Description
Metabotropic glutamate receptors (mGluRs), mediate excitatory synaptic transmission in the central nervous system. Potent and selective antagonists of the type I mGluRs (mGluR1 and mGluR5) are of interest as novel therapeutics for the treatment of various CNS disorders, such as pain, epilepsy, and stroke. NPS 2390 is a first generation quinoxaline derivative that acts as a noncompetitive antagonist of mGluR1 and mGluR5 with IC
50 values equal to 5.2 and 82 nM, respectively). At concentrations up to 30 μM, NPS 2390 does not affect mGluR2 or mGluR8 or a standard collection of 37 additional receptors, ion channels, and enzymes. At a dose of 10 mg/kg, NPS 2390 displaced the specifically bound mGlu1R-
selective antagonist, [
3H]R214127, in rat cerebellum.
Uses
NPS 2390 is an inhibitor of CaSR (Calcium-sensing recpetor). NPS 2390 up-regulated anti-apoptotic protein Bcl-2 expression and down-regulated pro-apoptotic protein Bax.
Uses
Metabotropic glutamate receptors (mGluRs), mediate excitatory synaptic transmission in the central nervous system. Potent and selective antagonists of the type I mGluRs (mGluR1 and mGluR5) are of interest as novel therapeutics for the treatment of various CNS disorders, such as pain, epilepsy, and stroke. NPS 2390 is a first generation quinoxaline derivative that acts as a noncompetitive antagonist of mGluR1 and mGluR5 with IC50 values equal to 5.2 and 82 nM, respectively). At concentrations up to 30 μM, NPS 2390 does not affect mGluR2 or mGluR8 or a standard collection of 37 additional receptors, ion channels, and enzymes. At a dose of 10 mg/kg, NPS 2390 displaced the specifically bound mGlu1R-selective antagonist, [3H]R214127, in rat cerebellum.
References
[1] FRANCESCO FERRAGUTI F N Luca Crepaldi. Metabotropic glutamate 1 receptor: current concepts and perspectives.[J]. Pharmacological Reviews, 2008, 60 4: 536-581. DOI:
10.1124/pr.108.000166[2] DOMINIQUE MABIRE. Synthesis, StructureActivity Relationship, and Receptor Pharmacology of a New Series of Quinoline Derivatives Acting as Selective, Noncompetitive mGlu1 Antagonists[J]. Journal of Medicinal Chemistry, 2005, 48 6: 2134-2153. DOI:
10.1021/jm049499o[3] De Souza, F.I., Zumiotti, A.V., and Da Silva, C.F. Neuregulins 1-α and 1-β on the regeneration the peripheral nerves[J]. Acta Ortop Bras.
[4] HILDE LAVREYSEN. [3H]R214127: a novel high-affinity radioligand for the mGlu1 receptor reveals a common binding site shared by multiple allosteric antagonists.[J]. Molecular Pharmacology, 2003, 63 5: 1082-1093. DOI:
10.1124/mol.63.5.1082
