161230-88-2

MDL 105519 is a potent and selective ligand for the glycine recognition site that completely inhibit the binding of [ ³ H]glycine to rat brain membranes with a K _i value of 10.9 nM. MDL 105519 is approximately 10,000-fold selective for the glycine recognition site relative to the other receptor types investigated. MDL 105519 inhibits NMDA-dependent responses, such as elevations of [ ³ H]TCP binding in brain membranes, cyclic GMP accumulation in brain slices, and alterations in cytosolic Ca ²⁺ and Na ⁺ -Ca ²⁺ currents in cultured neurons. Inhibition is non-competitive with respect to NMDA and could be nullified with D-serine.

MDL 105519 is an NMDA receptor antagonist in vivo . Intravenously administration of MDL 105519 prevents harmaline-stimulated increases in cerebellar cyclic GMP content, providing biochemical evidence of NMDA receptor antagonism in vivo . This antagonism is associated with anticonvulsant activity in genetically based, chemically induced, and electrically mediated seizure models. Anxiolytic activity is observed in the rat separation-induced vocalization model, but muscle-relaxant activity is apparent at lower doses. Higher doses impair rotorod performance, but are without effect on mesolimbic dopamine turnover or prepulse inhibition of the startle reflex.