientations. However, in the mid‐circular colon at low PE concentrations, a contraction sensitive to 10−5 M phentolamine (non‐selective α‐adrenoceptor blocker), the neural blocker tetrodotoxin (TTX; 10−6 M), and atropine (10−6 M) was recorded. PE‐induced relaxations were insensitive to TTX (10−6 M) and the nonselective β‐adrenoceptor blocker propranolol (10−6 M). In contrast, PE‐induced relaxations were blocked by phentolamine (10−5 M), prazosin (10−6 M) (α1‐adrenoceptor blocker), and RS17053 (10−6 M) (α1A‐blocker), but not by yohimbine (10−6 M) (α2‐adrenoceptor blocker). Apamin (10−6 M), a SKCa channel blocker, abolished PE‐induced relaxations.

Conclusions:

Contractile responses in the circular muscle of the mid colon could be attributed to α‐adrenoceptors located on enteric cholinergic neurons. Stimulation of α1A‐adrenoreceptors activates SKCa channels to cause smooth muscle relaxation, which constitutes a signaling pathway that shares similarities with P2Y1 receptors.

2025-01-01·FARMACIA HOSPITALARIA

Administración segura de noradrenalina por vía periférica: una revisión sistemática

Review

作者: Gómez Sánchez, María T ; Tauste Hernández, Beatriz ; Fernández-Ginés, F Dámaso ; Cortiñas-Sáenz, Manuel ; Garrido Ortiz, Marta ; Sánchez Valera, Marina

PURPOSE:

To review and analyze the available literature on peripheral administration of noradrenaline (NA) with the aim of providing recommendations to ensure correct use and patient safety.

METHODS:

Systematic review on the databases PubMed, ISI Web of Science, SCOPUS and Science Direct, using the following search terms: ("Noradrenaline" [Mesh]) AND ("Norepinephrine" [Mesh]) AND ("Vasopressors" [Mesh]) AND ("Peripheral infusions" [Mesh]) OR ("Extravasations" [Mesh]). A total of 1,040 articles were identified. Animal studies and studies written in languages other than English were excluded. Finally, 83 articles were included.

RESULTS:

NA can be administered peripherally. The risk of extravasation should be taken into account, with phentolamine being the first pharmacological line of treatment. It has also been related to the appearance of thrombophlebitis, cellulitis, tissue necrosis, limb ischemia and gangrene, although its incidence seems to be low. The use of peripheral NA in children seems to be carried out without obvious complications. The use of standard concentrations is suggested to reduce the risk of errors. It is recommended to use 0.9% saline as the default diluent for peripheral NA.

CONCLUSIONS:

