Delving into the Latest Updates on Anisodamine Hydrobromide with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms-

Target

mAChRs

Mechanism

mAChRs antagonists(Muscarinic acetylcholine receptor antagonists)

Therapeutic Areas

Infectious DiseasesNervous System DiseasesDigestive System Disorders+ [2]

Active Indication

GastrospasmShock, SepticVertigo

Inactive Indication-

Originator Organization

Chengdu First Pharmaceutical Co. Ltd.

Active Organization

Yichang Humanwell Pharmaceuticals Co., Ltd.

Tianjin Jinyao Pharmaceutical Co., Ltd.

Chengdu First Pharmaceutical Co. Ltd.

Inactive Organization-

Drug Highest PhaseApproved

First Approval Date

CN (01 Jan 1981),

GastrospasmShock, SepticVertigo

Regulation-

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Structure

Molecular FormulaC17H23NO4

InChIKeyWTQYWNWRJNXDEG-RBZJEDDUSA-N

CAS Registry55869-99-3

View All Structures (2)

Sepsis-induced myocardial dysfunction presents significant challenges in clinical management and is associated with increased mortality. Anisodamine (654-1/-2) has potentials in alleviating cardiac and endothelial impairments associated with sepsis. Exosomes, small vesicles secreted by cells, carry various bioactive molecules, such as nucleic acids, proteins, and lipids. These vesicles can travel to target cells to influence their function and modulating biological processes. In the context of endothelial-cardiac crosstalk, exosomes derived from endothelial cells can transfer signals that either exacerbate or mitigate myocardial injury, playing a crucial role in the progression of cardiovascular diseases. However, the precise role of endothelial-cardiac crosstalk, particularly through exosomes, in mediating the cardioprotective effects of anisodamine remains unclear. This study evaluated the effects of anisodamine on myocardial and endothelial injuries induced by LPS. Mechanisms were analyzed through network pharmacology, molecular docking, Western blotting, and RT-qPCR. The interaction between endothelial and cardiomyocyte inflammatory responses to anisodamine was assessed using a co-culture assay. Furthermore, both in vivo and in vitro assays were conducted to evaluate the effects of anisodamine-/LPS- treated HUVECs exosomes on A16 cell and myocardial function in mice. Anisodamine effectively mitigated apoptosis, inflammation, mitochondrial and myocardial injury, glycocalyx degradation, and oxidative stress by regulating the PI3K-AKT, NLRP-3/Caspase-1/ASC, TNF-α/PKCα/eNOs/NO, and NF-κB/iNOs/NO pathways in A16 cells and HUVECs. Moreover, in vivo and in vitro assays confirmed the protective effects of anisodamine against myocardial injuries mediated by exosomes derived from LPS-treated HUVECs. In summary, anisodamine ameliorated inflammation-induced endothelial and cardiomyocyte dysfunction. The in vitro and in vivo assays demonstrated that anisodamine could alleviate myocardial dysfunction through exosome-mediated mechanisms, offering new therapeutic avenues for treating myocardial injury and highlighting the potential of targeted exosome therapy in clinical settings.

16 Sep 2024·Bioanalysis

Comparative pharmacokinetic study of Anisodamine Hydrobromide tablets and injection in septic acute lung injury rats

Article

Author: Wu, Rui ; Zhang, Jianlan ; Dai, Shu ; Yu, Yujie ; Nan, Feng ; Liu, Yanfang ; Li, Yunxia ; Zhang, Fang ; Yao, Chenhao ; Wan, Feng

Aim: We aimed to establish a sensitive LC-MS/MS method to analyze the pharmacokinetics of Ani HBr tablets and injection.Methods: Around 10 mmNH₄Ac containing 0.1% formic acid and acetonitrile were used as the mobile phase. Acute lung injury in septic and normal rats, respectively, were administered Ani HBr tablets at doses of 12.5, 25 and 50 mg/kg and injection at doses of 4, 8 and 16 mg/kg, followed by extraction of the drugs from plasma using ethyl acetate for subsequent analysis.Results & conclusion: The method met the requirements for biological analysis. Ani HBr tablets absorbed slowly in rats with disease, tail vein administration was a more promising approach for treating septic acute lung injury.

02 Sep 2024·Immunopharmacology and Immunotoxicology

Anisodamine hydrobromide ameliorates acute lung injury via inhibiting pyroptosis in murine sepsis model

Article

Author: Xiao, Yuanyuan ; Xiong, Shiqiang ; Xiang, Tao ; Zhang, Bihua ; Luo, Li ; Zhang, Ting

OBJECTIVESepsis can have severe implications on lung function, leading to acute lung injury (ALI), a major contributor to sepsis-related mortality. Anisodamine hydrobromide (Ani HBr), a bioactive constituent derived from the root of Scopolia tangutica Maxim, a plant endemic to China, has demonstrated efficacy in treating septic shock. We aim to explore whether Ani HBr can alleviate sepsis-triggered acute lung injury (ALI) and elucidate the fundamental mechanisms involved.MATERIALS AND METHODThe protective effects of Ani HBr were assessed in two models: in vitro, lipopolysaccharide (LPS)-stimulated RAW264.7 cells, and in vivo, cecal ligation puncture (CLP)-induced sepsis. To measure the cell viability of RAW264.7 cells after Ani HBr treatment, we used the CCK-8 assay. We quantified the levels of pro-inflammatory cytokines expression using ELISA. We also measured the expression of pyrotosis indicators by quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR), Western blotting, and immunofluorescence.RESULTSOur study demonstrates that Ani HBr can alleviate pulmonary edema, bleeding, and excessive inflammation induced by CLP. Additionally, it exhibits protective effects against cytotoxicity induced by LPS in RAW264.7 macrophage cells. Furthermore, Ani HBr downregulates the mRNA and protein levels of NLRP3, Caspase-1, GSDMD, IL-18, and IL-1β in both animal models and cell cultures, thereby inhibiting pyroptosis in a similar mechanism to AC-YVAD-CMK (AYC)'s blockade of Caspase-1. Moreover, Ani HBr suppresses the production and release of proinflammatory cytokines.CONCLUSIONThese findings suggest that Ani HBr could serve as a protective agent against sepsis-induced ALI by suppressing pyroptosis.

100 Deals associated with Anisodamine Hydrobromide

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External Link

KEGG	Wiki	ATC	Drug Bank
-	Anisodamine Hydrobromide	V	DB11785

R&D Status

10 top approved records.

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Indication	Country/Location	Organization	Date
Gastrospasm	CN	Chengdu First Pharmaceutical Co. Ltd.	01 Jan 1981
Gastrospasm	CN	Tianjin Jinyao Pharmaceutical Co., Ltd.	01 Jan 1981
Gastrospasm	CN	Yichang Humanwell Pharmaceuticals Co., Ltd.	01 Jan 1981
Shock, Septic	CN	Chengdu First Pharmaceutical Co. Ltd.	01 Jan 1981
Vertigo	CN	Chengdu First Pharmaceutical Co. Ltd.	01 Jan 1981
Vertigo	CN	Yichang Humanwell Pharmaceuticals Co., Ltd.	01 Jan 1981
Vertigo	CN	Tianjin Jinyao Pharmaceutical Co., Ltd.	01 Jan 1981

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT02442440 (Pubmed \| Crit Care)	Phase 1/2	Shock, Septic	469	anisodamine (Usual care)	fgaiwunfzi(szfwdtkwif): OR = 0.84 (95% CI, 0.5 - 0.93)	Negative	27 Sep 2021
				Anisodamine