Optical Control of GABAA Receptors with a Fulgimide-Based Potentiator
- PMID: 32307732
- PMCID: PMC7589408
- DOI: 10.1002/chem.202000710
Optical Control of GABAA Receptors with a Fulgimide-Based Potentiator
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.
© 2020 The Authors. Published by Wiley-VCH GmbH.
Conflict of interest statement
The authors declare no conflict of interest.
Figures
Similar articles
-
GABA-induced uncoupling of GABA/benzodiazepine site interactions is associated with increased phosphorylation of the GABAA receptor.J Neurosci Res. 2014 Aug;92(8):1054-61. doi: 10.1002/jnr.23387. Epub 2014 Apr 10. J Neurosci Res. 2014. PMID: 24723313
-
GABA-induced uncoupling of GABA/benzodiazepine site interactions is mediated by increased GABAA receptor internalization and associated with a change in subunit composition.Neuroscience. 2014 Jan 17;257:119-29. doi: 10.1016/j.neuroscience.2013.10.077. Epub 2013 Nov 9. Neuroscience. 2014. PMID: 24215979
-
The GABAA-BZR complex as target for the development of anxiolytic drugs.Curr Top Med Chem. 2012;12(4):254-69. doi: 10.2174/1568026799078787. Curr Top Med Chem. 2012. PMID: 22204488 Review.
-
Benzodiazepine-insensitive mice generated by targeted disruption of the gamma 2 subunit gene of gamma-aminobutyric acid type A receptors.Proc Natl Acad Sci U S A. 1995 Aug 15;92(17):7749-53. doi: 10.1073/pnas.92.17.7749. Proc Natl Acad Sci U S A. 1995. PMID: 7644489 Free PMC article.
-
[GABA(A) benzodiazepine receptors and epilepsy].Wien Klin Wochenschr. 1990 Mar 30;102(7):197-201. Wien Klin Wochenschr. 1990. PMID: 2160756 Review. German.
Cited by
-
Photopharmacology of Ion Channels through the Light of the Computational Microscope.Int J Mol Sci. 2021 Nov 8;22(21):12072. doi: 10.3390/ijms222112072. Int J Mol Sci. 2021. PMID: 34769504 Free PMC article. Review.
-
Molecular photoswitches in aqueous environments.Chem Soc Rev. 2021 Nov 15;50(22):12377-12449. doi: 10.1039/d0cs00547a. Chem Soc Rev. 2021. PMID: 34590636 Free PMC article. Review.
References
-
- Wietek J., Wiegert J. S., Adeishvili N., Schneider-Warme F., Watanabe H., Tsunoda S., Vogt A., Elstner M., Oertner T., Hegemann P., Science 2014, 344, 409–412. - PubMed