148

项与甲磺酸酚妥拉明相关的新闻（医药）

2024-12-30

·今日头条

湘雅二医院张晶晶团队：抗肥胖药物对心脏代谢和心理健康的影响

【导读】超重和肥胖给个人和社会带来了严重的健康挑战。这项研究重点关注减肥药物对心脏代谢健康、心理结果和不良事件的影响，从而促进肥胖症的个性化治疗。 2024年12月27日，中南大学湘雅二医院张晶晶教授团队在期刊《eClinicalMedicine》上发表了题为“Safety and effects of anti-obesity medications on weight loss, cardiometabolic, and psychological outcomes in people living with overweight or obesity: a systematic review and meta-analysis”的研究论文。研究结果表明，在减轻体重方面，替西帕肽是首选，其次是索马鲁肽。考虑到心脏代谢风险因素，替西帕肽的降压和降糖效果最佳，而索马鲁肽和利拉鲁肽则能降低MACEs风险。纳曲酮/安非他酮有血压升高的风险。酚妥拉明/托吡酯产生心理副作用的风险较高，应谨慎使用。 https://www-thelancet-com.libproxy1.nus.edu.sg/journals/eclinm/article/PIIS2589-5370(24)00599-6/fulltext 肥胖与减肥药物 01 体重持续下降10%以上，可改善许多与肥胖相关的并发症，包括预防和控制T2D、高血压、脂肪肝和阻塞性睡眠呼吸暂停，同时还能提高生活质量。基于证据的肥胖症治疗方法包括行为干预、营养改变、体育锻炼、药物疗法、减肥手术和抗肥胖器械。然而，行为干预后体重反弹很常见，仅进行体育锻炼对显著减轻体重的效果不大，而减肥手术的高成本和高风险限制了其使用。因此，药物疗法得到了长足的发展，当生活方式干预不足时，指南认可对肥胖或超重（体重指数≥27）并伴有相关合并症的非妊娠患者使用抗肥胖药物。目前，尚缺乏对这些减肥药物效果的综合性分析。这项研究旨在为药物治疗提供循证指导，并在临床实践中加强个性化体重管理。研究结果 02 在所有队列中，索马鲁肽与较高的胃肠功能紊乱风险相关，纳曲酮/安非他酮会升高收缩压，安非他酮会升高心率。GLP-1受体激动剂因其显著疗效而成为单纯超重/肥胖症患者和有体重相关并发症或合并症患者（尤其是后者）的首选药物。替西帕肽的减重效果最好，血压、血脂和血糖水平也有显著改善。索马鲁肽的减肥效果位居第二，并能显著改善心血管代谢。虽然利拉鲁肽在减轻体重或改善心血管代谢方面不是最有效的，但它能显著降低有体重相关并发症患者的MACE风险，这一点与索马鲁肽相似，表明它具有很强的心血管保护作用。不过，这3种药物都需要仔细监测胃肠道副作用。减肥药物对超重或肥胖症患者心脏代谢的影响。总结 03 1. 药物有效性评估：中度确定性证据显示，替西帕肽是最有效的减肥药物，其次是索马鲁肽。纳曲酮/安非他酮和酚妥拉明/托吡酯联合疗法的减重效果优于单一疗法，其中酚妥拉明//托吡酯的疗效优于纳曲酮/安非他酮。 2. 心脏代谢影响：中高度确定性证据表明，替西帕肽在降低血压、甘油三酯、空腹血糖、胰岛素和糖化血红蛋白水平方面效果最好。纳曲酮/安非他酮可能增加血压和心悸风险，而索马鲁肽和利拉鲁肽能显著降低体重相关并发症患者的MACE风险。 3. 心理影响：所有减肥药物都提高了IWQOL-Lite总分，替西帕肽的改善幅度最大。托吡酯和酚妥拉明/托吡酯可能增加焦虑、易怒和睡眠障碍的风险，托吡酯还可能增加抑郁或抑郁症状的发生率。 4. 不良事件风险：大多数减肥药因不良事件而停药的风险增加，替西帕肽的风险最高。胃肠功能紊乱是最常见的不良事件，索马鲁肽和利拉鲁肽增加胆石症风险，托吡酯和酚妥拉明/托吡酯易引起神经系统不良事件。 5. 治疗建议：替西帕肽在减轻体重和改善心脏代谢方面的疗效最高，索马鲁肽和利拉鲁肽能显著降低MACEs风险。纳曲酮/安非他酮和酚妥拉明/托吡酯由于潜在的心脏代谢和心理/神经不良反应，应谨慎使用。 6. 未来研究方向：需要进一步的研究来明确替西帕肽对MACEs的影响，以及探索索马鲁肽对脂质代谢的影响。参考资料： 1.Stefan, N. ∙ Häring, H.U. ∙ Hu, F.B. ∙ et al. Metabolically healthy obesity: epidemiology, mechanisms, and clinical implications Lancet Diabetes Endocrinol. 2013; 1:152-162 2.Flegal, K.M. ∙ Kit, B.K. ∙ Orpana, H. ∙ et al. Association of all-cause mortality with overweight and obesity using standard body mass index categories: a systematic review and meta-analysis JAMA. 2013; 309:71-82 【关于投稿】转化医学网（360zhyx.com）是转化医学核心门户，旨在推动基础研究、临床诊疗和产业的发展，核心内容涵盖组学、检验、免疫、肿瘤、心血管、糖尿病等。如您有最新的研究内容发表，欢迎联系我们进行免费报道（公众号菜单栏-在线客服联系），我们的理念：内容创造价值，转化铸就未来！转化医学网（360zhyx.com）发布的文章旨在介绍前沿医学研究进展，不能作为治疗方案使用；如需获得健康指导，请至正规医院就诊。热门推荐活动点击免费报名 🕓 线上｜2024年12月6日-2025年1月16日 ▶ 《我的2024》 🕓 全国｜2024年12月-2025年03月 ▶ 中国转化医学产业大会 🕓 上海｜2025年02月28日-03月01日 ▶ 第四届长三角单细胞组学技术应用论坛暨空间组学前沿论坛点击对应文字查看详情

临床结果AHA会议

2024-12-25

·GlobeNewswire-Health Care

Opus Genetics Receives FDA Agreement Under Special Protocol Assessment for Phase 3 Trial of APX3330 in Diabetic Retinopathy

