Ro4938581

Ro4938581 is a nootropic drug invented in 2009 by a team working for Hoffmann-La Roche, which acts as a subtype-selective inverse agonist at the α5 subtype of the benzodiazepine binding site on the GABAA receptor. It has good selectivity for the α5 subtype and did not produce convulsant or anxiogenic effects in animal studies, making it a promising potential nootropic.[1][2][3] Ro4938581 and a related derivative basmisanil (RG-1662, RO5186582) have subsequently been investigated for the alleviation of cognitive dysfunction in Down syndrome.[4][5]

Ro4938581
Identifiers
IUPAC name
  • 3-Bromo-10-(difluoromethyl)-9H-benzo[f]imidazo[1,5-a][1,2,4]triazolo[1,5-d][1,4]diazepine
CAS Number
PubChem CID
IUPHAR/BPS
ChemSpider
UNII
ChEMBL
Chemical and physical data
FormulaC13H8BrF2N5
Molar mass352.143 g·mol−1
3D model (JSmol)
SMILES
  • FC(F)C(N=C1)=C(N1C2=C3C=C(Br)C=C2)CN4C3=NC=N4
InChI
  • InChI=1S/C13H8BrF2N5/c14-7-1-2-9-8(3-7)13-17-5-19-21(13)4-10-11(12(15)16)18-6-20(9)10/h1-3,5-6,12H,4H2
  • Key:AFJRYPJIKHMNGL-UHFFFAOYSA-N

See also

References
  1. Ballard TM, Knoflach F, Prinssen E, Borroni E, Vivian JA, Basile J, et al. (January 2009). "RO4938581, a novel cognitive enhancer acting at GABAA alpha5 subunit-containing receptors". Psychopharmacology. 202 (1–3): 207–23. doi:10.1007/s00213-008-1357-7. PMID 18936916. S2CID 22011375.
  2. Knust H, Achermann G, Ballard T, Buettelmann B, Gasser R, Fischer H, et al. (October 2009). "The discovery and unique pharmacological profile of RO4938581 and RO4882224 as potent and selective GABAA alpha5 inverse agonists for the treatment of cognitive dysfunction". Bioorganic & Medicinal Chemistry Letters. 19 (20): 5940–4. doi:10.1016/j.bmcl.2009.08.053. PMID 19762240.
  3. Redrobe JP, Elster L, Frederiksen K, Bundgaard C, de Jong IE, Smith GP, et al. (June 2012). "Negative modulation of GABAA α5 receptors by RO4938581 attenuates discrete sub-chronic and early postnatal phencyclidine (PCP)-induced cognitive deficits in rats". Psychopharmacology. 221 (3): 451–68. doi:10.1007/s00213-011-2593-9. PMID 22124672. S2CID 2550795.
  4. Martínez-Cué C, Martínez P, Rueda N, Vidal R, García S, Vidal V, et al. (February 2013). "Reducing GABAA α5 receptor-mediated inhibition rescues functional and neuromorphological deficits in a mouse model of down syndrome". The Journal of Neuroscience. 33 (9): 3953–66. doi:10.1523/JNEUROSCI.1203-12.2013. PMC 6619314. PMID 23447605.
  5. Breindl A (2019). "Inhibiting Inhibition to Treat Down Syndrome Symptoms". BioWorld.


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