更新于：2024-11-01

5-HT3A receptor x NK1R

更新于：2024-11-01

基本信息

关联

项与 5-HT3A receptor x NK1R 相关的药物

HR-20013

靶点

5-HT3A receptor x NK1R

作用机制

5-HT3A receptor拮抗剂 [+1]

在研机构

福建盛迪医药有限公司

原研机构

福建盛迪医药有限公司

在研适应症

化疗引起的恶心和呕吐 [+4]

非在研适应症-

最高研发阶段申请上市

首次获批国家/地区-

首次获批日期1800-01-20

项与 5-HT3A receptor x NK1R 相关的临床试验

CTR20243064 / Recruiting临床3期

以盐酸帕洛诺司琼为对照，评价注射用HR20013用于预防中致吐风险抗肿瘤药物引起恶心呕吐的有效性和安全性研究—多中心、随机、双盲双模拟、阳性对照Ⅲ期临床研究

评价注射用HR20013用于预防中致吐风险抗肿瘤药物引起恶心呕吐的有效性；评价注射用HR20013用于预防中致吐风险抗肿瘤药物引起恶心呕吐的安全性和HR20013的群体药代动力学特征

开始日期2024-09-03

申办/合作机构

福建盛迪医药有限公司

NCT06554184 / Recruiting临床3期

A Randomized Phase III Study Evaluating the Efficacy and Safety of HR20013 for Nausea and Vomiting Associated With Moderate Emetic Risk Anticancer Agents

This study is aimed to evaluate the efficacy and safety of HR20013 versus palonosetron for nausea and vomiting associated with moderate emetic risk anticancer agents

开始日期2024-09-03

申办/合作机构

福建盛迪医药有限公司

100 项与 5-HT3A receptor x NK1R 相关的临床结果

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100 项与 5-HT3A receptor x NK1R 相关的转化医学

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0 项与 5-HT3A receptor x NK1R 相关的专利（医药）

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项与 5-HT3A receptor x NK1R 相关的文献（医药）

2024-03-01·European Journal of Pharmacology

Involvement of peripheral mast cells in a fibromyalgia model in mice

Article

作者: Fialho, Maria Fernanda Pessano ; Becker, Gabriela ; Oliveira, Sara Marchesan ; Brum, Evelyne da Silva ; Nogueira, Cristina Wayne

Fibromyalgia is a painful disorder of unknown aetiology that presents activation and recruitment of innate immune cells, including mast cells. Efforts have been made to understand its pathogenesis to manage it better. Thus, we explored the involvement of peripheral mast cells in an experimental model of fibromyalgia induced by reserpine. Reserpine (1 mg/kg) was subcutaneously (s.c.) injected once daily in the back of male Swiss mice for three consecutive days. We analysed mechanical and cold allodynia, muscle fatigue and number of mast cell in plantar tissue. The fibromyalgia induction produced mast cell infiltration (i.e., mastocytosis) in the mice's plantar tissue. The depletion of mast cell mediators with the compound 48/80 (0.5-4 mg/kg, intraperitoneal (i.p.)) or the mast cell membrane stabilizer ketotifen fumarate (10 mg/kg, oral route (p.o.) widely (80-90 %) and extensively (from 1 up to 10 days) prevented reserpine-induced mechanical and cold allodynia and muscle fatigue. Compound 48/80 also prevented the reserpine-induced mastocytosis. Finally, we demonstrated that PAR-2, 5-HT_2A, 5-HT₃, H₁, NK1 and MrgprB2 receptors, expressed in neuronal or mast cells, seem crucial to mediate fibromyalgia-related cardinal symptoms since antagonists or inhibitors of these receptors (gabexate (10 mg/kg, s.c.), ENMD-1068 (10 mg/kg, i.p.), ketanserin (1 mg/kg, i.p.), ondansetron (1 mg/kg, p.o.), promethazine (1 mg/kg, i.p.), and L733,060 (5 mg/kg, s.c.), respectively) transiently reversed the reserpine-induced allodynia and fatigue. The results indicate that mast cells mediate painful and fatigue behaviours in this fibromyalgia model, representing potential therapy targets to treat fibromyalgia syndrome.

2023-01-01·Frontiers in immunology

Combination of thalidomide and Clostridium butyricum relieves chemotherapy-induced nausea and vomiting via gut microbiota and vagus nerve activity modulation.