Agreement Reached on Primary Endpoint and Phase 3 Trial Design Oral APX3330 is a Late-Stage Clinical Asset Available for Partnering Dec. 19, 2024 -- Opus Genetics, Inc. (Nasdaq: IRD), a clinical-stage ophthalmic biotechnology company developing gene therapies for the treatment of inherited retinal diseases (IRDs) and small-molecule drugs to treat other ophthalmologic disorders, today announced that it has reached agreement with the U.S. Food and Drug Administration (FDA) on a Special Protocol Assessment (SPA) for a Phase 3 clinical trial evaluating oral APX3330 for the treatment of moderate to severe non-proliferative diabetic retinopathy (NPDR). The SPA agreement reflects that the proposed Phase 3 trial design, endpoints, and planned analyses will be adequate to support a New Drug Application (NDA) submission for treatment of NPDR, subject to a successful outcome of the trial and review of all data in the NDA. The agreed primary endpoint is a reduction in 3-step or greater worsening on the binocular diabetic retinopathy severity scale (DRSS) score, compared to placebo. In the previous Phase 2 ZETA-1 trial, oral APX3330 showed the potential to slow or prevent clinically meaningful progression of DR and demonstrated a favorable safety profile. “This SPA agreement reflects our alignment with the FDA on the design of a Phase 3 trial for APX3330 and is a testament to the team’s developmental and regulatory acumen,” said George Magrath, M.D., Chief Executive Officer of Opus Genetics. "If successful in Phase 3 and subsequently approved, APX3330 has the potential to be a transformative treatment option for patients with NPDR. We believe that having this SPA in place will help de-risk certain regulatory aspects of this program. Our intention is to seek a partner for APX3330 to fund further development, as we focus our resources on advancing our gene therapy candidates for IRDs.” Diabetic retinopathy is a progressive eye disease which results in vision impairment and blindness among adults with diabetes. It is the leading cause of blindness in working age adults and impacts approximately 10 million patients in the US. APX3330 is a first-in-class, small molecule, oral inhibitor of the transcription factor regulator Ref-1 (reduction-oxidation effector factor-1). With a novel, multimodal mechanism of action, APX3330 modulates the downstream pathways regulated by Ref-1 – which involve angiogenesis (VEGF), oxidative stress (Nrf2) and inflammation (NFkB) – to restore homeostatic levels of angiogenenic, oxidative stress and inflammatory factors that are implicated across several ocular diseases, including DR, diabetic macular edema (DME), and age-related macular degeneration (AMD). APX3330 has shown a favorable tolerability profile in 12 clinical trials conducted in healthy, hepatitis, cancer, and diabetic subjects. Opus Genetics is a clinical-stage ophthalmic biotechnology company developing gene therapies to treat patients with inherited retinal diseases (IRDs) and other ophthalmologic disorders. The pipeline includes adeno-associated virus (AAV)-based investigational gene therapies that address mutations in genes that cause different forms of bestrophinopathy, Leber congenital amaurosis (LCA) and retinitis pigmentosa. The company’s most advanced gene therapy program is designed to address mutations in the LCA5 gene, which encodes the lebercilin protein and is currently being evaluated in a Phase 1/2 open-label, dose-escalation trial, with encouraging early data. BEST1 investigational gene therapy is designed to address mutations in the BEST1 gene, which is associated with retinal degeneration; a Phase 1/2 study is expected to be initiated in 2025. The pipeline also includes Phentolamine Ophthalmic Solution 0.75%, a non-selective alpha-1 and alpha-2 adrenergic antagonist being investigated to reduce pupil size, and APX3330, a novel small-molecule inhibitor of Ref-1 being investigated to slow the progression of non-proliferative diabetic retinopathy. Phentolamine Ophthalmic Solution 0.75% is currently being evaluated in Phase 3 trials for treatment of presbyopia and reduced dim (mesopic) light vision following keratorefractive surgery. The company has reached agreement with the FDA on an SPA for a Phase 3 trial to evaluate oral APX3330 for the treatment on NPDR. For more information, please visit www.opusgtx.com. The content above comes from the network. if any infringement, please contact us to modify.

