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Rescue of deficient amygdala tonic γ-aminobutyric acidergic currents in the Fmr-/y mouse model of fragile X syndrome by a novel γ-aminobutyric acid type A receptor-positive allosteric modulator. Martinez Botella G, Salituro FG, Harrison BL, et al. A series of heterocyclic bioisosteres were synthesized to specifically overcome short half-lives in vivo.The oxadiazole MP-III-080 (34) and oxazole KRM-II-81 (36) underwent pharmacokinetic studies and were both found to exist in plasma and brain samples in high levels.A series of ligands based off HZ-166 (3) were synthesized.
In addition, work on analogs of 52 produced MP-III-004 (63), an α5 subtype selective ligand with reduced efficacy at the α1, α2 and α3 subtypes as compared to 52, as well as the very potent α5 positive allosteric modulator MP-III-022 (65).Martinez Botella G, Salituro FG, Harrison BL, et al. The synthetic neuroactive steroid SGE-516 reduces status epilepticus and neuronal cell death in a rat model of soman intoxication. Progress report on new antiepileptic drugs: A summary of the Twelfth Eilat Conference (EILAT XII). EEG-β/γ spectral power elevation in rat: a translatable biomarker elicited by GABA(Aα2/3)-positive allosteric modulators at nonsedating anxiolytic doses.
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