Benign prostatic hyperplasia (BPH) is one of the most prevalent human diseases and a major cause of lower urinary tract symptoms (LUTS). Some men respond to current medical treatment (mainly α-1 adrenoreceptor antagonists and 5 α-reductase inhibitors), but a large proportion of patients continues to need a surgical procedure to treat resistant LUTS or even more serious complications of BPH, creating the emerging necessity for novel pharmacological therapies.
Oxitriptan may have a possible positive effect on BPH associated symptoms with probably no impact in sexual function (which is a common side effect of the current drugs for BPH associated symptoms). Also, improvement in symptoms could be higher than that of current drugs used for this condition.
This is a single-center parallel group, randomized clinical trial. The study will take place in Hospital de Braga (Urology department). Eligible patients will be randomized to receive tamsulosin 0.4mg (once a day, q.d.) or 5-HTP (5-hidroxitriptophan) 100mg (three times a day, t.i.d.), for 6 months.

开始日期2024-12-20

申办/合作机构

The Clinical Academic Center of Braga

ChiCTR2500100210

/ RecruitingN/AIIT

Probiotic products with high production of 5-HTP are used in clinical research to intervene in children with autism

开始日期2024-12-06

申办/合作机构

湖北省妇幼保健院（湖北省妇女儿童医院）

NCT05895747

/ Recruiting临床2期IIT

31P-MRS and Resting State Functional Connectivity Analysis of the Effects of 5-hydroxytryptophan and Creatine for Antidepressant Augmentation in Patients With SSRI/SNRI-resistant Major Depressive Disorder

This is a three-armed clinical trial examining the effect of 5-hydroxytryptophan and creatine monohydrate as augmenting agents for the treatment of depression. Subjects will be randomized between 5-HTP 100mg BID + creatine 5g daily, 5-HTP 200mg BID + creatine 10g daily, vs double placebo, for 8 weeks. The ability of the interventions to affect biomarkers associated with depression will be assessed using brain phosphorus magnetic resonance spectroscopy, functional connectivity imaging, and plasma serotonin levels.

开始日期2023-09-28

申办/合作机构

University of Utah

100 项与羟色氨酸相关的临床结果

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100 项与羟色氨酸相关的转化医学

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100 项与羟色氨酸相关的专利（医药）

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4,073

项与羟色氨酸相关的文献（医药）

2025-08-01·FOOD CHEMISTRY

Metabolomics unravels the formation pathway of advanced glycation end products in preserved egg yolk mediated by OH− during pickling

Article

作者: Xiang, Xiaole ; Dong, Shiqin ; Li, Shugang ; Huang, Yiqun ; Ye, Lin ; Yu, Zhuosi ; Chen, Le ; He, Yu

Metabolomics was first applied to explore the formation pathway and regulatory factors for advanced glycation end products (AGEs) in preserved egg yolk (PEY) during pickling. Most reactions that contributed to formation of AGEs, including oxidation and/or degradation of matrix/precursors and Maillard reaction, occurred primarily in PEY in early stage, and lipid oxidation occurred prior to protein oxidation. Additionally, the formation of N^ε-carboxymethyl-lysine (CML) in PEY was mainly attributed to glyoxal derived from D-glucuronic acid in early stage based on the correlation between metabolites and AGEs. Reactive oxygen radicals from oxidized lipids also promoted the enrichment of CML and N^ε-carboxymethyl-lysine (CEL). Moreover, during later stage, the accumulation of CEL was enhanced through methylglyoxal from Schiff bases, and acidic compounds could inhibit AGEs via hindering Maillard reaction. This manuscript pioneered the application of metabolomics to reveal the formation pathway of AGEs, and will provide new perspective on AGEs formation in foods.

2025-08-01·Journal of Clinical Sleep Medicine

Sleep-related painful erection: the first case in a child

Article

作者: Bruni, Oliviero ; Checchi, Martina Proietti ; Moavero, Romina ; De Stefano, Donata ; Volponi, Claudia ; Voci, Alessandra ; Tiralongo, Giuseppe ; Valeriani, Massimiliano

CITATION:

Tiralongo G, De Stefano D, Volponi C, et al. Sleep-related painful erection: the first case in a child. J Clin Sleep Med. 2025;21(8):1491-1494.