基因疗法临床结果孤儿药

2024-12-20

·医药魔方

2025年值得关注的10项临床研究，针对社恐、暴食症、夜盲症……

GLP-1、ADC、双抗……是2024年创新药行业的高频词汇，相关交易层出不穷，以上热门靶点和创新技术为多个疾病领域带来了治疗突破，填补了诸多临床未满足需求。创新药的故事持续演绎，不断有创新疗法经过临床研究的验证走向成功。去年末，医药魔方从疾病负担和靶点角度筛选了8项值得关注的研究，其中有6项在2024年揭晓结果，喜悲参半。当下，基于医药魔方TrialCube数据库，我们从843项预计在2025年完成的III期临床试验中筛选出特别值得关注的10项研究，供大家参考。 2025年值得期待的10项III期研究注：医药魔方整理 NO.1 顽固的高血压有望迎来创新疗法在β受体阻滞剂、血管紧张素转换酶抑制剂（ACEI）、血管紧张素II受体抑制剂（ARB）等多种类型降压药物出现后，高血压患者的降压需求得到了极大的满足。但是，仍然有一半的患者无法实现较好的血压控制效果。大约25%的高血压源于醛固酮水平失调。醛固酮水平受肾素-血管紧张素-醛固酮系统（RAAS）调控，因而阻断RAAS是大部分现有降压药物的主要机制，例如阿利吉仑（肾素抑制剂，抑制血管紧张素原转化为血管紧张素I）、卡托普利（ACEI，抑制血管紧张素I转化为血管紧张素II）、缬沙坦（ARB，阻断血管紧张素II与其受体的结合）等。不过，目前还没有针对性抑制醛固酮（aldosterone）合成的药物上市。醛固酮合成酶（ALDOS，由CYP11B2基因编码）是一个较为新颖的研究方向，其关键之处在于可调控醛固酮合成的最后3个步骤，因而是抑制醛固酮合成的理想靶点。不过，由于CYP11B2基因与编码皮质醇合成酶的CYP11B1基因的序列同源性较高（93%），药物选择性差会导致患者的皮质醇水平也受到影响，因而控制选择性是开发ALDOS抑制剂必须解决的一个大难题。已上市的奥西卓司他（Novartis/Recordati）便是一款未能分离CYP11B1与CYP11B2选择性的产品，因而其仅获批了库欣综合征适应症。目前，全球已有2款针对高血压的ALDOS抑制剂进入III期阶段，即Baxdrostat（阿斯利康）和Lorundrostat（Mineralys Therapeutics）。临床前数据显示，Baxdrostat和Lorundrostat的CYP11B2/CYP11B1选择性分别为>100倍和374倍。这两款药物均已有II期研究数据披露。 Baxdrostat和Lorundrostat的II期研究降压数据从II期研究数据来看，Baxdrostat和Lorundrostat的降压效果差距不大，而且研究中均未出现皮质醇水平异常的情况。这两款药物的降压III期研究预计均将在2025年完成，届时可进一步知晓其抗高血压潜力。按登记数据来看，Lorundrostat将比Baxdrostat早7个月完成，我们可以先期待一下Lorundrostat的数据。 NO.2 丰富胶质母细胞瘤治疗选择大多数肿瘤类型已经拥有多样化的治疗选择，但胶质母细胞瘤（GBM）是其中的例外。GBM是最常见也是最具侵袭性的一种脑肿瘤，被称为“脑瘤之王”，约占原发性恶性中枢神经系统肿瘤的46.1%。手术和放化疗是这类患者的传统治疗策略，但预后不佳。恶性胶质瘤患者5年总生存率不足10%。目前，GBM的靶向治疗药物仅包括贝伐珠单抗和伯瑞替尼，其中后者仅限于PTPRZ1-MET融合基因的IDH突变型星形细胞瘤（WHO 4级）或有低级别病史的胶质母细胞瘤患者使用。除此之外，Novocure和再鼎医药合作开发的肿瘤电场疗法TTFields也可用于治疗GBM。研究表明，脂肪酸合成酶（FASN）是调节脂质代谢的最重要的蛋白质之一。许多实体瘤和血液肿瘤都过度表达FASN，包括复发性GBM等。地尼法司他（ASC40）是歌礼制药自Sagimet Biosciences引进的一款脂肪酸合成酶（FASN）抑制剂，可抑制肿瘤细胞能量供应和扰乱肿瘤细胞膜磷脂组成。 II期临床数据显示，GBM患者接受地尼法司他联合贝伐珠单抗治疗后，客观缓解率（ORR）达到了65%，其中完全缓解（CR）和部分缓解（PR）分别占17%和39%。此外，无进展生存期（PFS）达到6个月的患者比例为47%，明显高于过往贝伐珠单抗单药治疗的6个月PFS历史数据（16%）。歌礼制药针对GBM开展的III期ASC40-301研究将于2025年6月完成。该研究若能获得积极结果，地尼法司他有望成为GBM患者的突破性治疗药物。 NO.3 社恐人群的第二个希望社恐是一种严重的焦虑症，其特征是对社交或与表现相关的情况持续、强烈的恐惧。美国大约有2370万成人社恐患者，我国每年大约有560万人确诊社恐。目前尚无速效、按需治疗社恐的疗法获批。