Overview
- Mabire, D. et al. (2005) J. Med. Chem. 48, 2134.
- Lavreysen, H. et al. (2003) Mol. Pharmacol. 63, 1082.
- Van Wagenen, B.C. et al. (2000) Abstr. Soc. Neurosci. Presentation No. 618, 3.
Alomone Labs NPS 2390 inhibits mGluR1-mediated Ca2+ mobilization in U2OS cells.Dose response of normalized inhibition of human mGluR1 mediated, L-Glutamate evoked Ca2+ mobilization by NPS 2390 (#N-340). IC50 was determined at 56.7 nM. hmGluR1-expressing cells were loaded with calcium-sensitive dye, incubated with a range of concentrations of NPS 2390, 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™.
NPS 2390, a quinoxaline derivative, is a synthetic, potent, selective and non-competitive antagonist of group I metabotropic glutamate receptors comprising mGluR1 and mGluR5 receptors with IC50 values of 5.2 and 8.2 nM respectively7. The compound shows very low affinity towards other mGluR receptors.
Several studies suggest that NPS 2390 acts on a site that is different from the glutamate binding pocket. It is likely that the compound acts at the transmembrane segment VII region of the receptors1-3.
Metabotropic glutamate receptors (mGluRs) are G protein coupled receptors (GPCR) that 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 systems4,5. The mGlu1 receptors play an important role in motor learning and motor coordination whereas mGlu5 receptors contribute to induction of long-term potentiation and associative learning6.
