This is a sequential multiple assignment randomized trial for adults (ages > 18) with a bipolar disorder type 1 diagnosis currently experiencing a depressive episode. It is a randomized pragmatic trial that will compare four commonly prescribed treatments for bipolar depression, which includes three FDA-approved medications (Cariprazine, Quetiapine and Lurasidone) and one antipsychotic/antidepressant combination (Aripiprazole/Escitalopram).

Start Date01 Sep 2024

Sponsor / Collaborator

The General Hospital Corp.

[+1]

100 Clinical Results associated with SERT x D2 receptor

100 Translational Medicine associated with SERT x D2 receptor

0 Patents (Medical) associated with SERT x D2 receptor

167

Literatures (Medical) associated with SERT x D2 receptor

01 Nov 2024·Phytomedicine

Network pharmacology screening, in vitro and in vivo evaluation of antianxiety and antidepressant drug-food analogue

Article

Author: Luo, Ting ; Xu, Zi-yang ; Wu, Min-rui ; Li, Long-Jie ; Xu, Zi-Yang ; Zhao, Zhi-Heng ; Zhao, Zhi-heng ; Ren, Xiao-yu ; Wang, Li-Mei ; Ren, Xiao-Yu ; Wu, Min-Rui ; Wang, Hong-Xun ; Wang, Li-mei ; Wang, Hong-xun ; Li, Long-jie ; Yi, Yang

BACKGROUNDDepression and anxiety disorders are prevalent psychiatric conditions, and currently utilized chemical drugs typically come with significant adverse effects. China boasts a wealth of medicinal and food herbs known for their safe and effective properties.PURPOSEThis study aimed to develop novel formulations with improved antidepressant and anxiolytic effects derived from medicinal and food herbs.STUDY DESIGNScreening combinations with antidepressant and anxiolytic effects using techniques such as network pharmacology and validating their effects in vitro and in vivo experiments.METHODSUtilizing network pharmacology and molecular docking, we identified the top ten medicinal herbs with anxiolytic and antidepressant potential. Herbs with cytoprotective effects and non-toxic characteristics were further screened to formulate the herbal blends. Subsequently, we established a PC12 cell injury model and a chronic unpredictable mild stress (CUMS) model in mice to assess the effects of our formulations.RESULTSTen medicinal herbs were initially screened, and six of them were deemed suitable for formulating the blend, namely Gancao, Dazao, Gouqizi, Sangye, Huangqi, and Jinyinhua (GDGSHJ). The GDGSHJ formulation reduced Lactate Dehydrogenase (LDH) leakage, decreased apoptosis, and demonstrated a favorable antidepressant and antianxiety effect in the CUMS mouse model. Besides, GDGSHJ led to the upregulation of serum 5-Hydroxytryptamine (5-HT) content and brain tissue 5-HT, Gamma-aminobutyric acid (GABA), and Dopamine (DA) levels. It also downregulated the expression of SLC6A4 and SLC6A3 genes in the mouse hippocampus while upregulating HTR1A, DRD1, DRD2, and GABRA1 genes.CONCLUSIONOur formulation exhibited robust antidepressant and antianxiety effects without inducing substantial toxicity. This efficacy appears to be mediated by the expression of relevant genes within the hippocampus of mice. The formulation achieved this effect by balancing 5-HT levels in the serum and DA, GABA, and 5-HT levels within brain tissue.

05 Jul 2024·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

Author: 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.

01 Apr 2024·Environmental Research

Dopaminergic and serotoninergic systems as preferential targets of the pyrethroid tefluthrin exposure in the rat brain

Article

Author: Ares, Irma ; Martínez, Marta ; Martínez-Larrañaga, María-Rosa ; Anadón, Arturo ; Lopez-Torres, Bernardo ; Maximiliano, Jorge-Enrique ; Martínez, María-Aránzazu

The monoaminergic systems dopamine (DA) and serotonin (5-HT) play important roles in neuromodulation, such as motor control, cognitive, affective, and neuroendocrine functions. In the present research study, we addressed the hypothesis that exposure to Type I pyrethroid tefluthrin may specifically target the dopaminergic and serotoninergic systems. Tefluthrin could modify brain monoamine neurotransmitters, DA and 5-HT levels as well as dopaminergic and serotoninergic signaling pathways. Adult male Wistar rats were treated with tefluthrin [2.2, 4.4 and 5.5 mg/kg bw, equivalent to 1/10, 1/5 and 1/4 of the acute oral rat lethal dose 50 (LD₅₀) value] by oral gavage, six days. After last dose of tefluthrin, DA and 5-HT and metabolites levels were determined in brain regions (striatum, hippocampus, prefrontal cortex and hypothalamus). Tefluthrin induced a decrease of DA, 5-HT and metabolites contents, in a brain regional- and dose-related manner. The major decreases in DA and 5-HT contents were observed in prefrontal cortex tissue. Here, we studied that in vivo exposure to tefluthrin may alter DA and 5-HT neurotransmission in prefrontal cortex. Transcripts related to (i) dopaminergic [dopamine transporter 1 (Dat1), tyrosine hydroxylase (TH), dopamine receptors (Drd1, Drd2)], (ii) serotoninergic [serotonin transporter (SERT), tryptophan hydroxylase 2 (TPH2), serotonin receptors (5-HT1A, 5-HT2A)] and (iii) DA and 5-HT degradation [monoamine oxidases (MAOA, MAOB)] signaling pathways were investigated. Results showed that tefluthrin induced down-regulation of transcripts responsible for the synthesis and action of DA (TH, Drd1, Drd2) and 5-HT (SERT, TPH2). In contrast, tefluthrin treatment induced up-regulation of genes involved in DA transporter (Dat1), 5-HT receptors (5-HT1A, 5-HT2A) and monoamine oxidases (MAOA, MAOB). Given the integral roles of mitochondrial dysfunction and dopaminergic and serotoninergic alterations as hallmarks of neurodegenerative diseases, our data suggest that tefluthrin may be a candidate for pesticides contributing to neurodegenerative disorders pathogenesis by causing damage to the DA and 5-HT systems.

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