2025-07-01·HEART RHYTHM

Role of serotonin and serotonergic-related metabolites in the pathogenesis of vasovagal syncope

Article

作者: Chen, Zhongli ; Chen, Ruohan ; Yang, Jiandu ; Wu, Sijin ; Gao, Yuan ; Chen, Keping ; Dai, Yan ; Han, Jing ; Wu, Ying ; Cai, Mengxing

BACKGROUND:

Serotonin is an important neurohormone that regulates vascular tone and autonomic reflexes, though its pathophysiological role in vasovagal syncope (VVS) remains uncertain.

OBJECTIVE:

This study sought to explore the involvement of serotonin and serotonergic-related metabolites in the pathogenesis of VVS.

METHODS:

Sixty-six patients [mean age 45.6±17.0 years; 33 women (50%)] with recurrent VVS underwent a head-up tilt test (HUTT). Blood samples were collected from all patients in a resting supine position, with an additional sample obtained from HUTT-positive patients during syncope. Plasma and platelet serotonin levels and plasma concentrations of serotonergic-related metabolites-including serotonin's precursor 5-hydroxytryptophan (5-HTP), major metabolite 5-hydroxyindoleacetic acid, and synthesis source tryptophan-were measured using the liquid chromatography tandem mass spectrometry method.

RESULTS:

HUTT was positive in 45 (68.2%) patients and negative in 21 (21.8%) patients. Significant differences were observed in plasma 5-HTP and 5-hydroxyindoleacetic acid levels between HUTT-positive and HUTT-negative patients (P<.001 and P=.040, respectively) as well as before and after syncope (P<.001 for all), whereas no significant changes were found in serotonin and tryptophan levels. Notably, plasma serotonin levels significantly increased during syncope in patients with drug-free VVS (P=.037), and a greater change in serotonin correlated with a shorter time to syncope (R²=0.38; P=.015). Furthermore, certain serotonergic-related metabolites exhibited significant correlations with hemodynamic changes during VVS episodes, with 5-HTP demonstrating the highest sensitivity.

CONCLUSION:

Despite the unchanged plasma and platelet serotonin levels, certain serotonergic-related metabolites significantly changed and correlated with hemodynamic parameters during VVS episodes, suggesting the potential involvement of an altered serotonergic metabolic pathway in VVS.

