Stereospecific Inhibition of Ethanol Potentiation on Glycine Receptor by M554 Stereoisomers

Pilar A. Vásquez, Loreto San Martín, Yenifer Argel, Camila Riquelme, Josefa Torres, Felipe Vidal, Francisca Cayuman, Patricio Castro, Jorge Fuentealba, Gustavo Moraga-Cid, Gonzalo Yevenes, Chunyang Jin, Verónica A. Jiménez, Leonardo Guzmán

Research output: Contribution to journalArticlepeer-review


Blocking the interaction between the Gβγprotein and the glycine receptor (GlyR) has emerged as a promising pharmacological strategy to treat acute alcohol intoxication by inhibiting ethanol potentiation on GlyR. M554 is a recently discovered small molecule capable of binding to Gβγwith potent in vitro and in vivo inhibitory activity. This compound has been tested as a mixture of diastereomers, and no information is available concerning the stereospecific activity of each species, which is critical to pursue efforts on lead optimization and drug development. In this work, we explored the differential activity of four M554 stereoisomers by in silico molecular dynamics simulations and electrophysiological experiments. Our results revealed that the (R,R)-M554 stereoisomer is a promising lead compound that inhibits ethanol potentiation of GlyR.

Original languageEnglish
JournalJournal of Chemical Information and Modeling
Publication statusAccepted/In press - 2020

ASJC Scopus subject areas

  • General Chemistry
  • General Chemical Engineering
  • Computer Science Applications
  • Library and Information Sciences

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