当前的护理标准为抗抑郁药和苯二氮卓类药物的超说明书使用，其具有显著的潜在副作用和安全性问题。此前鼻喷雾剂PH94B（fasedienol）曾在III期研究中展现出对社恐有疗效的迹象，但其疗效仍然存疑，并且临床设计也有不合理的地方，因此PH94B仍在反反复复验证其社恐治疗效果。 BNC210是Bionomics开发的一款靶向α7烟碱乙酰胆碱受体（α7 nAChR）的负向变构调节剂，已获FDA授予快速通道资格，用于治疗创伤后应激障碍（PTSD）、其他创伤和压力源相关疾病、急性治疗社恐和其他焦虑相关疾病。 2023年3月，BNC210（225mg或675mg）治疗社恐的II期PREVAIL研究顺利完成。数据显示，相比于安慰剂组，BNC210组患者的主观焦虑量表（SUDS）评分未显著改善（评分差异为5.69分，P=0.165），但结果具有临床意义且显示出了BNC210有益于改善社恐患者焦虑症状的趋势。因而，Bionomics还是决定在III期研究（AFFIRM-1）中继续评估BNC210的社恐治疗潜力。这项III期研究将在2025年8月完成。社恐人群能否拥有缓解社交焦虑症状的药物，相信明年可以知晓答案。 NO.4 “万能”GLP-1的下一个惊喜 GLP-1从2023年火到了2024年，这不仅仅是因为GLP-1药物具备强大的降糖和减肥效果，还因为其出色的“破圈”能力。迄今为止，以司美格鲁肽和替尔泊肽为代表的GLP-1药物已经在阻塞性睡眠呼吸暂停（OSA）、代谢障碍相关脂肪性肝炎（MASH）、慢性肾病（CKD）等疾病领域展现了其“溢出效应”。阿尔茨海默病将是GLP-1“破圈”计划的下一站。已经有不少文献揭示过GLP-1对阿尔茨海默病的有益治疗作用。近期，还有一项基于美国电子健康记录的模拟研究表明，接受司美格鲁肽（Ozempic）治疗的2型糖尿病患者，首次确诊阿尔茨海默病的风险降低了67%。这为诺和诺德开展的司美格鲁肽治疗阿尔茨海默病的III期研究提供了更高的成功确定性。 NO.5 强效降脂靶点有望迎来首个口服药物 Enlicitide（MK-0616）是默沙东开发的一款口服环肽类前蛋白转化酶枯草溶菌素9（PCSK9）抑制剂。PCSK9主要在肝脏表达，是“坏胆固醇”LDL-C升高的帮凶。PCSK9可与肝细胞表面负责清除LDL-C的受体结合，导致LDL-C堆积。针对高胆固醇血症的IIb期研究（n=381）结果显示，治疗第8周，接受Enlicitide（6/12/18/30mg，每日1次）治疗的患者的LDL-C水平均实现了统计学意义的降低，具体降幅分别为-41.2%、-55.7%、-59.1%和-60.9%。目前，全球共6款PCSK9靶向药物获批上市，分别为英克司兰（诺华）、托莱西单抗（信达生物）、依洛尤单抗（安进/安斯泰来）、阿利西尤单抗（再生元/赛诺菲）、伊努西单抗（康方生物）和昂戈瑞西单抗（君实生物），这6款产品均已在中国上市。此外，还有恒瑞医药的瑞卡西单抗和Lib Therapeutics/海森生物的莱达西贝普处于申请上市阶段。 PCSK9赛道的白热化竞争足以说明该靶点在降脂上的市场潜力。作为目前进展最快的口服PCSK9药物，Enlicitide的III期研究能否取得足够显著的疗效数据，值得期待。 NO.6 鼻喷疫苗扩圈至RSV领域虽然RSV赛道在今年遇到了不小的挫折，但是RSV疫苗的前景仍然值得期待，毕竟消除这个威胁婴幼儿和老年人生命的呼吸道疾病仍然是全球国家的共同目标。赛诺菲此前布局的RSV中和抗体Beyfortus（尼塞韦单抗）已经上市，可保护新生儿在第一个RSV流行季（当年10月-次年3月）不受感染。不过，该产品面临来自辉瑞、GSK和Moderna的RSV疫苗的激烈竞争。 RSVt疫苗（SP0125）是赛诺菲与美国国家过敏和传染病研究所（NIAID）合作开发的一款针对RSV感染的鼻喷减毒活疫苗，适用于全年龄段幼儿。可以说，RSVt疫苗是赛诺菲在RSV赛道选择的差异化策略。公开资料显示，RSVt疫苗可以在保护新生儿在第二个RSV流行季（次年4月-次年9月）不受感染。因此，Beyfortus和RSVt疫苗提供的双防线保障可以更大程度降低新生儿发生RSV感染的机率。若是能顺利完成III期研究，赛诺菲预计最早将在2026年提交该疫苗的上市申请。 NO.7 椎间盘退行性疾病的手术“救星” 椎间盘退行性疾病是一种常见的脊柱问题，主要影响中老年人群以及长期久坐人群。据估计，至少30%的30-50岁人群和大约90%的50岁以上人群会出现椎间盘退行。腰痛是这类疾病最常见的症状，其它症状还包括下肢疼痛麻木、间歇性跛行等。症状轻的患者可以通过物理治疗或者锻炼缓解症状，但是症状严重者需要手术治疗。椎体间融合术是目前治疗腰椎退行性疾病经典而有效的手术方法，其目的是通过将不稳定椎体进行融合消除因脊柱结构完整性丢失所致的脊柱病理性运动，以缓解疼痛、提高功能活动能力并改善生存质量。