Article

作者: Wu, Heng ; Wei, Hong ; Wei, Jing ; Zhu, Ruizhe ; Shang, Gaishuang ; Tian, Puyuan ; Chen, Tingtao ; Shang, Haitao ; Zhao, Xuanqi

Nausea and vomiting (CINV) are distressful and widespread side effects of chemotherapy, and additional efficient regimens to alleviate CINV are urgently needed. In the present study, colorectal cancer (CRC) mice model induced by Azoxymethane (AOM)/Dextran Sodium Sulfate (DSS) was employed to evaluate the cancer suppression and CINV amelioration effect of the combination of thalidomide (THD) and Clostridium butyricum. Our results suggested that the combination of THD and C. butyricum abundantly enhanced the anticancer effect of cisplatin via activating the caspase-3 apoptosis pathway, and also ameliorated CINV via inhibiting the neurotransmitter (e.g., 5-HT and tachykinin 1) and its receptor (e.g., 5-HT₃R and NK-1R) in brain and colon. Additionally, the combination of THD and C. butyricum reversed the gut dysbacteriosis in CRC mice by increasing the abundance of Clostridium, Lactobacillus, Bifidobacterium, and Ruminococcus at the genus level, and also led to increased expression of occludin and Trek1 in the colon, while decreased expression of TLR4, MyD88, NF-κB, and HDAC1, as well as the mRNA level of IL-6, IL-1β, and TNF-α. In all, these results suggest that the combination of THD and C. butyricum had good efficacy in enhancing cancer treatments and ameliorating CINV, which thus provides a more effective strategy for the treatment of CRC.

2022-06-01·Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica

[Mechanism of Huanglian Houpo Decoction in treatment of ulcerative colitis in mice based on brain-gut axis].

Article

作者: Wang, Jia-Jun ; Wang, Li-Ying ; Yuan, Jian-Mei ; Ren, Mi-Hong ; Li, Yong ; Wang, Jian ; Li, Hong-Yan ; Gong, Dao-Yin

Based on the brain-gut axis, the present study investigated the effect of Huanglian Houpo Decoction(HLHPD) in the treatment of ulcerative colitis(UC) and explored the mechanism in the regulation of 5-hydroxytryptamine(5-HT), substance P(SP), and vasoactive intestinal peptide(VIP) using modern technologies and molecular docking. Sixty male C57 BL/6 J mice were randomly divided into a blank control group, a model group, a sulfasalazine(SASP) group, and high-(5.00 g·kg~(-1)), medium-(2.50 g·kg~(-1)), and low-dose(1.25 g·kg~(-1)) HLHPD groups. The UC model was induced by oral administration of water containing 3% dextran sulfate sodium salt(DSS) in mice except those in the blank control group. After HLHPD was administered for 10 days, the mice were sacrificed for sample collection. Morphological changes of colon tissues were observed by HE staining. The expression of 5-HT, SP, VIP, tumor necrosis factor α(TNF-α), interleukin-6(IL-6), and interleukin-1β(IL-1β) in the hypothalamus, serum, and colon was determined by the enzyme-linked immunosorbent assay(ELISA). The expression of tryptophan hydroxylase 1(TPH1), SP, and VIP in colon tissues was evaluated by immunohistochemistry. The expression of brain-gut peptide receptors, such as 5-HT3 A, neurokinin receptor 1(NK-1 R), and VIP receptor 1(VPAC1) in colon tissues was investigated by Western blot. The binding affinity of the brain-gut peptide receptors to the main components of HLHPD was analyzed by molecular docking. After HLHPD intervention, UC mice showed increased body weight, reduced DAI score and occult blood, prolonged colon, down-regulated levels of TNF-α, IL-1β, and IL-6 in colon tissues, and relieved pathological damage in the colon. The VIP levels in the colon were significantly up-regulated in the HLHPD groups. The high-and medium-dose HLHPD could significantly down-regulated SP and 5-HT in colon tissues and 5-HT in the serum, and up-regulated the VIP in the serum. The high-dose HLHPD group could down-regulate 5-HT and up-regulate VIP in the hypothalamus. It is suggested that HLHPD can reverse the levels of brain-gut peptides in UC mice to varying degrees. Correlation analysis results suggested that the expression levels of brain-gut peptides in the hypothalamus, serum, and colon tissues were related to inflammatory factors. Molecular docking results showed that berberine, coptisine, and epiberberine were presumedly the material basis for HLHPD in regulating the levels of 5-HT3 A, NK-1 R, and VPAC1. The main components of HLHPD may reduce colonic inflammation and pathological damage of colon tissues by regulating the activity of brain-gut peptides and their receptors, thereby reducing DSS-induced colitis in mice.