MDL-29951

Description: MDL-29951 is a potent glycine antagonist of NMDA (N-methyl-D-aspartate) receptor activation with Ki value of 0.14 uM in an in vitro and in vivo 3Hglycine binding assay. MDL 100, 748 and MDL 29, 951 are approximately 2000-fold selective for the glycine binding site relative to the glutamate recognition sites.The MDL29951-activated receptor exhibits other activities associated with GPCR-mediated signaling, including G protein-dependent activation of extracellular signal-regulated kinase 1 and 2 (ERK1/2) and recruitment of beta-arrestin. MDL29951 did not activate any of the known uracil or adenine nucleotide-activated P2Y receptors or cysteinyl leukotriene receptors. Galphai- and Galphaq-dependent signaling responses also were observed in primary rat oligodendrocytes in the presence of MDL29951. Moreover, MDL29951 diminished myelination in primary oligodendrocytes isolated from heterozygous mice but had no effect on myelination in oligodendrocytes from GPR17 knockout mice. Effects of a small-molecule GPR17 agonist observed during oligodendrocyte differentiation support the idea that development of antagonists of GPR17 is a rational goal for elaboration of pharmacotherapies in demyelinating diseases.

References: J Pharmacol Exp Ther. 1992 Sep; 262(3):947-56; Sci Signal. 2013 Oct 22; 6(298):pe34.