A multicenter, open-label, uncontrolled, phase 1/2 study and extension study of ONO-5371 for symptoms of pheochromocytoma and paraganglioma caused by excess secretion of catecholamines(ONO-5371-02)

开始日期2015-10-26

申办/合作机构

Ono Pharmaceutical Co., Ltd.

NCT02152670

/ TerminatedN/AIIT

Understanding Dopamine Mechanisms in Cocaine Addiction Using AMPT and Methylphenidate With [11C]RAC/[11C]PHNO PET

Studies using positron emission tomography (PET) have been used with great success in demonstrating specific abnormalities in several facets of dopaminergic system function in human populations (Narendran and Martinez 2009). Among the first, most consistent, and broadly replicated of such findings in drug- (including cocaine) dependent individuals has been the reduction in subcortical (striatal) D2/3 receptors as imaged, most commonly, by the reversible, non-selective, D2/3 receptor antagonist radiotracer, [11C]raclopride. Certain dissociations on D2/3 availability by radioligand ([11C]raclopride vs. [11C]PHNO) and by brain region (striatum vs. SN; terminal vs. somatodendritic, respectively) are poorly understood in relationship to prior antagonist tracer results. In the current study the investigators will use pharmacological interventions (AMPT and methylphenidate) with both antagonist and agonist radiotracers to experimentally reconcile these discordant findings and clarify potential mechanistic inter-relationships.

开始日期2014-05-01

申办/合作机构

Yale University

NCT02179814

/ SuspendedN/AIIT

Neuronal Correlates of Catecholamine Depletion in Patients With Bulimia Nervosa Off Medication and Healthy Controls

Bulimia nervosa is a severe psychiatric disorder characterized by recurrent binge eating episodes followed by inappropriate compensatory behavior to prevent weight gain such as self-induced vomiting. With this project, the investigators want to investigate the role of the neurotransmitter dopamine in bulimia nervosa. Dopamine is reported to have an important influence on the neural reward system and is involved in the processing of gains and losses. The reward system is functionally connected to the individual perception of rewards in the environment. A previous study revealed that under catecholamine depletion including dopamine depletion women suffering from bulimia nervosa in their past reported mild bulimic symptoms and their reward processing became dysfunctional: their ability to use rewarding stimuli for task solving was diminished.
The aim of this study is to investigate the role of reduced dopamine availability in the development or maintaining of bulimia nervosa and in the dysfunctional processing of rewarding stimuli and negative visual information. Therefore, the investigators hypothesize that catecholamine depletion achieved by oral administration of alpha-methyl-paratyrosine (AMPT) will induce mild bulimic symptoms in females suffering from bulimia nervosa in their past. In addition, they will reveal dysfunctions in reward and emotional processing under catecholamine depletion. Using functional magnetic resonance imaging, the investigators propose that a reduced activation of the nucleus accumbens, a neural structure of the reward system, will be the neural correlate of this dysfunctional reward processing. Furthermore, the amygdala, a neural structure that is involved in emotional processing, will show a higher activation under catecholamine depletion. Genetic factors additionally have an influence on the dopaminergic system. Therefore, the investigators hypothesize that genetic factors, for example the COMT val-158-met polymorphism may have an effect on the behavioral and neural response to catecholamine depletion. In sum, this investigation may help to understand which changes in reward and emotional processing may lead to a reoccurrence of bulimic symptoms.
In future, the findings of this study may help to develop individual pharmacological and psychotherapeutical interventions to enhance the outcome of treatment.

开始日期2012-02-20

申办/合作机构

University of Bern

[+2]

100 项与甲酪氨酸相关的临床结果

登录后查看更多信息

100 项与甲酪氨酸相关的转化医学

登录后查看更多信息

100 项与甲酪氨酸相关的专利（医药）

登录后查看更多信息

1,385

项与甲酪氨酸相关的文献（医药）

2025-01-01·Food Frontiers

Acrylamide induces spatiotemporal metabolic profiling disturbance via targeting taurine and hypotaurine metabolism during early zebrafish development

作者: Wu, Yuanzhao ; Wan, Xuzhi ; Zheng, Ruonan ; Wang, Binjie ; Zhang, Yu ; Zhuang, Shulin ; Qin, Yazhou ; Yao, Weixuan ; Zhu, Li ; Song, Xiaoran ; Li, Haoyu ; Zhuang, Pan ; Wang, Anli ; Gao, Yuchen ; Zeng, Jia ; Huang, Yingyu ; Xu, Zhongshi ; Wang, Jiye ; Jiao, Jingjing ; Yao, Jianxin

