Phase 2, multicenter, randomized, double-blind, placebo-controlled, four-period cross-over, dose-range finding study to evaluate the safety, tolerability and efficacy of Eltoprazine in the treatment of levodopa induced dyskinesia in patients with Parkinson's disease.

开始日期2015-08-18

申办/合作机构

Amarantus Bioscience Holdings, Inc.

NCT02439125 / Unknown status临床2期

Phase 2, Multicenter, Randomized, Double-blind, Placebo-controlled, 4-way Crossover, Dose-finding Study, of Eltoprazine Safety, Tolerability and Efficacy in the Treatment of Levodopa-induced Dyskinesia in Patients With Parkinson's Disease

The purpose of this study is to evaluate the safety, tolerability and efficacy of eltoprazine to treat levodopa-induced dyskinesia in patients with Parkinson's disease

开始日期2015-05-01

申办/合作机构

Amarantus Bioscience Holdings, Inc.

NCT01266174 / Completed临床2期

Randomized, Double-blind, Parallel Trial Comparing the Effects of Eltoprazine (Adjunct to Anti-psychotics) With Placebo in Adults With Schizophrenia, in Improving One or More Dimensions of Cognitive Impairment Associated With Schizophrenia

The purpose of this study is to determine if eltoprazine (as an adjunct to anti-psychotic medication) improves one or more aspects of cognitive impairment in adult schizophrenic patients.

开始日期2011-08-01

申办/合作机构

Amarantus Bioscience Holdings, Inc.

100 项与 5-HT1A receptor x 5-HT1B receptor x 5-HT2C receptor 相关的临床结果

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100 项与 5-HT1A receptor x 5-HT1B receptor x 5-HT2C receptor 相关的转化医学

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0 项与 5-HT1A receptor x 5-HT1B receptor x 5-HT2C receptor 相关的专利（医药）

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181

项与 5-HT1A receptor x 5-HT1B receptor x 5-HT2C receptor 相关的文献（医药）

2023-09-14·ACS Medicinal Chemistry Letters

Exploring Next-Generation Therapeutics: Morphic Mixtures and Specified Salts for the Treatment of Mental Disorders and CNS Modulation

作者: Kargbo, Robert B.

This Patent Highlight delves into the potential of next-generation therapeutics for treating mental disorders and modulating the central nervous system (CNS). Among the serotonin receptor subtypes, 5-HT2A, 5-HT2C, 5-HT1A, and 5-HT1B have shown promise in CNS disorder treatment. Approved drugs targeting these receptors, such as antipsychotics and psychedelics, provide valuable insights into their therapeutic effects. However, modulation of these receptors can lead to side effects like hallucinations and altered perception. The development of 5-HT2A agonists with minimized mood changes and improved therapeutic benefits is crucial. Furthermore, exploring morphic salt mixtures and specified salts offers innovative approaches to effectively modulating CNS activity and treating mental disorders.

2023-03-01·European Archives of Psychiatry and Clinical Neuroscience

Elevated levels of serotonin 5-HT2A receptors in the orbitofrontal cortex of antisocial individuals

Article

作者: Braccagni, Giulia ; Scheggi, Simona ; Bortolato, Marco

Antisocial behavior (ASB) is characterized by frequent violations of the rights and properties of others, as well as aggressive conduct. While ample evidence points to a critical role of serotonin in the emotional modulation of social responses, the implication of this neurotransmitter in ASB is unclear. Here, we performed the first-ever postmortem analysis of serotonergic markers in the orbitofrontal cortex (OFC) of male subjects with ASB (n = 9). We focused on this brain region, given its well-recognized role in social response and ASB pathophysiology. Given that all individuals also had a substance use disorder (SUD) diagnosis, two age-matched control groups were used: SUD only and unaffected controls. Tissues were processed for immunoblotting analyses on eight key serotonergic targets: tryptophan hydroxylase 2 (TPH2), the rate-limiting enzyme of brain serotonin synthesis; serotonin transporter (SERT), the primary carrier for serotonin uptake; monoamine oxidase A (MAOA), the primary enzyme for serotonin catabolism; and five serotonin receptors previously shown to influence social behavior: 5-HT_1A, 5-HT_1B, 5-HT_2A, 5-HT_2C, and 5-HT₄. Our analyses documented a significant increase in 5-HT_2A receptor levels in the ASB + SUD group compared to SUD-only controls. Furthermore, TPH2 levels were significantly reduced in the SUD group (including SUD only and ASB + SUD) compared to unaffected controls. No difference was detected in the expression of any other serotonergic target. These results are in keeping with previous evidence showing high 5-HT_2A receptor binding in the OFC of pathologically aggressive individuals and point to this molecule as a potential target for ASB treatment.

2023-01-01·Frontiers in oncology

Integrative dissection of 5-hydroxytryptamine receptors-related signature in the prognosis and immune microenvironment of breast cancer.

Article

作者: Pan, Bo ; Wang, Zhiyu ; Yang, Bowen ; Zheng, Yifeng ; Wang, Neng ; Wang, Xuan ; Zhan, Dandan ; Wang, Shengqi

BackgroundDepression increases the risk of breast cancer recurrence and metastasis. However, there lacks potential biomarkers for predicting prognosis in breast cancer. 5-hydroxytryptamine (5-HT) plays a key role in the pathogenesis and treatment of depression. In this study, we developed a prognostic signature based on 5-HT receptors (5-HTRs) and elucidated its potential immune regulatory mechanisms for breast cancer prognosis.MethodsOncomine, GEPIA, UALCAN, cBioPortal, Kaplan-Meier plotter, and TIMER were used to analyze differential expression, prognostic value, genetic alteration, and immune cell infiltration of HTRs in breast cancer patients. The model training and validation assays were based on the analyses of GSE1456 and GSE86166. A risk signature was established by univariate and multivariate Cox regression analyses. The transwell assay was utilized to verify the effect of the 5-HTRs expression on breast cancer invasion. Effects of HTR2A/2B inhibitor on CD8⁺ T cell proliferation and infiltration as well as apoptosis of 4T1 cells in the tumor microenvironment were detected by flow cytometry and TUNEL assay. Zebrafish and mouse breast cancer xenografts were used to determine the effect of HTR2A/2B inhibitor on breast cancer metastasis.ResultsThe expression levels of HTR1A, HTR1B, HTR2A, HTR2B, HTR2C, HTR4, and HTR7 were significantly downregulated in highly malignant breast cancer types. 5-HTRs were significantly associated with recurrence-free survival (RFS) in breast cancer patients. The genetic alteration of HTR1D, HTR3A, HTR3B, and HTR6 in breast cancer patients was significantly associated with shorter overall survival (OS). Finally, HTR2A and HTR2B were determined to construct the risk signature. The expression of HTR2A/2B was positively correlated with the infiltration of immune cells such as CD8⁺ T cells and macrophages. Furthermore, inhibition of HTR2A expression could suppress CD8⁺ T cell proliferation and enhance invasion and metastasis of breast cancer cells in both zebrafish and mice model.ConclusionsThe HTR2A/2B risk signature not only highlights the significance of HTRs in breast cancer prognosis by modulating cancer immune microenvironment, but also provides a novel gene-testing tool for early prevention of depression in breast cancer patients and lead to an improved prognosis and quality of life.