GTS-21

GTS-21
Clinical data
Synonyms 3-(2,4-dimethoxy-benzylidene)anabaseine
Identifiers
PubChem CID
ChemSpider
UNII
Chemical and physical data
Formula C19H20N2O2
Molar mass 308.374
3D model (JSmol)
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GTS-21 (DMBX-A) is a derivative of the natural product anabaseine that acts as a partial agonist at neural nicotinic acetylcholine receptors. It binds to both the α4β2 and α7 subtypes, but activates only the α7 to any significant extent.[1][2]

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] nicotine dependence,[10] and, most significantly, for schizophrenia.[11][12][13][14][15]

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.[16] DMXB-A – 3-2,4-dimethoxybenzylidene anabaseine.

References

  1. ↑ Briggs CA, Anderson DJ, Brioni JD, Buccafusco JJ, Buckley MJ, Campbell JE, Decker MW, Donnelly-Roberts D, Elliott RL, Gopalakrishnan M, Holladay MW, Hui YH, Jackson WJ, Kim DJ, Marsh KC, O'Neill A, Prendergast MA, Ryther KB, Sullivan JP, Arneric SP. Functional characterization of the novel neuronal nicotinic acetylcholine receptor ligand GTS-21 in vitro and in vivo. Pharmacology Biochemistry and Behavior. 1997 May-Jun;57(1-2):231-41. PMID 9164577
  2. ↑ Meyer EM, Tay ET, Papke RL, Meyers C, Huang GL, de Fiebre CM. 3-[2,4-Dimethoxybenzylidene]anabaseine (DMXB) selectively activates rat alpha7 receptors and improves memory-related behaviors in a mecamylamine-sensitive manner. Brain Research. 1997 Sep 12;768(1-2):49-56. PMID 9369300
  3. ↑ Meyer EM, Kuryatov A, Gerzanich V, Lindstrom J, Papke RL (Dec 1998). "Analysis of 3-(4-hydroxy, 2-Methoxybenzylidene)anabaseine selectivity and activity at human and rat alpha-7 nicotinic receptors". Journal of Pharmacology and Experimental Therapeutics. 287 (3): 918–25. PMID 9864273.
  4. ↑ Kitagawa H, Takenouchi T, Azuma R, Wesnes KA, Kramer WG, Clody DE, Burnett AL (Mar 2003). "Safety, pharmacokinetics, and effects on cognitive function of multiple doses of GTS-21 in healthy, male volunteers". Neuropsychopharmacology. 28 (3): 542–51. doi:10.1038/sj.npp.1300028. PMID 12629535.
  5. ↑ Meyer EM, King MA, Meyers C (Mar 1998). "Neuroprotective effects of 2,4-dimethoxybenzylidene anabaseine (DMXB) and tetrahydroaminoacridine (THA) in neocortices of nucleus basalis lesioned rats". Brain Research. 786 (1–2): 252–4. doi:10.1016/s0006-8993(97)00300-4. PMID 9555043.
  6. ↑ Shimohama S, Greenwald DL, Shafron DH, Akaika A, Maeda T, Kaneko S, Kimura J, Simpkins CE, Day AL, Meyer EM (Jan 1998). "Nicotinic alpha 7 receptors protect against glutamate neurotoxicity and neuronal ischemic damage". Brain Research. 779 (1–2): 359–63. doi:10.1016/s0006-8993(97)00194-7. PMID 9473725.
  7. ↑ Li Y, Meyer EM, Walker DW, Millard WJ, He YJ, King MA (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. 81 (4): 853–8. doi:10.1046/j.1471-4159.2002.00891.x. PMID 12065644.
  8. ↑ de Fiebre NC, de Fiebre CM. Alpha 7 nicotinic acetylcholine receptor-mediated protection against ethanol-induced neurotoxicity. Alcohol. 2003 Nov;31(3):149-53. PMID 14693263
  9. ↑ Kem WR (Aug 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): 169–81. doi:10.1016/s0166-4328(00)00211-4. PMID 10942043.
  10. ↑ 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/eoed.9.1.39.32951. PMID 15155135.
  11. ↑ Simosky JK, Stevens KE, Freedman R (Apr 2002). "Nicotinic agonists and psychosis". Current Drug Targets. CNS and Neurological Disorders. 1 (2): 149–62. doi:10.2174/1568007024606168. PMID 12769624.
  12. ↑ Martin LF, Kem WR, Freedman R (Jun 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. PMID 15205879.
  13. ↑ Olincy A, Harris JG, Johnson LL, Pender V, Kongs S, Allensworth D, Ellis J, Zerbe GO, Leonard S, Stevens KE, Stevens JO, Martin L, Adler LE, Soti F, Kem WR, Freedman R (Jun 2006). "Proof-of-concept trial of an alpha7 nicotinic agonist in schizophrenia". Archives of General Psychiatry. 63 (6): 630–8. doi:10.1001/archpsyc.63.6.630. PMID 16754836.
  14. ↑ Olincy A, Stevens KE (Oct 2007). "Treating schizophrenia symptoms with an alpha7 nicotinic agonist, from mice to men". Biochemical Pharmacology. 74 (8): 1192–201. doi:10.1016/j.bcp.2007.07.015. PMC 2134979. PMID 17714692.
  15. ↑ Freedman R, Olincy A, Buchanan RW, Harris JG, Gold JM, Johnson L, Allensworth D, Guzman-Bonilla A, Clement B, Ball MP, Kutnick J, Pender V, Martin LF, Stevens KE, Wagner BD, Zerbe GO, Soti F, Kem WR (Apr 2008). "Initial Phase 2 Trial of a Nicotinic Agonist in Schizophrenia". American Journal of Psychiatry. 165 (8): 1040–7. doi:10.1176/appi.ajp.2008.07071135. PMC 3746983. PMID 18381905.
  16. ↑ William Kem, Ferenc Soti, Kristin Wildeboer, Susan LeFrancois, Kelly MacDougall, Dong-Qing Wei, Kuo-Chen Chou, Hugo R. Arias (2006). "The Nemertine Toxin Anabaseine and Its Derivative DMXBA (GTS-21): Chemical and Pharmacological Properties". Marine Drugs. 4 (3): 255–273. doi:10.3390/md403255. PMC 3663414.

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