RPR104632 is a specific antagonist of NMDA receptor, with potent neuroprotective properties.
RPR104632 antagonizes the binding of [3H]5,7-dichlorokynurenic acid to the rat cerebral cortex, with a Ki of 4.9 nM. RPR104632 inhibits [3H]N-[1-(2-thienyl)cyclohexyl]-3,4-piperidine ([3H]TCP) binding in the presence of N-methyl-D-aspartate (NMDA) (IC50 = 55 nM). RPR104632 inhibits the NMDA-evoked increase in guanosine 3',5'-cyclic monophosphate (cGMP) levels of neonatal rat cerebellar slices (IC50 = 890 nM) in a non-competitive manner and markedly reduces NMDA-induced neurotoxicity in rat hippocampal slices and in cortical primary cell cultures. MK-801 (1 μM) completely protects the CA1 and CA3 pyramidal neurones against NMDA-induced toxicity, but these effects are not blocked by glycine. RPR104632 produces a significant and consistent neuroprotective effect towards all the NMDA-induced toxicity and has no effect when it is added alone at concentrations up to 10 μM. RPR104632 has neuroprotective potencies, with EC50 of 4 μM[1].
[1]. Boireau A, et al. Neuroprotective effects of RPR 104632, a novel antagonist at the glycine site of the NMDA receptor, in vitro. Eur J Pharmacol. 1996 Apr 11;300(3):237-46.