项与羟色氨酸相关的新闻（医药）

2025-04-29

·生物世界

Cell子刊：我国学者利用“后生元”破解便秘难题，效果超越益生菌

撰文丨王朝编辑丨王多鱼排版丨水成文慢性便秘是一种常见的胃肠道疾病，常伴有肠道炎症，对患者的生活质量影响很大。治疗通常包括饮食调整、排便习惯教育以及使用非处方泻药。尽管泻药容易获取，但它们常常会引起肠胃不适，近半数患者对此表示不满。2025 年 4 月 25 日，内蒙古农业大学张和平教授团队联合多家医疗机构，在 Cell 子刊 Cell Reports Medicine 上发表了题为：Efficacy of a postbiotic and its components in promoting colonic transit and alleviating chronic constipation in humans and mice 的研究论文。这项突破性研究揭示了后生元制剂 Probio-Eco 通过调控“肠道菌群-代谢物”双通路，显著改善慢性便秘。这项历时 2 年、覆盖 110 人的临床试验，或将改写全球 6 亿便秘人群的治疗方式！便秘治疗迎来新纪元：后生元是什么？对于慢性便秘，传统益生菌虽有一定效果，但存在存活率低、作用不稳定的痛点。“后生元”（Postbiotics）是益生菌发酵后的代谢产物，无需活菌即可起效。就像“菌群精华液”，含有琥珀酸、5-羟色氨酸等 30 多种活性成分，而且耐储存、见效快，还能绕过抗生素干扰。临床数据惊艳：3周见效，效果持续研究设计：110 名符合罗马 IV 诊断标准的慢性便秘患者，分两组进行 9 周交叉试验（3 周 Probio-Eco/安慰剂→2 周洗脱→3 周交叉治疗）。核心发现：排便革命：后生元治疗组完全自发排便（CSBM）频率提升 19%，排便费力评分降低32%；生活质量升级：腹胀烦恼减少 27%，身体不适感下降 26%；安全无忧：不良事件发生率比安慰剂组更低（5例 vs 7例）。肠道里的“信号兵”：双重代谢通路解密通过粪便宏基因组+代谢组分析，研究团队揭示了关键作用机制：1、琥珀酸-短链脂肪酸轴后生元显著提升丙酸、丁酸等“肠道润滑剂”，刺激肠壁分泌保护性粘蛋白 MUC2，效果比直接补充益生菌高 3 倍！2、色氨酸双通路5-羟色氨酸（5-HTP）通路：转化为血清素，激活肠道“动力开关”；3-吲哚丙烯酸：激活 AhR 免疫调节受体，减少肠道炎症；这就项同时按下了肠道的“加速键”和“消炎键”，双管齐下小鼠实验实锤：从粪便到基因的全证据链在洛哌丁胺诱导的便秘小鼠模型中：肉眼可见改善：粪便含水量恢复 86%，碳末排出时间缩短 40%；微观基因证据：肠屏障基因 Claudin-1 表达提升 2.3 倍，炎症因子 IL-6 下降 58%；菌群重构：有害菌 Erysipelatoclostridium 减少 79%，产丁酸菌 Roseburia 增加 3 倍；未来已来：后生元时代开启该研究首次实现“临床-动物-多组学”三维验证，目前 Probio-Eco 已进入产业化阶段。相比需冷藏的益生菌，后生元制剂可常温保存 18 个月，且适合与抗生素联用。更重要的是，这项研究不仅为慢性便秘治疗的突破，也为肠易激综合征、炎症性肠病等肠道疾病的治疗提供了新思路。论文链接：https://www.cell.com/cell-reports-medicine/fulltext/S2666-3791(25)00166-1设置星标，不错过精彩推文开放转载欢迎转发到朋友圈和微信群微信加群为促进前沿研究的传播和交流，我们组建了多个专业交流群，长按下方二维码，即可添加小编微信进群，由于申请人数较多，添加微信时请备注：学校/专业/姓名，如果是PI/教授，还请注明。点在看，传递你的品味

