Physiological signature of a novel potentiator of AMPA receptor signalling.

Autor: Szulc BR; Department of Pharmacology, School of Pharmacy, University College London, London, UK., Hilton ST; Department of Pharmacology, School of Pharmacy, University College London, London, UK. Electronic address: s.hilton@ucl.ac.uk., Ruiz AJ; Department of Pharmacology, School of Pharmacy, University College London, London, UK. Electronic address: a.ruiz@ucl.ac.uk.
Jazyk: angličtina
Zdroj: Molecular and cellular neurosciences [Mol Cell Neurosci] 2018 Oct; Vol. 92, pp. 82-92. Date of Electronic Publication: 2018 Jul 22.
DOI: 10.1016/j.mcn.2018.07.003
Abstrakt: We have synthesized a novel small molecule based on the pyrrolidinone-containing core structure of clausenamide, which is a candidate anti-dementia drug. The synthetic route yielded multi-gram quantities of an isomeric racemate mixture in a short number of steps. When tested in hippocampal slices from young adult rats the compound enhanced AMPA receptor-mediated signalling at mossy fibre synapses, and potentiated inward currents evoked by local application of l-glutamate onto CA3 pyramidal neurons. It facilitated the induction of mossy fibre LTP, but the magnitude of potentiation was smaller than that observed in untreated slices. The racemic mixture was separated and it was shown that only the (-) enantiomer was active. Toxicity analysis indicated that cell lines tolerated the compound at concentrations well above those enhancing synaptic transmission. Our results unveil a small molecule whose physiological signature resembles that of a potent nootropic drug.
(Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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