Delving into the Latest Updates on DMXB-Anabaseine with Synapse

Overview

Basic Info

Drug Type

Small molecule drug

Synonyms

3-(2,4-dimethoxybenzylidene)anabaseine, 3-2,4 dimethoxy-benzilidene anabaseine, DMXB-A

+ [4]

Target

CHRNA7

Mechanism

α7 receptor agonists(Neuronal acetylcholine receptor protein alpha-7 subunit agonists)

Therapeutic Areas

Nervous System DiseasesOther Diseases

Active Indication-

Inactive Indication

Alzheimer DiseaseAttention Deficit Disorder With HyperactivityAutistic Disorder+ [2]

Originator Organization

CoMentis, Inc.

Active Organization-

Inactive Organization

CoMentis, Inc.

The University of Colorado

University of Colorado Denver

Drug Highest PhaseDiscontinuedPhase 2

First Approval Date-

Regulation-

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Structure

Molecular FormulaC19H22Cl2N2O2

InChIKeyBXKYFUGAAFLYJL-BXGYHSFXSA-N

CAS Registry156223-05-1

View All Structures (2)

Attempts to quit cigarette smoking are often accompanied by negative mood and problems in attention and memory. These effects, in turn, may contribute to smoking relapse. This exploratory/developmental project examines the effects of a novel medication, GTS-21, on individuals interested in smoking cessation. It is hypothesized that GTS-21 will reduce negative affect, improve cognition and/or reduce smoking relapse in healthy adult men and women who are chronic cigarette smokers.

Start Date29 Sep 2018

Sponsor / Collaborator

University of Florida

[+1]

NCT02458313 / CompletedPhase 1IIT

Nicotinic Agonist Effects on BMI and Neuronal Response in Overweight/Obese Adults

Obesity is a serious and growing health problem in the United States. Obesity is associated with health problems such as type-2 diabetes and cardiovascular disease, leading to decreased quality of life and increased mortality. Given the health and quality-of-life effects of obesity, developing effective treatments clearly is an important goal.
This study plans to learn more about the effects of an investigational new drug (DMXB-A (3-(2,4-dimethoxybenzylidene anabaseine)) and its effects on obesity. The study drug has similar effects to nicotine. Since nicotine has been found to affect appetite, the investigators are interested in studying effects of the study drug, which has some similarities to nicotine, on how your brain responds to such things as pictures of food. The study drug has not been approved by the Food and Drug Administration (FDA), and is considered experimental.

Start Date14 Apr 2016

Sponsor / Collaborator

University of Colorado Denver

NCT02538081 / WithdrawnPhase 1/2IIT

Nicotinic Receptors and Schizophrenia

This study proposes to conduct a clinical trial comparison of olanzapine and the combination of a nicotinic cholinergic agonist, 3-[2,4-Dimethoxybenzylidene]anabaseine (DMXB-A) with a dopamine D2 receptor antagonist, the mechanism common to all antipsychotic drugs, to test the hypothesis that 7-nicotinic receptor agonism may be an additional necessary factor that enhances the efficacy of olanzapine that allows its slight superiority to risperidone. This trial would enroll patients taking olanzapine and record baseline measurements of clinical symptoms, cognition, metabolic parameters, and extrapyramidal side effects. The subjects would then be randomized to receive either risperidone or risperidone plus DMXB-A for 6 weeks and then would again have measurements of clinical symptoms, cognition, metabolic parameters and extrapyramidal side effects.

Start Date01 Aug 2015

Sponsor / Collaborator

VA Office of Research and Development

[+1]

100 Clinical Results associated with DMXB-Anabaseine

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100 Translational Medicine associated with DMXB-Anabaseine

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100 Patents (Medical) associated with DMXB-Anabaseine

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243

Literatures (Medical) associated with DMXB-Anabaseine

01 Sep 2024·International Immunopharmacology

Activation of the α7nAChR by GTS-21 mitigates septic tubular cell injury and modulates macrophage infiltration

Article

Author: Umene, Ryusuke ; Nakamura, Yasuna ; Matsuo, Sayumi ; Wu, Chia-Hsien ; Inoue, Tsuyoshi ; Yang, Aobing

The most common and serious complication among hospitalized and critically ill patients is sepsis-associated acute kidney damage (S-AKI), which raises the risk of comorbidities and is linked to a high mortality rate. Cholinergic anti-inflammatory pathway (CAP), an anti-inflammatory pathway mediated by the vagus nerve, acetylcholine, and α7 nicotinic acetylcholine receptors (α7nAChRs), offers new perspectives for the treatment of S-AKI. In this study, we investigated the role of CAP and α7nAChR in kidney injury by employing an LPS-induced septic kidney injury mouse model and GTS-21 intervention. C57BL/6 mice were injected with LPS, with or without GTS-21, in different subgroups. Kidney function was assessed by plasma creatinine, histology, and markers of kidney injury 24 h after intervention. The results demonstrated that GTS-21 could inhibit the systemic inflammatory response and directly protect the tubular cell injury from LPS. To explore the novel gene involved in this response, RNA sequencing of the renal proximal tubular epithelial cell (HK-2), pretreated with LPS and GTS-21, was conducted. The results indicate that GTS-21 administration reduces LPS-induced cytokines and chemokines secretion by HK-2, including CCL20, a potent chemokine attracting monocytes/macrophages. Furthermore, a macrophage transmigration assay revealed that GTS-21 inhibits macrophage transmigration by downregulating the expression of CCL20 in HK-2 cells. In conclusion, GTS-21, as an α7nAChR agonist, emerges as a noteworthy and versatile treatment for S-AKI. Its dual function of directly protecting renal tubular cells and regulating inflammatory responses represents a major advancement in the treatment of sepsis-induced AKI. This finding might pave the way for novel approaches to improving patient outcomes and reducing death rates in sepsis-related complications.