AbstractAcrylamide, an endocrine‐disrupting emerging contaminant from both the environment and food processing, has been linked to cardiac developmental toxicity in zebrafish. However, the mechanisms involved in the cardiac developmental toxicity from long‐term exposure to acrylamide remain unclear. This study provides in‐depth evidence on the metabolic regulation of zebrafish embryos with acrylamide exposure. A comprehensive metabolites analysis of four different acrylamide exposures (0, 0.5, 1.0, and 2.0 mM) at different zebrafish developmental stages (6, 24, 48, 72, 96, and 120 h post fertilization, hpf) was performed. Metabolite changes throughout the zebrafish development (6–120 hpf) were closely associated with taurine and hypotaurine metabolism. The pattern of significantly changed metabolites revealed that acrylamide strongly disrupts taurine and hypotaurine metabolism related to a deficient cardiovascular system. Moreover, acrylamide exposure disrupted the de novo synthesis of taurine via cysteine sulfinic acid decarboxylase during early zebrafish embryogenesis. In addition, taurine supplementation (10 mM) effectively alleviates acrylamide‐induced deficient cardiovascular system. Our results demonstrate that acrylamide exposure has a detrimental effect on early heart development in zebrafish due to the inhibition of de novo synthesis of taurine.

2025-01-01·Domestic Animal Endocrinology

Physiological and metabolic effects of short-term dopamine reduction in healthy horses using a tyrosine hydroxylase inhibitor (alpha-methyl-para-tyrosine)

Article

作者: de Laat, Melody A ; Harris, Patricia A ; Bailey, Simon R. ; Galinelli, Nicolas C. ; Bamford, Nicholas J ; Warnken, Tobias ; Galinelli, Nicolas C ; Harris, Patricia A. ; Erdody, Madison L. ; Erdody, Madison L ; Sillence, Martin N ; Bailey, Simon R ; Bamford, Nicholas J. ; Sillence, Martin N. ; de Laat, Melody A.

Alpha-methyl-para-tyrosine (AMPT) is a reversible inhibitor of tyrosine hydroxylase, the rate-limiting enzyme in catecholamine synthesis. This study aimed to determine whether AMPT could reduce dopamine concentrations in horses. Six healthy adult Standardbred geldings were administered AMPT (40 mg/kg BW, orally) or placebo in a randomised crossover study design. Clinical examination findings were recorded, and blood samples were collected for up to 6 h after administration of AMPT or placebo, for measurement of blood glucose, plasma ACTH and cortisol concentrations, and plasma metabolomic analysis. Plasma prolactin concentration was determined as a proxy index of central dopamine reduction. No adverse clinical effects were detected after oral administration of AMPT, with heart rate, mean arterial pressure and blood glucose concentration not differing between AMPT treatment or placebo. Plasma prolactin concentration peaked 1 h after AMPT administration before returning to baseline at 2 h (for five horses) or 6 h (for one horse). Metabolomic analysis demonstrated a reduction in plasma dopamine (0.72-fold change; P=0.016) 1 h after AMPT treatment. Plasma ACTH and cortisol concentrations were not different between AMPT and placebo over time. A few metabolites associated with ketogenesis were increased, and certain amino acids decreased, at 1 h compared with baseline, for both AMPT treatment and placebo. Therefore, AMPT was effective in reducing both central and circulating dopamine concentrations in healthy horses following a single oral dose. Further pharmacokinetic and pharmacodynamic studies are warranted to optimise the dose and duration of AMPT treatment to achieve longer-term dopamine reduction. Plasma metabolomic findings suggested an interruption to energy flux at the time of sample collection, which may be relevant to nutritional studies in horses and warrants further investigation.

2025-01-01·Domestic Animal Endocrinology

Effect of short-term dopamine reduction on insulin sensitivity and post-prandial insulin and glucose responses in Standardbred horses

Article

作者: de Laat, Melody A ; Harris, Patricia A ; Bailey, Simon R. ; Galinelli, Nicolas C. ; Bamford, Nicholas J ; Warnken, Tobias ; Galinelli, Nicolas C ; Erdody, Madison L. ; Harris, Patricia A. ; Erdody, Madison L ; Sillence, Martin N ; Bailey, Simon R ; Bamford, Nicholas J. ; Sillence, Martin N. ; de Laat, Melody A.

