α₅IA (LS-193,268) is a

nootropic Nootropics ( or ) (colloquially brain supplements, smart drugs, cognitive enhancers, memory enhancers, or brain boosters) are chemical substances which purportedly improve cognitive functions, such as attention, memory, wakefulness, and self ...

drug invented in 2004 by a team working for Merck, Sharp and Dohme, which acts as a subtype-selective

inverse agonist In pharmacology, an inverse agonist is a drug that binds to the same receptor as an agonist but induces a pharmacological response opposite to that of the agonist. A neutral antagonist has no activity in the absence of an agonist or inverse agon ...

at the

benzodiazepine Benzodiazepines (BZD, BDZ, BZs), colloquially known as "benzos", are a class of central nervous system (CNS) depressant, depressant drugs whose core chemical structure is the fusion of a benzene ring and a diazepine ring. They are prescribed t ...

binding site on the GABA_A

receptor Receptor may refer to: * Sensory receptor, in physiology, any neurite structure that, on receiving environmental stimuli, produces an informative nerve impulse *Receptor (biochemistry), in biochemistry, a protein molecule that receives and respond ...

. It binds to α₁, α₂, α₃ and α₅ -containing subtypes, with functional selectivity for α₅-containing subtypes.

Clinical research

Administration of α₅IA following alcohol consumption was found to reverse memory impairments induced by alcohol.

''In vitro'' electrophysiology

Recordings of

local field potentials Local field potentials (LFP) are transient electrical signals generated in nerves and other tissues by the summed and synchronous electrical activity of the individual cells (e.g. neurons) in that tissue. LFP are "extracellular" signals, meaning t ...

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).

References

{{DEFAULTSORT:A5ia GABAA receptor negative allosteric modulators Isoxazoles Aromatic ethers Phthalazines Triazoles

Clinical research

''In vitro'' electrophysiology

See also

References