It is systemically active, occupying central mGluR1 receptors in the rat cerebellum and thalamus (ED50 = 40 and 14 µg/kg, respectively) when administered subcutaneously1. JNJ 16259685 inhibits synaptic activation of mGluR1 in Purkinje cells in cerebellar slices with IC50 of 19 nM2.
- Alomone Labs JNJ 16259685 inhibits mGluR1-mediated Ca2+ mobilization in U2OS cells.Dose-response of JNJ 16259685 (#J-110) normalized inhibition of human mGluR1-mediated, L-Glutamate-evoked Ca2+ mobilization.
Cells were loaded with a calcium-sensitive dye, incubated with a range of JNJ 16259685 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™.
JNJ 16259685 is a potent, specific, and non-competitive antagonist of mGluR1 displaying an IC50 of 19 nM1. The compound shows a much lower potency towards mGluR5 receptor1,2.
Glutamate is the most abundant excitatory neurotransmitter in the central nervous system and it modulates 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 various physiological functions including regulating ion channels, synaptic transmission, and synaptic plasticity2.