GTS-21 (also known asDMXBA orDMBX-anabaseine) is aninvestigational new drug being studied for the treatment ofneurodegenerative diseases andpsychiatric 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 thenatural productanabaseine that acts as apartial agonist at neuralnicotinic acetylcholine receptors (nAChRs). It binds to both theα4β2 andα7subtypes, but activates only the α7 to any significant extent.[1][2] 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 the21st chemical compound created byGainesville (University of Florida inGainesville) andTokushima (Taiho Pharmaceutical)Scientists[3] while DMXBA stands for 3-2,4-dimethoxybenzylideneanabaseine.
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.[15] More recent trials focusing on other neurological diseases including Alzheimer's, autism, ADHD, and nicotine use have also been discontinued or withdrawn.[16][17][18][19][20]
^Briggs CA, Anderson DJ, Brioni JD, Buccafusco JJ, Buckley MJ, Campbell JE, et al. (1997). "Functional characterization of the novel neuronal nicotinic acetylcholine receptor ligand GTS-21 in vitro and in vivo".Pharmacology, Biochemistry, and Behavior.57 (1–2):231–241.doi:10.1016/S0091-3057(96)00354-1.PMID9164577.S2CID205923953.
^Meyer EM, Tay ET, Papke RL, Meyers C, Huang GL, de Fiebre CM (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.768 (1–2):49–56.doi:10.1016/S0006-8993(97)00536-2.PMID9369300.S2CID13104716.
^Yokoyama T, Ishikawa T, Ban K, Saitoh H (September 1987). "[Thirteen-year-old girl presenting chorea after treatment of hyperthyroidism]".No to Hattatsu = Brain and Development.19 (5):408–414.PMID3663414.
^Meyer EM, Kuryatov A, Gerzanich V, Lindstrom J, Papke RL (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.287 (3):918–925.PMID9864273.
^Meyer EM, King MA, Meyers C (March 1998). "Neuroprotective effects of 2,4-dimethoxybenzylidene anabaseine (DMXB) and tetrahydroaminoacridine (THA) in neocortices of nucleus basalis lesioned rats".Brain Research.786 (1–2):252–254.doi:10.1016/s0006-8993(97)00300-4.PMID9555043.S2CID325503.
^Shimohama S, Greenwald DL, Shafron DH, Akaika A, Maeda T, Kaneko S, et al. (January 1998). "Nicotinic alpha 7 receptors protect against glutamate neurotoxicity and neuronal ischemic damage".Brain Research.779 (1–2):359–363.doi:10.1016/s0006-8993(97)00194-7.PMID9473725.S2CID54342132.
^Azuma R, Komuro M, Korsch BH, Andre JC, Onnagawa O, Black SR, et al. (July 1999). "Metabolism and disposition of GTS-21, a novel drug for Alzheimer's disease".Xenobiotica; the Fate of Foreign Compounds in Biological Systems.29 (7):747–762.doi:10.1080/004982599238362.PMID10456692.
^Kem WR (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.113 (1–2):169–181.doi:10.1016/s0166-4328(00)00211-4.PMID10942043.S2CID39523754.
^Foulds J, Burke M, Steinberg M, Williams JM, Ziedonis DM (May 2004). "Advances in pharmacotherapy for tobacco dependence".Expert Opinion on Emerging Drugs.9 (1):39–53.doi:10.1517/14728214.9.1.39.PMID15155135.S2CID219187104.
^Martin LF, Kem WR, Freedman R (June 2004). "Alpha-7 nicotinic receptor agonists: potential new candidates for the treatment of schizophrenia".Psychopharmacology.174 (1):54–64.doi:10.1007/s00213-003-1750-1.PMID15205879.S2CID21557412.
^Clinical trial numberNCT00100165 for "Phase 2 Trial of the Nicotinic Agonist 3-(2,4 Dimethoxybenzylidene Anabaseine) in Schizophrenia" atClinicalTrials.gov
^Clinical trial numberNCT00414622 for "GTS21-201 for Alzheimer Disease:GTS-21 Administered Daily for 28 Days to Participants With Probable Alzheimer's Disease" atClinicalTrials.gov
