Overview
- Suzuki, G. et al. (2007) J. Pharmacol. Exp. Ther. 321, 1144.
Alomone Labs FTIDC inhibits mGluR1-mediated Ca2+ mobilization in U2OS cells.Dose response of normalized inhibition of human mGluR1 receptors mediated, L-Glutamate evoked Ca2+ mobilization by FTIDC (#F-190). IC50 was determined at 1.45 nM. hmGluR1-expressing cells were loaded with calcium-sensitive dye, incubated with a range of concentrations of FTIDC, and stimulated by 15 µM L-Glutamate (EC80). Changes in intracellular Ca2+ following stimulation were detected as changes in maximum relative fluorescence (RLU) using FLIPRTETRA™.
FTIDC is a highly potent and selective allosteric antagonist of mGluR1 receptors and shows very weak potency against human and rat mGluR5 receptors. The inhibition of FTIDC for mGluR1 receptors is shown to be in noncompetitive manner and displays IC50 values of 5.8 and 3.1 nM for human and mouse mGluR1 expressed in CHO cells respectively1.
Studies using chimeric and mutant mGluR1 show that transmembrane (TM) domains 4 to 7, play an important role in the antagonistic properties of FTIDC. The compound has oral activity on recombinant human, mouse, and rat mGluR1 without species differences in its antagonistic activity. The compound is considered to be a valuable tool for elucidating the functions of mGluR1 in rodents and in humans1,2.
Metabotropic glutamate receptors (mGluRs) are G-protein coupled receptors (GPCR) and play an important role in synaptic plasticity and other neuro-physiological and pathological processes including a major role in central sensitization and neuropathic pain. Type 1 mGluRs are mainly found in somatodendritic domains and postsynaptically regulate neuronal excitability and synaptic transmission through several intracellular second messenger systems2,3.
