GTS-21

GTS-21 (also known as DMXBA or DMBX-anabaseine) is an investigational new drug being studied for the treatment of neurodegenerative diseases and psychiatric disorders, as well as for its potential to enhance memory and cognitive function.

GTS-21

Clinical data
Other names	3-(2,4-dimethoxy-benzylidene)anabaseine
Identifiers
IUPAC name (3E)-3-(2,4-Dimethoxybenzylidene)-3,4,5,6-tetrahydro-2,3'-bipyridine
CAS Number	148372-04-7
PubChem CID	5310985
ChemSpider	4470526
UNII	8S399XDN2K
CompTox Dashboard (EPA)	DTXSID701027513
Chemical and physical data
Formula	C19H20N2O2
Molar mass	308.381 g·mol−1
3D model (JSmol)	Interactive image
SMILES COc2cc(OC)ccc2C=C1CCCN=C1c3cnccc3
InChI InChI=1S/C19H20N2O2/c1-22-17-8-7-14(18(12-17)23-2)11-15-5-4-10-21-19(15)16-6-3-9-20-13-16/h3,6-9,11-13H,4-5,10H2,1-2H3/b15-11+ Key:RPYWXZCFYPVCNQ-RVDMUPIBSA-N
(verify)

It is a derivative of the natural product anabaseine that acts as a partial agonist at neural nicotinic acetylcholine receptors (nAChRs). It binds to both the α4β2 and α7 subtypes, but activates only the α7 to any significant extent.^[1][2] Activation of the α7 nAChR has been shown to have neuroprotective effects and to improve cognitive function, making it an attractive target for drug development.

Both GTS-21 itself and its demethylated active metabolite 4-OH-GTS-21^[3] display nootropic^[4] and neuroprotective effects,^[5][6][7][8] and GTS-21 is being investigated for the treatment of Alzheimer's disease,^[9][10] nicotine dependence,^[11] and, most significantly, for schizophrenia.^{[12][13][14][15][16]}

Animal studies

Several studies have investigated the effects of GTS-21 in various animal models of neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, and multiple sclerosis. In these studies, GTS-21 has been shown to have anti-inflammatory and neuroprotective effects, and to improve cognitive function.

A recent study investigated the cholinergic anti-inflammatory pathway (CAP) in rheumatoid arthritis (RA). They used the α7 nicotinic acetylcholine receptor (α7nAChR) agonist GTS-21 to study its role in reducing synovial inflammation in a mice model of collagen-induced arthritis (CIA). GTS-21 lessened inflammation and reduced monocyte infiltration into the synovium. This study highlights a new mechanism by which cholinergic signaling can mitigate synovial inflammation in RA.^[17]

GTS-21 reduces the occurrence of atrial fibrillation in septic mice by modulating macrophage activity.^[18]

Clinical trials

Phase one of a clinical trial using DXMBA as a potential treatment for schizophrenia was completed in January of 2005.^[19] This clinical trial was discontinued during phase II.^[19] Several other trials focusing on a range of health issues including Alzheimer's, schizophrenia, autism, ADHD, and nicotine use were either discontinued or withdrawn.^{[20][21][22][23][24]}

Another study of GTS-21 in healthy volunteers found that the drug improved attention and memory performance.^[4]

History

The laboratory name GTS-21 means that it is the 21st chemical compound created by Gainesville (University of Florida in Gainesville) and Tokushima (Taiho Pharmaceutical) Scientists.^[25] DMXBA – 3-2,4-dimethoxybenzylidene anabaseine.