临床结果临床研究微生物疗法

2025-02-06

·戊戌数据

【中药同名同方报告】都梁软胶囊

一、处方溯源【药品名称】都梁软胶囊【处方组成】白芷，川芎。【剂型】胶囊剂【药品类型】非处方药（甲类）【功能主治】祛风散寒，活血通络。用于头痛属风寒瘀血阻滞脉络证者，症见头胀痛或刺痛，痛有定处，反复发作，遇风寒诱发或加重。【处方溯源】都梁丸（宋·王璆《是斋百一选方》）【方解】方中白芷辛温发散，芳香走窜，善入头部祛风散寒，通窍止痛，为君药；辅以辛散之川芎活血行气散风，使风除寒散，气血和调，为祛风散寒、活血止痛之要剂。二药合用，共奏祛风散寒，活血通络之功。【古方出处】《是斋百一选方》（宋·王璆）二、现代研究【中医理论】头痛是临床上常见的症状之一，按照头痛疾患的国际分类，将头痛疾患分为原发性头痛，继发性头痛，脑神经痛，中枢和原发性颜面痛及其他头痛[1]。头痛反复发作，起病急骤，其病机主要为风邪阻络、气血瘀滞。川芎、白芷均为祛风止痛之药，均可上行头目并分别入太阳经和阳明经，用于头痛眩晕，眉棱骨痛。都梁方源于《是斋百一选方》，由白芷单味药材组成，炼蜜为丸名"都梁丸"，能祛风散寒，主诸风眩晕。现代都梁方制剂出自《北京市中药成方选集》，由白芷、川芎2味组成，能散风止痛，主治感冒风寒、头痛眩晕、鼻塞不通、身热倦怠。其制剂主要包括都梁丸、都梁滴丸和都梁软胶囊等，现代临床上广泛用于偏头痛、慢性紧张型头痛等头痛类疾病[2]。【上市情况】【对照药品选择】“都梁软胶囊”已被现行《中国药典》（2020版）收载，质量标准明确，符合《同名同方研究技术指导原则》（试行）中“具有充分有效性、安全性”品种的规定，且该品种为重庆华森制药股份有限责任公司生产的独家品种，可以作为同名同方药的对照药品。【处方药味】【临床试验】 “都梁软胶囊”主要用于镇痛，治疗偏头痛、紧张性头痛等头痛类疾病。 1.治疗偏头痛的作用汪健[3]等采用随机对照法观察107例偏头痛患者的治疗情况，对照组给予口服安慰剂。治疗6周后，通过对患者前后疼痛程度、头痛发生率及持续时间进行对比，结果表明都梁软胶囊能有效降低偏头痛的发作次数，疼痛持续时间及疼痛程度。刘宪平[4]等通过对都梁软胶囊和氟桂嗪胶囊的对照治疗观察，发现都梁软胶囊的治疗效果明显优于后者，其主要作用机制是通过扩张血管、降低血管外周阻力，缓解脑动脉痉挛，增加脑血流量，改善脑缺血缺氧等症状，达到治疗头痛的目的。 2.治疗慢性紧张性头痛赵伊萌选取240例慢性紧张性头痛患者进行随机对照观察（对照组120例，氟西汀），发现都梁软胶囊能明显减少头痛的发作次数和发作时间，且无明显不良反应，整体治疗情况优于对照组。采用都梁软胶囊治疗慢性紧张型头痛能大大减少止痛药与精神类药物等的用药剂量，有助于减少患者服药所导致的临床不良反应[5]。【药理毒理】 1.缓解偏头痛的作用：都梁方制剂可通过调节血浆中内源性血管舒张神经递质一氧化氮(nitrogenmonoxide，NO)、一氧化氮合酶(nitricoxidesynthase，NOS)、内源性舒血管活性肽降钙素基因相关肽(calcitoningene-relatedpeptide，CGRP)及血管收缩神经肽内皮素(endothelin，ET)异常水平维持血管正常舒缩而缓解偏头痛[6]。 2.镇痛作用：韩笑等[7-9]观察到灌胃完全弗氏佐剂所致炎性疼痛小鼠都梁丸提取液6.68、13.36g/(kg·d)3d，灌胃完全弗氏佐剂所致炎性疼痛大鼠都梁丸提取液4.65、9.30g/(kg·d)5d可明显提高疼痛刺激痛阈，其镇痛作用机制可能与抑制外周组织心脏、肾上腺、皮肤上c-fos的表达，影响中枢单胺类神经递质5-HT、5-羟吲哚乙(5-Hydroxyindole-3-aceticacid，5-HIAA)、DA及NE含量，下调外周血清中痛觉相关经典神经递质5-羟色胺酸(5-hydroxytryptophan，5-HTP)、5-HIAA的含量有关。 3.抗炎作用：灌胃都梁丸、都梁软胶囊4、8g/(kg·d)3d均能使巴豆油型小鼠耳廓肿胀程度得到明显抑制[10]，川芎白芷水提醇沉剂单次腹腔注射给药5、15g/kg能明显改善大鼠蛋清性足跖肿胀程度[11]。 4.毒性研究：邓虹珠[12]等使用都梁软胶囊提取物进行毒理研究发现，都梁软胶囊的毒性靶器官为肝脏，能引起药物性肝炎，主要表现为肝脏肿大、血浆AST升高、肝细胞肿胀坏死，损害程度与剂量有关。停药后，病理损害减轻，证明该药品对肝脏的损害可逆。 5.不良反应：都梁方制剂治疗各种头痛及疼痛前后，受试者的肝功能、肾功能、心电图及血常规等安全性指标均未见报道，药物相关异常或临床症状加重，出现的不良反应有轻度恶心或呕吐、头晕、腹部不适或腹痛、嗜睡、乏力等，症状轻微，不作处理可自行缓解，其余未见明显不良反应[13-17]。【参考文献】 [1]中华医学会疼痛学分会头面痛学组.中国偏头痛诊断治疗指南[J].中国疼痛医学杂志，2011，17(2)：65-86. [2]韩李阳，鄢良春，田韦韦，等.都梁方制剂的现代药学、药理学及临床应用研究进展[J].中药药理与临床，2021，37(05). [3]汪健，罗兰，时文远，席刚明.都梁软胶囊治疗偏头痛临床疗效及安全性观察[J].中国中医急症，2009，18(09). [4]刘宪平，李浩，杨茂轩.都梁软胶囊治疗偏头痛95例临床观察[J].重庆医学，2008(07). [5]赵伊萌.都梁软胶囊治疗慢性紧张型头痛120例[J].中国药业，2012，21(18). [6]71Hou M,Tang Q,Xue Q,et al. Pharmacodynamic action and mechanism of Du Liang soft capsule,a traditional Chinese medicine capsule,on treating nitroglycerin-induced migraine[J]. J Ethnopharmacol，2017，(195): 231-237. [7]韩笑，刘文邱，德文，许建阳. 都梁丸提取液镇痛作用及对外周组织cfos基因表达影响的实验研究[J]. 中国实验方剂学杂志，2003，(4):34-36. [8]韩笑，徐祎，许建阳，等.都梁丸提取液的镇痛作用及其对小鼠脑组织中5-HT、5-HIAA、DA及NE含量的影响[J].中国中西医结合杂志，2004，(S1):29-31. [9]韩笑许建阳徐祎鲁燕侠邱德文. 都梁丸提取液镇痛作用及其对血清中5-HTP、5-HIAA含量的影响[J].中国中医基础医学杂志，2003， (12):41-42. [10]梅学仁，许俊然，田义红，等.都梁软胶囊治疗偏头痛药效学实验研究[J]. 中国医药导报，2006，(36):157-159. [11]徐军，李仪奎，陈蔚琳，等.川芎白芷药对(都梁丸)的药理作用研究[J]. 中药药理与临床，1992，(3):12-14. [12]邓虹珠，陈育尧，陈江华，肖炜.都梁软胶囊的药效及毒性试验[J].第一军医大学学报，2002；22(6). [13]张健，陈瑶，陈俊.都梁软胶囊治疗偏头痛临床疗效观察[J].亚太传统医药，2017，13(19):147-149. [14]YuS,HuY,WanQ,etal.AMulticente,Double-Blin,Randomized,Placebo-Controlled Trialto Evaluatethe Efficacyand Safetyof Duliang Soft Capsulein Patientswith Chronic Daily Headache[J].Evidence-Based Complementary and Alternative Medicine，2015，(2015):1-8. [15]汪健，罗兰，时文远，等.都梁软胶囊治疗偏头痛临床疗效及安全性观察[J].中国中医急症，2009，18(9):1402-1404. [16]康继根.都梁软胶囊治疗偏头痛疗效观察[J].中国社区医师(医学专业)，2011，13(5):130. [17]李雪莲.慢性每日头痛的临床特征及药物干预研究[D].重庆医科大学，2012. END ★ 点击下方卡片，发现更多精彩