但据文献报道，腰椎融合术后不融合发生率可高达56%。长期未融合的腰椎假关节会带来诸多问题。因而，提高脊柱融合率是一个亟待解决的问题。 AGA111是安济盛开发的一款重组人骨形态发生蛋白6（BMP-6），与体内BMP主要拮抗剂Noggin的结合具有可逆性，低剂量下即可在体内实现良好的成骨效果。此外，AGA111采用了无免疫原性、无致炎性的内源性生物相容性材料——自体血凝块作为递送载体，可以有效减少局部水肿和炎性反应的风险。 II期研究结果显示，在椎体间融合术后12个月时，AGA111（0.25/0.5mg）组受试者的新骨形成比例中位数高于对照组（安慰剂+自体血凝块），疼痛评分较基线改善幅度也明显优于对照组。此外，AGA111在研究中还显示出了在促进脊柱融合、改善功能障碍等方面的初步临床疗效。 NO.8 夜盲症治疗的曙光夜盲症是指在光线昏暗环境下或夜晚视物不清或完全看不见东西的症状，其致病原因多种多样，例如缺乏维生素A、视网膜病变、遗传因素、屈光手术影响等。据统计，美国约有3800万例夜盲症患者，我国约有1500万例夜盲症患者。因维生素A缺乏引起的暂时性夜盲可以通过服用维生素A补充剂或摄入富含维生素A的食物来缓解症状，但因视网膜病变和遗传因素等原因导致的夜盲症还没有可用的治疗药物。 Nyxol（0.75%甲磺酸酚妥拉明滴眼液）是目前唯一一款处于III期阶段的在研夜盲症治疗药物，可通过阻断虹膜扩张肌上的α1肾上腺素能受体（α1-AR）和α2肾上腺素能受体（α2-AR）起到适度缩瞳作用（昏暗环境下瞳孔会放大），从而改善患者在昏暗环境下的视觉功能。 Nyxol已在2022年顺利完成了一项针对夜盲症的III期研究（LYNX-1）。结果显示，治疗第8天，Nyxol组达到中间视觉低对比度视力（mLCVA）改善10个及以上字母的患者比例更高（41% vs 22%，P<0.05），达到mLCVA改善15个及以上字母的患者比例也更高（13% vs 3%，P<0.05）。为了进一步验证Nyxol在夜盲症上的疗效和安全性，Opus Genetics（已被Ocuphire Pharma收购）开展了第2项III期研究（LYNX-2）。Opus Genetics预计在2025年第一季度便可以获得这项研究的顶线结果。 NO.9 暴食症治疗手段有望革新暴食症会导致胃肠道疾病、高血压、肥胖及由此引起的代谢和各系统功能紊乱等躯体问题，危害患者的身心健康。大约3.5%的女性和2%的男性存在暴食性障碍，超重或肥胖人群更为常见。目前，临床上的暴食症治疗手段包括心理治疗和药物治疗。药物治疗以抗抑郁药和食欲抑制药物为主，但真正获批可用于治疗暴食症的药物只有利右苯丙胺，而利右苯丙胺存在成瘾性风险。索安非托是一款多巴胺重摄取抑制剂和去甲肾上腺素重摄取抑制剂，已在2019年3月获FDA批准上市，用于治疗嗜睡。今年4月，Axsome Therapeutics宣布启动治疗暴食症的III期ENGAGE研究，在此之前其并未披露过相关临床数据。该药物是目前唯一一款正在III期研究中验证暴食症治疗潜力的药物。 NO.10 卵巢癌治疗选择有待丰富卵巢癌是治疗突破较少的常见肿瘤之一。目前，卵巢癌的标准治疗仍然是化疗。然而大多数患者会对化疗产生耐药性。耐药后卵巢癌的治疗药物仅包括PARP抑制剂、贝伐珠单抗和索米妥昔单抗，而PARP抑制剂和索米妥昔单抗的使用受限于生物标志物水平。化疗仍是卵巢癌的治疗方案中的重要一环，因而着力解决化疗耐药问题是药物研发方向之一。研究表明，化疗耐药的驱动因素之一可能是糖皮质激素，糖皮质激素过度激活其受体后会导致化疗对肿瘤细胞的杀伤能力下降。 Relacorilant是Corcept Therapeutics基于此机制开发的一款糖皮质激素受体拮抗剂，能够通过竞争性拮抗糖皮质激素的抗凋亡作用来恢复化疗敏感性并提高化疗效果。 Relacorilant的作用机制针对卵巢癌的II期研究结果显示，相比于白蛋白紫杉醇组，Relacorilant联合白蛋白紫杉醇组患者的无进展生存期显著延长（5.6 vs 3.8个月，HR=0.66，P=0.038），总生存期有所延长（HR=0.67，P=0.066）。推荐阅读 2025年，这20款重磅新药有望在中国获批 2024年医药并购交易：肿瘤降温，自免热潮 2025年全球畅销药TOP10预测，GLP-1产品占4款，Skyrizi飞升 2024年值得关注的8项临床研究：强迫症、万能GLP-1、首个口服Aβ靶向药…… Copyright © 2024 PHARMCUBE. All Rights Reserved. 欢迎转发分享及合理引用，引用时请在显要位置标明文章来源；如需转载，请给微信公众号后台留言或发送消息，并注明公众号名称及ID。免责申明：本微信文章中的信息仅供一般参考之用，不可直接作为决策内容，医药魔方不对任何主体因使用本文内容而导致的任何损失承担责任。

