Overview
- Zheng, G.Z. et al. (2005) J. Med. Chem. 48, 7374.
- Zhu, C.Z. et al. (2008) Eur. J. Pharmacol. 580, 314.
Alomone Labs A-794278 inhibits mGluR1-mediated Ca2+ mobilization in U2OS cells.Dose-response of A-794278 (#A-435) normalized inhibition of human mGluR1-mediated, L-glutamate-evoked Ca2+ mobilization. Cells were loaded with calcium-sensitive dye, incubated with a range of A-794278 concentrations, and stimulated with 5 µM L-glutamate (EC80). Changes in intracellular Ca2+ following stimulation were detected as changes in maximum relative fluorescence (RLU) using FLIPRTETRA™. IC50 was determined at 4.16 nM.
A-794278 is a potent, non-competitive antagonist of mGluR1. It is a triazafluorenone derivative that also antagonizes mGluR5 receptors. It demonstrates IC50 values of 4.1 nM and 147 nM for mGluR1 and mGluR5, respectively1. A-794278 binds to a putative allosteric recognition site located within the seven-transmembrane domain of the receptor1,2.
Glutamate is the most abundant excitatory neurotransmitter in the central nervous system. It modulates the activity of many types of synapses by activating in part metabotropic glutamate receptors (mGluRs). mGluRs consist of three groups: I, II, and III with a total of eight subtypes, mGluR1 to mGluR8. mGluR1 plays an important role in the central sensitization of pain and in a variety of functions with potential implications in neurological and psychiatric disorders1,2.