The role of dopamine in the regulation of insulin secretion in horses is poorly understood and requires further investigation. Pituitary pars intermedia dysfunction (PPID) is associated with decreased activity of dopaminergic neurons which normally suppress peptide hormone secretion from the pituitary pars intermedia. A high proportion of horses with PPID also have insulin dysregulation (ID), characterised by post-prandial hyperinsulinaemia and/or tissue insulin resistance, which are risk factors for the development of laminitis. The aim of this study was to investigate the effects of alpha-methyl-para-tyrosine (AMPT), a tyrosine hydroxylase inhibitor that reduces dopamine production, on insulin sensitivity and the post-prandial insulin response to a glucose-containing meal. Six healthy Standardbred horses were enrolled in a placebo-controlled randomised crossover study, in which one dose of AMPT (40 mg/kg BW) or placebo was administered orally, prior to performing an in-feed oral glucose test (OGT) and a frequently sampled intravenous glucose tolerance test (FSIGTT). Dopamine reduction by AMPT was confirmed by an increase in plasma prolactin concentration and the lack of post-prandial increase in plasma dopamine concentration compared to placebo. Post-prandial insulin responses, both peak and AUCi, were increased after AMPT compared to placebo (P=0.048 and P=0.005, respectively), without affecting blood glucose concentrations. However, one dose of AMPT did not appear to affect tissue sensitivity as assessed by the FSIGTT. This study confirmed that dopamine plays a role in the regulation of insulin secretion in horses, as it does in other species, whereby the post-prandial release of dopamine into the circulation may inhibit pancreatic insulin secretion. Further studies are required to evaluate different dosing protocols for AMPT, and to further investigate the links between PPID, ID and laminitis risk in horses.

项与甲酪氨酸相关的新闻（医药）

2019-05-15

·BioSpace

Yamo Pharmaceuticals Presents Results from Phase 2 Study of L1-79 in Adolescents and Young Adult Males with Autism Spectrum Disorder at INSAR 2019

Yamo Pharmaceuticals, LLC announced the presentation of results from a Phase 2 study with L1-79 in the treatment of ASD. New York , May 14, 2019 (GLOBE NEWSWIRE) -- Yamo Pharmaceuticals, LLC , a clinical stage pharmaceutical company developing a novel therapy for autism spectrum disorder (ASD), announced the presentation of results from a Phase 2 study with L1-79 in the treatment of ASD. A poster entitled “An Open Label and Double Blind Randomized Placebo Controlled Pilot Study of L1-79 [D,L Alpha-Methyl-Para-Tyrosine (DL-AMPT)] for the Treatment of the Core Symptoms of Autism Spectrum Disorder (ASD) in Adolescent and Young Adult Males” was presented on Friday May 3rd during the International Society for Autism Research (INSAR) Annual Meeting in Montreal, Canada. The INSAR is a scientific and professional organization devoted to advancing knowledge about autism spectrum disorders. “The results from this study were very encouraging as positive trends were demonstrated across multiple efficacy measures of socialization in adolescent and young adult males with ASD, despite the small number of subjects and short duration of the study,” said J. Thomas Megerian, MD, PhD, Yamo Pharmaceuticals’ chief medical officer. “There was significant interest and enthusiasm generated by the poster presentation among INSAR attendees.” In the Phase 2 randomized, double-blind, and placebo-controlled study, 31 males between ages of 13 and 21 with a diagnosis of ASD received L1-79 100 mg, L1-79 200 mg or placebo administered three times per day (TID) for 28 days. Compared to placebo, study participants receiving L1-79 200 mg showed trends in improvements in aspects of social functioning and in repetitive restrictive behaviors (RRBs). While results did not reach statistical significance, the positive trends suggest that modulation of catecholaminergic neurotransmitters in ASD may be a viable strategy for therapeutic intervention. Yamo Pharmaceuticals is planning to conduct a larger study in adolescents and young adults with ASD to further assess the potential of L1-79. About L1-79 L1-79 is an investigational drug currently in clinical development by Yamo Pharmaceuticals for the treatment of the core symptoms of ASD. L1-79 was granted Fast Track Designation by the Food and Drug Administration in May of 2018. It acts as a tyrosine hydroxylase inhibitor and is expected to modulate the catecholaminergic pathways implicated in ASD. Clinical studies are planned to further investigate the potential of L1-79 to improve the core symptoms of ASD. About Autism Spectrum Disorder Autism spectrum disorder or autism refers to a group of complex neurodevelopment disorders that is defined in the Diagnostic and Statistics Manual of Mental Disorders V (DSM-5) by “difficulties in social communication and social interaction, and restricted and repetitive behavior, interests or activities.” In the US, it is estimated that 1 in 59 children have ASD, with boys being 3 to 4 times more susceptible than girls (Morbidity and Mortality Week Report Surveillance Summaries, 2018). Symptoms of repetitive and characteristic patterns of behavior and difficulties with social communication and interaction start early in childhood and continue throughout a person’s life. While the causes of ASD are not known, research suggests that both genes and environment play important roles. Since the severity, specific types of symptoms, and causes of ASD vary between individuals, it is referred to as a ‘spectrum’ disorder. Currently there are no approved pharmacological therapies which address the core symptoms of ASD. About Yamo Pharmaceuticals Yamo Pharmaceuticals is a clinical stage pharmaceutical company founded in 2015 to develop L1-79, a novel therapy with the potential to improve the core symptoms of Autism spectrum disorder. Yamo Pharmaceuticals is a privately held company. More information may be found at . Safe Harbor Statement This press release contains “forward-looking statements” concerning the development and commercialization of Yamo Pharmaceuticals’ products, the potential benefits and attributes of such products, and Yamo Pharmaceuticals expectations regarding its prospects. Forward-looking statements are subject to risks, assumptions and uncertainties that could cause actual future events or results to differ materially from such statements. These statements are made as of the date of this press release. Actual results may vary. Yamo Pharmaceuticals undertakes no obligation to update any forward-looking statements for any reason. Investor and Media ContactsChuck Bramlage, CEOcbramlage@yamopharma.comEugene Prahin, CFO212-610-1570eprahin@yamopharma.com

