GTS-21 (DMXBA) 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 syn ...
anabaseine
Anabaseine (3,4,5,6-tetrahydro-2,3′-bipyridine) is an alkaloid toxin produced by '' Nemertines'' and ''Aphaenogaster'' ants. It is structurally similar to nicotine and anabasine. Similarly, it has been shown to act as an agonist on most nicotin ...
that acts as a
partial agonist
In pharmacology, partial agonists are drugs that bind to and activate a given receptor, but have only partial efficacy at the receptor relative to a full agonist. They may also be considered ligands which display both agonistic and antagonistic e ...
at neural
nicotinic acetylcholine receptor
Nicotinic acetylcholine receptors, or nAChRs, are receptor polypeptides that respond to the neurotransmitter acetylcholine. Nicotinic receptors also respond to drugs such as the agonist nicotine. They are found in the central and peripheral ne ...
s. It binds to both the
α4β2 and
α7 subtypes
In programming language theory, subtyping (also subtype polymorphism or inclusion polymorphism) is a form of type polymorphism in which a subtype is a datatype that is related to another datatype (the supertype) by some notion of substitutability, ...
, but activates only the α7 to any significant extent.
Both GTS-21 itself and its demethylated active metabolite 4-OH-GTS-21 display
nootropic
Nootropics ( , or ) (colloquial: smart drugs and cognitive enhancers, similar to adaptogens) are a wide range of natural or synthetic supplements or drugs and other substances that are claimed to improve cognitive function or to promote re ...
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 los ...
effects,
and GTS-21 is being investigated for the treatment of
Alzheimer's disease
Alzheimer's disease (AD) is a neurodegeneration, neurodegenerative disease that usually starts slowly and progressively worsens. It is the cause of 60–70% of cases of dementia. The most common early symptom is difficulty in short-term me ...
, nicotine dependence, and, most significantly, for
schizophrenia
Schizophrenia is a mental disorder characterized by continuous or relapsing episodes of psychosis. Major symptoms include hallucinations (typically hearing voices), delusions, and disorganized thinking. Other symptoms include social withdra ...
.
Phase one of a clinical trial using DXMBA as a potential treatment was completed in January of 2005. 12 non-smoking subjects each received 3 daily treatments. The treatments consisted of 150mg of DMXBA, with another dose of 75mg administered 2 hours later, 75mg of DXMBA, with another dose of 37.5mg administered 2 hours later, and a placebo treatment. The order of the doses was randomized over the 3-day course of the treatments. A P50 auditory-evoked test measured a significant effect on sensory gating, and a Repeatable Battery for Assessment of Neuropsychological Status test measured a significant effect on neurocognition. The subjects did not report any symptoms or side effects, however the leukocyte count of one subject decreased from slightly above normal on the placebo, to slightly below normal when administered the higher dose of DXMBA. After receiving no exposure to the drug, the subject's leukocyte count returned to normal 2 days later.
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 land-grant research university in Gainesville, Florida. It is a senior member of the State University System of Florida, traces its origins to 1853, and has operated continuously on its ...
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.
References
{{Nicotinic acetylcholine receptor modulators
Antipsychotics
3-Pyridyl compounds
Nicotinic agonists
Stimulants
Phenol ethers
Tetrahydropyridines