MPEP

MPEP is a selective antagonist for the metabotropic glutamate receptor subtype 5 (mGluR5) with IC50 of 36 nM. MPEP is a significantly more potent antagonist derived by structural derivatization around SIB-1757 and SIB-1893. MPEP has no agonist or antagonist activities at the human mGlu1b receptor expressed in CHO-K1 cells at concentrations up to 30 μM. When tested at group II and III receptors, MPEP does not show agonist or antagonist activity at 100 μM on human mGlu2, -3, -4a, -7b, and -8a receptors nor at 10 μM on the human mGlu6 receptor. MPEP has no significant effect at 100 μM on human NMDA (NMDA1A/2A), rat AMPA (Glu3-(flop)) and human kainate (Glu6-(IYQ)) receptor subtypes nor at 10 μM on the human NMDA1A/2B receptor. In rat neonatal brain slices, MPEP inhibits DHPG-stimulated PI hydrolysis with a potency and selectivity similar to that observed on human mGlu receptors. MPEP is centrally active following peripheral application and selectively inhibits group I agonist effects in the rat hippocampal CA1 area in vivo. MPEP produces anxiolytic-like effects in several tests such as the Vogel test in rats, the elevated plus-maze test in rats as well as the four-plate test in mice. MPEP also exerts antidepressant-like effects in the tail suspension test in mice. MPEP does not induce sedation nor disturb motor coordination in animals. [2] MPEP also acts as a positive allosteric modulator for the human metabotropic glutamate receptor 4 (hmGluR4). Blocking of mGluR5 with MPEP is able to rescue two major Fragile X Syndrome mouse model phenotypes. ?