2024-11-25

·Business Wire

Evecxia Therapeutics Announces Issuance of a US Patent Covering EVX‑301 in Development for Suicidal Ideation Crisis

RESEARCH TRIANGLE PARK, N.C.--( BUSINESS WIRE )--Evecxia Therapeutics—the first company dedicated to realizing the therapeutic potential of Serotonin Synthesis Amplification to treat central nervous system (CNS) disorders—today announced that the U.S. Patent and Trademark Office has issued U.S. patent US11779567 covering drug candidate EVX-301. The allowed claims broadly cover the EVX-301 method-of-treatment for therapeutic purposes, comprising putatively therapeutic doses, treatment durations, and pharmacokinetics. About EVX-301 EVX-301 is a proprietary intravenous infusion of 5-hydroxytryptophan, 5-HTP, the immediate precursor of serotonin. EVX-301 is designed to produce fast-onset brain Serotonin Synthesis Amplification, which convergent clinical evidence suggest could treat suicidal ideation with fast-onset (1-6). EVX-301 is being developed as rescue therapy for patients hospitalized with suicidal ideation crisis. EVX-301 has completed a Phase 1 trial in healthy volunteers with excellent safety and tolerability and evidence of fast-onset brain serotonin activation. About Suicidal Ideation U.S. suicide rates have increased 35% since year 2000, approaching 50,000 fatalities per year (Center for Disease Control). Every year 1 million patients are hospitalized in the U.S. with acute suicidal ideation crisis; but, there are no FDA-approved therapies. EVX-301 is being developed to address this urgent unmet need. About Evecxia Therapeutics Evecxia is the first company dedicated to realizing the therapeutic potential of Serotonin Synthesis Amplification to treat central nervous system disorders. Evecxia has two Phase 2 clinical-stage drug candidates in development. EVX-101 is being developed as an adjunctive treatment for depression and obsessive-compulsive disorder when first-line serotonin reuptake inhibitor antidepressants alone are inadequate. EVX-301 is being developed as rescue therapy for patients hospitalized for acute suicidal crisis. For additional information about Evecxia, please visit www.evecxia.com . References Lagerberg T, et al. (2022): Neuropsychopharmacology . 47:817-823. Cleare AJ, et al. (1995): Psychopharmacology . 118:72-81. Cherek DR, et al. (2001): Psychopharmacology . 157:221-227. Puhringer W, et al. (1976): Neurosci Lett . 2:349-354. Knutson B, et al. (1998): Am J Psychiatry . 155:373-379. Coccaro EF, et al. (2015): CNS Spectr . 20:295-302.

