Ro4938581

Ro4938581
Systematic (IUPAC) name
3-bromo-10-(difluoromethyl)-9H-benzo[f]imidazo[1,5-a][1,2,4]triazolo[1,5-d][1,4]diazepine
Clinical data
Identifiers
 Yes
PubChem CID 11624499
Chemical data
Formula C13H8BrF2N5
352.14 g/mol

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 RG-1662 have subsequently been investigated for the alleviation of cognitive dysfunction in Down's syndrome.[4][5]

See also

References

  1. ↑ Ballard, T. M.; Knoflach, F. D. R.; Prinssen, E.; Borroni, E.; Vivian, J. A.; Basile, J.; Gasser, R.; Moreau, J. L.; Wettstein, J. G.; Buettelmann, B.; Knust, H.; Thomas, A. W.; Trube, G.; Hernandez, M. C. (2008). "RO4938581, a novel cognitive enhancer acting at GABAA α5 subunit-containing receptors". Psychopharmacology 202 (1–3): 207–223. doi:10.1007/s00213-008-1357-7. PMID 18936916.
  2. ↑ Knust, H.; Achermann, G.; Ballard, T.; Buettelmann, B.; Gasser, R.; Fischer, H.; Hernandez, M. C.; Knoflach, F. D. R.; Koblet, A.; Stadler, H.; Thomas, A. W.; Trube, G.; Waldmeier, P. (2009). "The discovery and unique pharmacological profile of RO4938581 and RO4882224 as potent and selective GABAA α5 inverse agonists for the treatment of cognitive dysfunction". Bioorganic & Medicinal Chemistry Letters 19 (20): 5940–5944. doi:10.1016/j.bmcl.2009.08.053. PMID 19762240.
  3. ↑ Redrobe, J. P.; Elster, L.; Frederiksen, K.; Bundgaard, C.; De Jong, I. E. M.; Smith, G. P.; Bruun, A. T.; Larsen, P. H.; Didriksen, M. (2011). "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): 451–468. doi:10.1007/s00213-011-2593-9. PMID 22124672.
  4. ↑ Martinez-Cue, C.; Martínez, P.; Rueda, N.; Vidal, R.; García, S.; Vidal, V.; Corrales, A.; Montero, J. A.; Pazos, A.; Flórez, J.; Gasser, R.; Thomas, A. W.; Honer, M.; Knoflach, F.; Trejo, J. L.; Wettstein, J. G.; Hernández, M. -C. (2013). "Reducing GABAA  5 Receptor-Mediated Inhibition Rescues Functional and Neuromorphological Deficits in a Mouse Model of Down Syndrome". Journal of Neuroscience 33 (9): 3953–3966. doi:10.1523/JNEUROSCI.1203-12.2013. PMID 23447605.
  5. ↑ Inhibiting Inhibition to Treat Down Syndrome Symptoms