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GTS-21

Chemical compound

Summary

Chemical compound

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. Despite study of the molecule since 1990s, as of 2025 it has not been shown to be effective in clinical trials.

GTS-21 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. Activation of the α7 nAChR has been shown to have neuroprotective effects which has made GTS-21 a focus of research in the treatment of neurological diseases.

The laboratory name GTS-21 means that it was the 21st chemical compound created by Gainesville (University of Florida in Gainesville) and Tokushima (Taiho Pharmaceutical) Scientists while DMXBA stands for 3-2,4-dimethoxybenzylidene anabaseine.

Research and clinical trial history

In early research in the 1990s, GTS-21 and its active metabolites were shown to improve cognition in healthy adult men (nootropic effect) as well as neuroprotective effects in animal models and neuronal cell cultures. The results of early studies led to GTS-21 being investigated for the treatment of Alzheimer's disease, nicotine dependence, and for schizophrenia.

Despite promising early research, clinical trials using GTS-21 have failed to show clinically significant efficacy and, as of 2025, no trial has proceeded beyond phase 2. Trials have using DMXBA to treat schizophrenia were completed in the 2000s but these trials were discontinued during phase II. More recent trials focusing on other neurological diseases including Alzheimer's, autism, ADHD, and nicotine use have also been discontinued or withdrawn.

References

References

  1. (1997). "Functional characterization of the novel neuronal nicotinic acetylcholine receptor ligand GTS-21 in vitro and in vivo". Pharmacology, Biochemistry, and Behavior.
  2. (September 1997). "3-[2,4-Dimethoxybenzylidene]anabaseine (DMXB) selectively activates rat alpha7 receptors and improves memory-related behaviors in a mecamylamine-sensitive manner". Brain Research.
  3. (September 1987). "[Thirteen-year-old girl presenting chorea after treatment of hyperthyroidism]". No to Hattatsu = Brain and Development.
  4. (December 1998). "Analysis of 3-(4-hydroxy, 2-Methoxybenzylidene)anabaseine selectivity and activity at human and rat alpha-7 nicotinic receptors". The Journal of Pharmacology and Experimental Therapeutics.
  5. (March 2003). "Safety, pharmacokinetics, and effects on cognitive function of multiple doses of GTS-21 in healthy, male volunteers". Neuropsychopharmacology.
  6. (March 1998). "Neuroprotective effects of 2,4-dimethoxybenzylidene anabaseine (DMXB) and tetrahydroaminoacridine (THA) in neocortices of nucleus basalis lesioned rats". Brain Research.
  7. (January 1998). "Nicotinic alpha 7 receptors protect against glutamate neurotoxicity and neuronal ischemic damage". Brain Research.
  8. (May 2002). "Alpha7 nicotinic receptor activation inhibits ethanol-induced mitochondrial dysfunction, cytochrome c release and neurotoxicity in primary rat hippocampal neuronal cultures". Journal of Neurochemistry.
  9. (July 1999). "Metabolism and disposition of GTS-21, a novel drug for Alzheimer's disease". Xenobiotica; the Fate of Foreign Compounds in Biological Systems.
  10. (August 2000). "The brain alpha7 nicotinic receptor may be an important therapeutic target for the treatment of Alzheimer's disease: studies with DMXBA (GTS-21)". Behavioural Brain Research.
  11. (May 2004). "Advances in pharmacotherapy for tobacco dependence". Expert Opinion on Emerging Drugs.
  12. (June 2004). "Alpha-7 nicotinic receptor agonists: potential new candidates for the treatment of schizophrenia". Psychopharmacology.
  13. (October 2007). "Treating schizophrenia symptoms with an alpha7 nicotinic agonist, from mice to men". Biochemical Pharmacology.
  14. (August 2008). "Initial phase 2 trial of a nicotinic agonist in schizophrenia". The American Journal of Psychiatry.
  15. {{ClinicalTrialsGov. NCT00100165. Phase 2 Trial of the Nicotinic Agonist 3-(2,4 Dimethoxybenzylidene Anabaseine) in Schizophrenia
  16. {{ClinicalTrialsGov. NCT00414622. GTS21-201 for Alzheimer Disease:GTS-21 Administered Daily for 28 Days to Participants With Probable Alzheimer's Disease
  17. {{ClinicalTrialsGov. NCT01400477. Nicotinic Receptors and Schizophrenia
  18. {{ClinicalTrialsGov. NCT02111551. Phase I Nicotinic Agonist Treatment Trial for Autism
  19. {{ClinicalTrialsGov. NCT00419445. Safety and Efficacy of GTS21 in Adults With Attention-deficit Hyperactivity Disorder
  20. {{ClinicalTrialsGov. NCT02432066. Effects of GTS-21 on Smoking Behavior and Neurocognitive Functions
Wikipedia Source

This article was imported from Wikipedia and is available under the Creative Commons Attribution-ShareAlike 4.0 License. Content has been adapted to SurfDoc format. Original contributors can be found on the article history page.

antipsychotics 3-pyridyl-compounds nicotinic-agonists stimulants phenol-ethers tetrahydropyridines
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