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100 项与羟色氨酸相关的药物交易

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KEGG	Wiki	ATC	Drug Bank
D07339	羟色氨酸	N06AX01	DB02959

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适应症	国家/地区	公司	日期
苯丙酮尿症	中国台湾	中国化学制药股份有限公司	1995-12-31
抑郁症	瑞士	-	-

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适应症	最高研发状态	国家/地区	公司	日期
自杀意念	临床1期	美国	Evecxia, Inc.	2023-04-20

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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


NCT05030129 (CTgov)	临床2期	脆性X综合征	15	Matching placebo for 5-Hydroxytryptophan+Ergoloid Mesylates (Ergoloid Mesylates (EM))	廠淵艱遞鬱膚蓋鬱醖壓 = 範鏇糧廠窪壓廠餘顧襯獵廠憲醖製醖淵鏇願襯 (鹹夢願簾範餘築構淵壓, 鑰簾艱顧淵餘選襯獵糧 ~ 蓋衊網範蓋遞襯製顧構) 更多	-	2024-09-19
NCT05030129 (CTgov)	临床2期	脆性X综合征	15	Ergoloid Mesylates+5-hydroxytryptophan (Ergoloid Mesylates (EM) and 5-hydroxytryptophan (5-HTP))	廠淵艱遞鬱膚蓋鬱醖壓 = 繭鹽積齋憲夢餘願積衊獵廠憲醖製醖淵鏇願襯 (鹹夢願簾範餘築構淵壓, 襯繭膚選襯構艱鏇築選 ~ 顧艱顧築夢醖網繭壓壓) 更多	-	2024-09-19
NCT04395183 (CTgov)	临床2期	重度抑郁症	43	placebo matched to 5-HTP+5-Hydroxytryptophan 100 MG (5-HTP + Placebo)	襯製願簾膚齋製夢簾窪 = 糧齋製顧淵淵醖製製艱鏇鏇觸襯獵鹹積襯範壓 (簾遞網獵窪醖遞築鑰製, 範積壓淵鹹鏇築糧製艱 ~ 齋糧築醖襯膚願範鹽鑰) 更多	-	2024-07-23
NCT04395183 (CTgov)	临床2期	重度抑郁症	43	placebo matched to 5-HTP+Creatine monohydrate (Creatine + Placebo)	襯製願簾膚齋製夢簾窪 = 膚餘積構繭鹽膚襯築製鏇鏇觸襯獵鹹積襯範壓 (簾遞網獵窪醖遞築鑰製, 網膚膚願製糧鹽蓋襯構 ~ 積膚願繭壓製顧獵築觸) 更多	-	2024-07-23
EUCTR2017-005059-10-BE \| NCT03574948 (Pubmed \| Gastroenterology)	临床2期	炎症性肠病	166	5-hydroxytryptophan	窪蓋襯醖淵鑰夢鹽憲繭(獵鹹願鹽窪鬱憲糧獵觸) = 淵製選觸網醖夢簾衊繭選膚窪齋鹽蓋夢積觸觸 (蓋願餘夢顧鏇餘鹽積衊, 1.97 ~ 4.03) 更多	不佳	2022-08-05
NCT02356107 (CTgov)	临床4期	缺氧 \| 重度抑郁症 \| 难治性抑郁症	15	Creatine monohydrate+5-hydroxytryptophan	遞衊憲鑰憲網鹹淵鹽遞(蓋艱遞簾選觸糧製襯壓) = 範糧鏇顧膚膚築獵積願鬱製艱齋醖範積憲遞繭 (膚觸憲獵淵廠積鹹蓋遞, 2.5) 更多	-	2018-01-04