Controlling Ca2+ Permeable α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid (AMPA) Receptors with Photochromic Ion Channel Blockers

Niels G Nørager; Mette H Poulsen; Kristian Strømgaard

doi:10.1021/acs.jmedchem.8b00756

Controlling Ca²⁺ Permeable α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid (AMPA) Receptors with Photochromic Ion Channel Blockers

J Med Chem. 2018 Sep 13;61(17):8048-8053. doi: 10.1021/acs.jmedchem.8b00756. Epub 2018 Aug 31.

Authors

Niels G Nørager¹, Mette H Poulsen¹, Kristian Strømgaard¹

Affiliation

¹ Department of Drug Design and Pharmacology , University of Copenhagen , Universitetsparken 2 , DK-2100 Copenhagen , Denmark.

PMID: 30125106
DOI: 10.1021/acs.jmedchem.8b00756

Abstract

Ionotropic glutamate receptors (iGluRs) play a critical role in normal brain function and neurodegenerative diseases. Development of light-dependent compounds would enable studies of iGluRs within intact mammalian neural tissue, as light is noninvasive and can be applied with high spatiotemporal precision. Here we develop a potent photochromic antagonist that selectively targets the Ca²⁺ permeable AMPA-type of iGuRs, thus providing an important tool to study the contribution of AMPA-type iGluRs on neuronal activity.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Azo Compounds / chemistry
Azo Compounds / pharmacology*
Calcium / metabolism*
Cells, Cultured
Female
Light
Models, Molecular
Molecular Structure
Neurotransmitter Agents / chemistry
Neurotransmitter Agents / pharmacology*
Oocytes / cytology
Oocytes / drug effects
Oocytes / metabolism*
Polyamines / chemistry
Rats
Receptors, AMPA / antagonists & inhibitors*
Structure-Activity Relationship
Xenopus laevis

Substances

Azo Compounds
Neurotransmitter Agents
Polyamines
Receptors, AMPA
azobenzene
Calcium
glutamate receptor ionotropic, AMPA 1