α5IA (LS-193,268) is a nootropic drug invented in 2004 by a team working for Merck, Sharp and Dohme, which acts as a subtype-selective inverse agonist at the benzodiazepine binding site on the GABAA receptor. It binds to α1, α2, α3 and α5 -containing subtypes, with functional selectivity for α5-containing subtypes.[1][2]
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| Other names | LS-193,268 |
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| Elimination half-life | 2-2.5h |
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| Formula | C17H14N8O2 |
| Molar mass | 362.353 g·mol−1 |
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Clinical research
editAdministration of α5IA following alcohol consumption was found to reverse memory impairments induced by alcohol.[3]
In vitro electrophysiology
editRecordings of local field potentials indicate that oral administration of α5IA increases the amplitude of sharp wave ripples which are implicated in memory function in adult wild type rats. The increase in ripple amplitude is not seen in adult male TgF344-AD rats which express human β-amyloid precursor protein (with the Swedish mutation) and human presenilin-1 (with a Δ exon 9 mutation).[4]
See also
editReferences
edit- ^ Sternfeld F, Carling RW, Jelley RA, Ladduwahetty T, Merchant KJ, Moore KW, et al. (April 2004). "Selective, orally active gamma-aminobutyric acidA alpha5 receptor inverse agonists as cognition enhancers". Journal of Medicinal Chemistry. 47 (9): 2176–9. doi:10.1021/jm031076j. PMID 15084116.
- ^ Street LJ, Sternfeld F, Jelley RA, Reeve AJ, Carling RW, Moore KW, et al. (July 2004). "Synthesis and biological evaluation of 3-heterocyclyl-7,8,9,10-tetrahydro-(7,10-ethano)-1,2,4-triazolo[3,4-a]phthalazines and analogues as subtype-selective inverse agonists for the GABA(A)alpha5 benzodiazepine binding site". Journal of Medicinal Chemistry. 47 (14): 3642–57. doi:10.1021/jm0407613. PMID 15214791.
- ^ Atack JR (2008). "GABA(A) receptor subtype-selective efficacy: TPA023, an alpha2/alpha3 selective non-sedating anxiolytic and alpha5IA, an alpha5 selective cognition enhancer". CNS Neuroscience & Therapeutics. 14 (1): 25–35. doi:10.1111/j.1527-3458.2007.00034.x. ISSN 1755-5930. PMC 6494020. PMID 18482097.
- ^ Ratner MH, Downing SS, Guo O, Odamah KE, Stewart TM, Kumaresan V, et al. (September 2021). "Prodromal dysfunction of α5GABA-A receptor modulated hippocampal ripples occurs prior to neurodegeneration in the TgF344-AD rat model of Alzheimer's disease". Heliyon. 7 (9): e07895. doi:10.1016/j.heliyon.2021.e07895. PMC 8449175. PMID 34568591.