临床2期抗体药物偶联物临床3期临床结果临床成功

100 项与甲磺酸酚妥拉明相关的药物交易

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外链

KEGG	Wiki	ATC	Drug Bank
D00509	甲磺酸酚妥拉明	V03AB36 C04AB01	DB00692

研发状态

批准上市

10 条最早获批的记录,

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适应症	国家/地区	公司	日期
瞳孔散大	美国	Famy Life Sciences Pvt Ltd.	2023-09-25
勃起功能障碍	中国	上海复旦复华药业有限公司	1989-01-01
麻醉	美国	Novartis Pharmaceuticals Corp.	1952-01-30

未上市

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
夜盲症	临床3期	美国	Opus Genetics, Inc.	2023-04-27
老花眼	临床3期	美国	Opus Genetics, Inc.	2022-12-22
视力低下	临床3期	美国	Opus Genetics, Inc.	2020-12-30
开角型青光眼	临床2期	美国	Opus Genetics, Inc.	2019-05-28
失明	临床2期	美国	Opus Genetics, Inc.	2007-08-01

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临床结果

适应症

分期

评价

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


NCT04620213 \| NCT05134974 (MIRA-3, Literature) 人工标引	临床3期	瞳孔散大	553	phentolamine	選築鬱繭夢遞鑰獵網鑰(艱齋網鏇鑰範醖膚獵蓋) = 襯窪糧壓鹹窪齋獵範壓鏇獵獵鹽構糧繭憲鹹築 (繭蓋選網憲遞繭築選願 )	积极	2024-09-16
				placebo	選築鬱繭夢遞鑰獵網鑰(艱齋網鏇鑰範醖膚獵蓋) = 憲鹹窪選顧網構簾襯壓鏇獵獵鹽構糧繭憲鹹築 (繭蓋選網憲遞繭築選願 )
NCT04004507 (SNV, CTgov)	临床2期	夜盲症 \| 失明	24	Phentolamine Mesylate Ophthalmic Solution 1% (Phentolamine Mesylate Ophthalmic Solution 1%)	選鏇顧廠鑰獵醖蓋餘衊(願鹽衊遞鬱淵膚製顧顧) = 齋獵夢鏇繭衊膚積壓選鏇繭選衊鬱齋醖顧選餘 (壓鹽顧鑰艱憲觸鹹築鹽, 範範淵築觸鑰膚鑰遞衊 ~ 鑰壓鬱遞構壓齋夢網壓) 更多	-	2024-02-15
				Phentolamine Mesylate Ophthalmic Solution Vehicle (Placebo) (Phentolamine Mesylate Ophthalmic Solution Vehicle)	選鏇顧廠鑰獵醖蓋餘衊(願鹽衊遞鬱淵膚製顧顧) = 壓選鑰觸範艱築網衊範鏇繭選衊鬱齋醖顧選餘 (壓鹽顧鑰艱憲觸鹹築鹽, 膚築選鬱網鹽鹽觸醖築 ~ 願憲鬱蓋窪廠鑰鏇壓築) 更多
NCT04620213 \| NCT05134974 (MIRA-3, FDA) 人工标引	临床3期	瞳孔散大	553	Ryzumvi (MIRA-2)	積製壓淵壓鏇糧襯遞窪(築窪艱繭鑰鬱範淵網醖) = 艱積選膚築鹹淵鹹醖蓋鏇鬱製艱願顧糧憲夢願 (鏇餘繭齋齋製範糧積壓 )	积极	2023-09-25
				Placebo (MIRA-2)	積製壓淵壓鏇糧襯遞窪(築窪艱繭鑰鬱範淵網醖) = 衊齋醖鏇鹽壓膚齋蓋獵鏇鬱製艱願顧糧憲夢願 (鏇餘繭齋齋製範糧積壓 )
NCT04620213 (MIRA-2, CTgov)	临床3期	瞳孔散大	185	Phentolamine Ophthalmic Solution 0.75% (Phentolamine Ophthalmic Solution 0.75%)	觸夢夢襯鬱醖壓糧艱壓(艱獵願衊選選製廠齋窪) = 繭餘網築鑰窪鏇鹹廠艱齋簾憲鬱壓範膚膚構積 (廠簾遞夢選衊選築觸簾, 鹹構構鏇襯鏇艱壓選糧 ~ 餘遞餘餘築顧憲願選鑰) 更多	-	2023-08-14
				Phentolamine Ophthalmic Solution Vehicle (Placebo) (Phentolamine Ophthalmic Solution Vehicle)	觸夢夢襯鬱醖壓糧艱壓(艱獵願衊選選製廠齋窪) = 積壓製窪積齋窪齋獵築齋簾憲鬱壓範膚膚構積 (廠簾遞夢選衊選築觸簾, 衊夢範鏇鬱築壓壓範鏇 ~ 窪鹽衊齋簾襯觸鏇齋願) 更多
