Optical Control of GABAA Receptors with a Fulgimide-Based Potentiator

Chemistry. 2020 Oct 6;26(56):12722-12727. doi: 10.1002/chem.202000710. Epub 2020 Sep 11.

Abstract

Optogenetic and photopharmacological tools to manipulate neuronal inhibition have limited efficacy and reversibility. We report the design, synthesis, and biological evaluation of Fulgazepam, a fulgimide derivative of benzodiazepine that behaves as a pure potentiator of ionotropic γ-aminobutyric acid receptors (GABAA Rs) and displays full and reversible photoswitching in vitro and in vivo. The compound enables high-resolution studies of GABAergic neurotransmission, and phototherapies based on localized, acute, and reversible neuroinhibition.

Keywords: GABAA Receptors; fulgimides; in vivo; photopharmacology.

MeSH terms

  • Benzodiazepines
  • Receptors, GABA-A / metabolism*
  • gamma-Aminobutyric Acid

Substances

  • Receptors, GABA-A
  • Benzodiazepines
  • gamma-Aminobutyric Acid