GTS-21 (also known as DMXBA or DMBX-anabaseine) is an

investigational new drug The United States Food and Drug Administration's Investigational New Drug (IND) program is the means by which a pharmaceutical industry, pharmaceutical company obtains permission to start human clinical trials and to ship an experimental drug inte ...

being studied for the treatment of

neurodegenerative disease A neurodegenerative disease is caused by the progressive loss of neurons, in the process known as neurodegeneration. Neuronal damage may also ultimately result in their death. Neurodegenerative diseases include amyotrophic lateral sclerosis, mul ...

s and

psychiatric disorder A mental disorder, also referred to as a mental illness, a mental health condition, or a psychiatric disability, is a behavioral or mental pattern that causes significant distress or impairment of personal functioning. A mental disorder is ...

s, as well as for its potential to enhance memory and cognitive function. It is a derivative of the

natural product A natural product is a natural compound or substance produced by a living organism—that is, found in nature. In the broadest sense, natural products include any substance produced by life. Natural products can also be prepared by chemical s ...

anabaseine Anabaseine (3,4,5,6-tetrahydro-2,3′-bipyridine) is an alkaloid toxin produced by ''Nemertines'' worms and ''Aphaenogaster'' ants. It is structurally similar to nicotine and anabasine. Similarly, it has been shown to act as an agonist on most ni ...

that acts as a

partial agonist In pharmacology, partial agonists are drugs that bind to and activate a given Receptor (biochemistry), receptor, but have only partial Intrinsic activity, efficacy at the receptor relative to a full agonist. They may also be considered Ligand (bio ...

at neural

nicotinic acetylcholine receptor Nicotinic acetylcholine receptors, or nAChRs, are Receptor (biochemistry), receptor polypeptides that respond to the neurotransmitter acetylcholine. Nicotinic receptors also respond to drugs such as the agonist nicotine. They are found in the c ...

s (nAChRs). It binds to both the

α4β2 The alpha-4 beta-2 nicotinic receptor, also known as the α4β2 receptor, is a type of nicotinic acetylcholine receptor implicated in learning, consisting of α4 and β2 subunits. It is located in the brain, where activation yields post- and pr ...

and α7

subtypes In programming language theory, subtyping (also called subtype polymorphism or inclusion polymorphism) is a form of type polymorphism. A ''subtype'' is a datatype that is related to another datatype (the ''supertype'') by some notion of substit ...

, but activates only the α7 to any significant extent. 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 display

nootropic Nootropics ( or ) (colloquially brain supplements, smart drugs, cognitive enhancers, memory enhancers, or brain boosters) are chemical substances which purportedly improve cognitive functions, such as attention, memory, wakefulness, and self ...

and

neuroprotective Neuroprotection refers to the relative preservation of neuronal structure and/or function. In the case of an ongoing insult (a neurodegenerative insult) the relative preservation of neuronal integrity implies a reduction in the rate of neuronal l ...

effects, and GTS-21 is being investigated for the treatment of

Alzheimer's disease Alzheimer's disease (AD) is a neurodegenerative disease and the cause of 60–70% of cases of dementia. The most common early symptom is difficulty in remembering recent events. As the disease advances, symptoms can include problems wit ...

, nicotine dependence, and, most significantly, for

schizophrenia Schizophrenia () is a mental disorder characterized variously by hallucinations (typically, Auditory hallucination#Schizophrenia, hearing voices), delusions, thought disorder, disorganized thinking and behavior, and Reduced affect display, f ...

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

Clinical trials

Phase one of a clinical trial using DXMBA as a potential treatment for schizophrenia was completed in January of 2005. This clinical trial was discontinued during phase II. Several other trials focusing on a range of health issues including Alzheimer's, schizophrenia, autism, ADHD, and nicotine use were either discontinued or withdrawn. Another study of GTS-21 in healthy volunteers found that the drug improved attention and memory performance.

History

The laboratory name GTS-21 means that it is the 21st chemical compound created by Gainesville (

University of Florida The University of Florida (Florida or UF) is a public university, public land-grant university, land-grant research university in Gainesville, Florida, United States. It is a senior member of the State University System of Florida and a preem ...

in Gainesville) and Tokushima (

Taiho Pharmaceutical is a Japanese pharmaceutical company, and a subsidiary of Otsuka Holdings, which focuses on developing cancer treatments. Taiho, headquartered in Tokyo, Japan, is an R&D-driven specialty pharma focusing on the three fields of oncology, allerg ...

) Scientists. DMXBA – 3-2,4-dimethoxybenzylidene anabaseine.

Animal studies

Clinical trials

History

References

Further reading