MPEP GluR 길항제

Inactive against other group I/II/III metabotropic glutamate receptors.

MPEP has no appreciable agonist or antagonist activity at the closely related recombinant human mGlu1b receptor expressed in CHO-K1 cells or a purinoreceptor endogenously expressed in L(tk^-) cells up to concentrations of 100 μM. Furthermore, this compound shows no appreciable agonist or antagonist activity in cAMP accumulation or [³⁵S]-GTPγS binding assays at the recombinant human group II and III metabotropic receptors (human mGlu2, -3, -4a, -6, -7b, -8a) as well as the human NMDA (NMDAR1A/2A, -1A/2B), rat AMPA (GluR3) and human kainate (GluR6) receptor subtypes. In slices of rat neonatal hippocampus, striatum, and cortex but not cerebellum, it inhibits DHPG-stimulated PI hydrolysis with IC50 of 8.0 nM, 20.5 nM, and 17.9 nM, respectively. [1] This chemical positively modulates the hmGluR4 in a recombinant expression system, and the effect is fully dependent on the activation of the orthosteric agonist _L-AP4. [3]

When microiontophoretically applied into the brain of rats, MPEP reduces DHPG-induced excitations but not the excitations induced by AMPA. Following intravenous administration, this compound produces a dose-dependent inhibition of DHPG-induced but not AMPA-induced excitations with a rapid onset of action. Oral administration of this chemical also exhibits excellent anti-hyperalgesic activity in the Complete Freund's Adjuvant and turpentine models of inflammatory pain. [1] It (1-30 mg/kg) induces anxiolytic-like effects in the conflict drinking test and the elevated plus-maze test in rats as well as in the four-plate test in mice. This compound (1-20 mg/kg) shortens the immobility time in a tail suspension test in mice, but it is inactive in the behavioural despair test in rats. It has no effect on locomotor activity or motor coordination. [2] This chemical significantly reduces fmr1 but not wild-type center square entries and duration. In open field tests, it reduces fmr1^tm1Cgr center field behavior to one indistinguishable from wild-type. It produces a significant reduction of total locomotor activity in three of four groups tested, at both 10 mg/kg and 30 mg/kg. [4]