ORG-26576

ORG-26576 is an ampakine originally developed by Cortex Pharmaceuticals and then licensed to Organon International for development. In animal studies it has been shown to effectively potentiate AMPA receptor function, leading to increased BDNF release and enhanced neuronal differentiation and survival, as well as producing nootropic effects in standardised assays.[1][2][3][4][5][6] Development as an antidepressant has been halted due to a failed Phase II trial for major depressive disorder.[7]

ORG-26576
Identifiers
  • (7S)-9-oxa-3,11-diazatricyclo[8.4.0.03,7]tetradeca-1(10),11,13-trien-2-one
CAS Number
PubChem CID
ChemSpider
UNII
Chemical and physical data
FormulaC11H12N2O2
Molar mass204.229 g·mol−1
3D model (JSmol)
  • C1C[C@H]2COC3=C(C=CC=N3)C(=O)N2C1
  • InChI=1S/C11H12N2O2/c14-11-9-4-1-5-12-10(9)15-7-8-3-2-6-13(8)11/h1,4-5,8H,2-3,6-7H2/t8-/m0/s1
  • Key:FIKUEZUFASUKAH-QMMMGPOBSA-N

See also

References
  1. Jordan GR, McCulloch J, Shahid M, Hill DR, Henry B, Horsburgh K (August 2005). "Regionally selective and dose-dependent effects of the ampakines Org 26576 and Org 24448 on local cerebral glucose utilisation in the mouse as assessed by 14C-2-deoxyglucose autoradiography". Neuropharmacology. 49 (2): 254–64. doi:10.1016/j.neuropharm.2005.03.011. PMID 15993447. S2CID 24805124.
  2. Su XW, Li XY, Banasr M, Koo JW, Shahid M, Henry B, Duman RS (October 2009). "Chronic treatment with AMPA receptor potentiator Org 26576 increases neuronal cell proliferation and survival in adult rodent hippocampus". Psychopharmacology. 206 (2): 215–22. doi:10.1007/s00213-009-1598-0. PMID 19603152. S2CID 19408716.
  3. Hamlyn E, Brand L, Shahid M, Harvey BH (October 2009). "The ampakine, Org 26576, bolsters early spatial reference learning and retrieval in the Morris water maze: a subchronic, dose-ranging study in rats". Behavioural Pharmacology. 20 (7): 662–7. doi:10.1097/FBP.0b013e328331ba1b. PMID 19741506. S2CID 27814943.
  4. Bursi R, Erdemli G, Campbell R, Hutmacher MM, Kerbusch T, Spanswick D, et al. (December 2011). "Translational PK-PD modelling of molecular target modulation for the AMPA receptor positive allosteric modulator Org 26576". Psychopharmacology. 218 (4): 713–24. doi:10.1007/s00213-011-2365-6. PMID 21647578. S2CID 20634325.
  5. Jardemark K, Marcus MM, Malmerfelt A, Shahid M, Svensson TH (May 2012). "Differential effects of AMPA receptor potentiators and glycine reuptake inhibitors on antipsychotic efficacy and prefrontal glutamatergic transmission". Psychopharmacology. 221 (1): 115–31. doi:10.1007/s00213-011-2554-3. PMID 22068461. S2CID 253749292.
  6. Fumagalli F, Calabrese F, Luoni A, Shahid M, Racagni G, Riva MA (February 2012). "The AMPA receptor potentiator Org 26576 modulates stress-induced transcription of BDNF isoforms in rat hippocampus". Pharmacological Research. 65 (2): 176–81. doi:10.1016/j.phrs.2011.10.004. PMID 22079295.
  7. Machado-Vieira R, Henter ID, Zarate CA (May 2017). "New targets for rapid antidepressant action". Progress in Neurobiology. 152: 21–37. doi:10.1016/j.pneurobio.2015.12.001. PMC 4919246. PMID 26724279.


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