临床2期临床结果快速通道

100 项与甲酪氨酸相关的药物交易

登录后查看更多信息

外链

KEGG	Wiki	ATC	Drug Bank
D00762	甲酪氨酸	C02KB01	DB00765

研发状态

批准上市

10 条最早获批的记录,

后查看更多信息

适应症	国家/地区	公司	日期
嗜铬细胞瘤	美国	Bausch Health US LLC	1979-10-03

未上市

10 条进展最快的记录,

后查看更多信息

适应症	最高研发状态	国家/地区	公司	日期
迪格奥尔格综合征	临床前	美国	Bausch Health Americas, Inc.	2010-06-01
精神障碍	临床前	美国	Bausch Health Americas, Inc.	2010-06-01

登录后查看更多信息

临床结果

适应症

分期

评价

查看全部结果

研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


THU121 (ENDO2023)	N/A	Ascl1+ \| tyrosine hydroxylase \| dopa decarboxylase ... 更多	-	Metyrosine	膚網襯衊餘淵襯膚網蓋(顧醖觸齋顧遞憲膚齋遞) = 築願糧醖艱網遞襯糧構鏇淵遞製蓋襯積觸觸夢 (獵醖膚獵艱觸築顧鑰願 )	-	2023-10-05
				Benserazide	膚網襯衊餘淵襯膚網蓋(顧醖觸齋顧遞憲膚齋遞) = 餘膚顧製鑰膚夢廠製繭鏇淵遞製蓋襯積觸觸夢 (獵醖膚獵艱觸築顧鑰願 )
SAT311 (ENDO2023)	N/A	嗜铬细胞瘤 plasma metanephrines \| normetanephrine	-	Metyrosine	淵顧襯鏇膚簾簾選築襯(醖廠醖鏇製膚鹽餘夢齋) = 糧壓糧壓憲鹽鬱遞願築製觸淵築願遞繭選襯選 (構齋衊選窪繭繭製選鹹 ) 更多	-	2023-10-05
HOVON-87/NMSG-18 (EHA2019)	N/A	多发性骨髓瘤	190	MPR-R	(網餘製鹽簾願顧築糧襯) = 淵簾選襯襯蓋遞鑰簾襯選簾齋製繭膚繭糧衊淵 (簾齋構築壓顧餘蓋糧淵 ) 更多	-	2019-06-15
				MPT-T	(網餘製鹽簾願顧築糧襯) = 築獵艱艱範獵繭獵醖獵選簾齋製繭膚繭糧衊淵 (簾齋構築壓顧餘蓋糧淵 ) 更多
NCT01127503 (CTgov)	临床2期	迪格奥尔格综合征 \| 精神障碍	2	Metyrosine (Metyrosine)	製壓鹽鑰鹽鏇獵壓築鹽(鬱範遞獵鏇壓蓋選鏇衊) = 觸鹹簾鹹衊願遞艱壓壓鬱壓獵範壓遞鬱遞鏇鑰 (獵製製製餘獵築蓋壓廠, 鑰糧淵醖衊觸積築艱網 ~ 襯餘鑰夢遞網鬱艱範簾) 更多	-	2018-05-08
				Placebo (Placebo)	製壓鹽鑰鹽鏇獵壓築鹽(鬱範遞獵鏇壓蓋選鏇衊) = 鹽衊鏇齋艱襯網憲鑰鏇鬱壓獵範壓遞鬱遞鏇鑰 (獵製製製餘獵築蓋壓廠, 餘築襯鑰淵鑰憲蓋願鹹 ~ 積醖廠顧膚襯壓衊襯繭) 更多