01 May 2024·International Immunopharmacology

Corrigendum to “GTS-21 attenuates ACE/ACE2 ratio and glycocalyx shedding in lipopolysaccharide-induced acute lung injury by targeting macrophage polarization derived ADAM-17” [Int. Immunopharmacol. 129 (2024) 111603]

Author: Hu, Chang ; Hu, Bo ; Wang, Fengyun ; Wang, Xiaozhi ; Zhang, Dandan ; Zhao, Qiuyue ; Li, Jianguo ; Zhu, Weiwei

01 Mar 2024·International Immunopharmacology

GTS-21 attenuates ACE/ACE2 ratio and glycocalyx shedding in lipopolysaccharide-induced acute lung injury by targeting macrophage polarization derived ADAM-17

Article

Author: Hu, Chang ; Hu, Bo ; Wang, Fengyun ; Wang, Xiaozhi ; Zhang, Dandan ; Zhao, Qiuyue ; Li, Jianguo ; Zhu, Weiwei

Acute lung injury (ALI) has received considerable attention in intensive care owing to its high mortality rate. It has been demonstrated that the selective alpha7 nicotinic acetylcholine receptor agonist Gainesville Tokushima scientists (GTS)-21 is promising for treating ALI caused by lipopolysaccharides (LPS). However, the precise underlying mechanism remains unknown. This study aimed to investigate the potential efficacy of GTS-21 in the treatment of ALI. We developed mouse models of ALI and alveolar epithelial type II cells (AT2s) injury following treatment with LPS and different polarized macrophage supernatants, respectively. Pathological changes, pulmonary edema, and lung compliance were assessed. Inflammatory cells count, protein content, and pro-inflammatory cytokine levels were analysed in the bronchoalveolar lavage fluid. The expression of angiotensin-converting enzyme (ACE), ACE2, syndecan-1 (SDC-1), heparan sulphate (HS), heparanase (HPA), exostosin (EXT)-1, and NF-κB were tested in lung tissues and cells. GTS-21-induced changes in macrophage polarization were verified in vivo and in vitro. Polarized macrophage supernatants with or without recombination a disintegrin and metalloproteinase-17 (ADAM-17) and small interfering (si)RNA ADAM-17 were used to verify the role of ADAM-17 in AT2 injury. By reducing pathological alterations, lung permeability, inflammatory response, ACE/ACE2 ratio, and glycocalyx shedding, as well as by downregulating the HPA and NF-κB pathways and upregulating EXT1 expression in vivo, GTS-21 significantly diminished LPS-induced ALI compared to that of the LPS group. GTS-21 significantly attenuated macrophage M1 polarization and augmented M2 polarization in vitro and in vivo. The destructive effects of M1 polarization supernatant can be inhibited by GTS-21 and siRNA ADAM-17. GTS-21 exerted a protective effect against LPS-induced ALI, which was reversed by recombinant ADAM-17. Collectively, GTS-21 alleviates LPS-induced ALI by attenuating AT2s ACE/ACE2 ratio and glycocalyx shedding through the inhibition of macrophage M1 polarization derived ADAM-17.

100 Deals associated with DMXB-Anabaseine

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External Link

KEGG	Wiki	ATC	Drug Bank
-	-	-	DB05708

R&D Status

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Attention Deficit Disorder With Hyperactivity	Phase 2	US	CoMentis, Inc.	01 Feb 2007
Schizophrenia	Phase 2	US	University of Colorado Denver	01 Jan 2005
Alzheimer Disease	Phase 2	-	The University of Colorado	-
Alzheimer Disease	Phase 2	-	The University of Colorado	-
Autistic Disorder	Phase 2	-	CoMentis, Inc.	-
Autistic Disorder	Phase 2	-	The University of Colorado	-
Cognition Disorders	Phase 2	-	The University of Colorado	-
Cognition Disorders	Phase 2	US	CoMentis, Inc.	-

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Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT02458313 (CTgov)	Phase 1	Obesity	61	DMXB-A (DMXB-A)	whwtprtkqd(xiimpbeoml) = etrwgtdmhl tgcszfsxzd (xmiprnrzfp, mgpxwjlroe - hbdkakaiiu) View more	-	12 Jun 2023
				Placebo (Placebo)	whwtprtkqd(xiimpbeoml) = yjslqprmon tgcszfsxzd (xmiprnrzfp, wyikhdhcmf - hbbseavmjs) View more
NCT00100165 (DMXB-A, CTgov)	Phase 2	Schizophrenia	29	Placebo	mbfeqcmjrq(pkfdnhejay) = wqygglquck zahqhqgomt (kzdsgjnqqi, rnkkkorssw - vhkyjygcdj) View more	-	29 Jan 2020
NCT01400477 (CTgov)	Phase 2	Schizoaffective disorder \| Schizophrenia	97	DMXB-A-SR (DMXB-A-SR)	djdrzeanuw(dcjoqobglj) = zwzrfcoyzk tqvcnwocpb (lkkrfnnvnc, hxeqhfgsrv - qnelmdqsjx) View more	-	07 May 2019
				Placebo (Arm #2: Placebo Comparator)	djdrzeanuw(dcjoqobglj) = xqtzahnvve tqvcnwocpb (lkkrfnnvnc, ukhdncwqak - xdgvykraep) View more
UEGW	Not Applicable	Colitis	-	GTS-21 treatment control group	sljqapmufg(xvgxupuyhy) = tfunibdgmr hbbutkymii (odrwiykesp ) View more	-	01 Oct 2017
				GTS-21 (Î±-BGT group)	xnpxmqhtpw(nrwmkhlcdu) = nxdoxucwlz xroropvzcz (zrywstdxjn )