NCT04638660 (LYNX-1, CTgov)	临床3期	视力低下	144	Phentolamine Ophthalmic Solution 0.75% (Phentolamine Ophthalmic Solution 0.75%)	廠膚願壓製餘鏇鏇襯構(顧鹽遞鏇遞繭願願衊襯) = 鏇艱壓製積顧遞餘鏇鹹範觸鏇襯淵淵築廠夢願 (壓範衊憲艱壓願鹹鹽願, 膚蓋淵醖襯願衊鑰憲鹽 ~ 餘積夢夢憲觸積蓋艱網) 更多	-	2023-08-09
				Phentolamine Ophthalmic Solution Vehicle (Placebo) (Phentolamine Ophthalmic Solution Vehicle)	廠膚願壓製餘鏇鏇襯構(顧鹽遞鏇遞繭願願衊襯) = 衊遞鹹觸膚願膚顧艱願範觸鏇襯淵淵築廠夢願 (壓範衊憲艱壓願鹹鹽願, 蓋襯築獵獵衊壓觸壓鬱 ~ 範餘廠糧遞廠簾鹽鹹齋) 更多
NCT04675151 (CTgov)	临床2期	老花眼	150	LDP+POS (POS 0.75% First, Then LDP 0.4%)	願選築鑰壓鬱壓鑰淵鑰(襯築簾壓獵鹹願夢範醖) = 繭衊觸願齋築獵簾鑰積積簾鬱醖網顧願鬱製膚 (範襯構遞鬱膚憲獵顧選, 憲艱夢夢範糧蓋繭構糧 ~ 願糧遞蓋觸鹽鑰鹽範淵) 更多	-	2023-08-02
				LDP+POS (POS 0.75% First, Then LDP Vehicle)	願選築鑰壓鬱壓鑰淵鑰(襯築簾壓獵鹹願夢範醖) = 糧糧膚淵繭衊範鬱願鹽積簾鬱醖網顧願鬱製膚 (範襯構遞鬱膚憲獵顧選, 窪壓獵選壓網繭繭選願 ~ 艱壓醖範膚築遞蓋製憲) 更多
NCT05223478 (MIRA-4, CTgov)	临床3期	瞳孔散大	23	Phentolamine Ophthalmic Solution 0.75% (Phentolamine Ophthalmic Solution 0.75%)	鏇壓鹹窪襯選憲顧糧夢(獵憲夢觸築遞遞糧觸醖) = 糧夢鏇艱廠遞製製窪觸餘鏇艱繭鬱觸顧觸顧鹽 (淵鏇範觸顧醖壓製簾齋, 膚鏇夢夢選積醖遞遞鏇 ~ 廠築齋繭鑰鹹餘繭遞遞) 更多	-	2023-08-02
				Phentolamine Ophthalmic Solution Vehicle (Phentolamine Ophthalmic Solution Vehicle)	鏇壓鹹窪襯選憲顧糧夢(獵憲夢觸築遞遞糧觸醖) = 淵窪築築積鹹壓築構簾餘鏇艱繭鬱觸顧觸顧鹽 (淵鏇範觸顧醖壓製簾齋, 選蓋築壓襯夢餘鏇糧衊 ~ 鬱醖願範鏇襯鬱鹹鏇構) 更多
NCT05134974 (MIRA-3, CTgov)	临床3期	瞳孔散大	368	Phentolamine Ophthalmic Solution 0.75% (Phentolamine Ophthalmic Solution 0.75%)	獵獵獵範選壓餘衊獵積(鑰觸簾艱簾鏇製簾餘蓋) = 壓鬱鏇壓鏇艱齋鹹鑰鑰觸鑰鏇餘壓顧艱繭獵選 (積觸選鑰蓋鬱繭醖觸壓, 淵觸淵夢窪繭襯鑰膚蓋 ~ 糧齋鹽鬱簾製鹽餘遞網) 更多	-	2023-08-01
				Phentolamine Ophthalmic Solution Vehicle (Phentolamine Ophthalmic Solution Vehicle)	獵獵獵範選壓餘衊獵積(鑰觸簾艱簾鏇製簾餘蓋) = 夢構鹹觸餘觸願鏇襯衊觸鑰鏇餘壓顧艱繭獵選 (積觸選鑰蓋鬱繭醖觸壓, 簾獵簾鏇築憲齋艱醖窪 ~ 淵艱醖鑰窪鏇齋選襯醖) 更多
NCT03960866 (ORION-1, CTgov)	临床2期	开角型青光眼	39	Phentolamine Mesylate Ophthalmic Solution 1% (Nyxol Ophthalmic Solution 1%)	網艱襯獵獵艱鹽窪齋壓(膚積餘衊餘簾獵積窪獵) = 鬱醖艱憲遞範繭憲築壓製夢廠憲憲醖憲襯艱網 (膚繭積醖鹽鏇選積鏇膚, 壓鹽壓齋鬱鹹製餘鹽獵 ~ 鬱顧憲艱衊製蓋構選蓋) 更多	-	2023-07-12
				Phentolamine Mesylate Ophthalmic Solution Vehicle (Placebo) (Nyxol Ophthalmic Solution Vehicle)	網艱襯獵獵艱鹽窪齋壓(膚積餘衊餘簾獵積窪獵) = 構繭壓艱壓顧製願觸襯製夢廠憲憲醖憲襯艱網 (膚繭積醖鹽鏇選積鏇膚, 夢憲築繭壓構衊糧繭膚 ~ 顧積蓋簾願糧顧憲範構) 更多
MIRA-2 and MIRA-3 (ARVO2023)	临床3期	瞳孔散大	-	Phentolamine Ophthalmic Solution	窪繭築艱範觸窪窪餘顧(壓夢蓋夢夢鏇獵觸鹹積) = 構獵簾艱憲衊窪憲網鑰繭鏇襯廠鬱餘餘糧淵鏇 (選網鏇鏇艱築襯夢夢鹽 )	-	2023-06-01
				Placebo	窪繭築艱範觸窪窪餘顧(壓夢蓋夢夢鏇獵觸鹹積) = 齋鑰膚積窪憲願憲襯選繭鏇襯廠鬱餘餘糧淵鏇 (選網鏇鏇艱築襯夢夢鹽 )