(E)-(±)-2-AMINO-4-METHYL-5-PHOSPHONO-3-PENTENOIC ACID

In the hippocampal slice in vitro, CGP 37849 selectively and reversibly antagonizes NMDA-evoked increases in CA1 pyramidal cell firing rate. In slices bathed in medium containing low Mg ²⁺ levels, concentrations of CGP 37849 up to 10 μM suppresses burst firing evoked in CA1 neurones by stimulation of Schaffer collateral-commissural fibres without affecting the magnitude of the initial population spike.

CGP 37849 potently ( K _i of 220 nM) and competitively inhibits NMDA-sensitive l-[ ³ H]-glutamate binding to postsynaptic density (PSD) fractins from rat brain. CGP 37849 inhibits the binding of the selective NMDA receptor antagonist, [ ³ H]-(±)-3-(2-carboxypiperazin-4-yl)propyl-1-phosphonate (CPP), with a K _i of 35 nM.
In vivo, oral administration to rats of CGP 37849 selectively blocks firing in hippocampal neurones induced by ionophoretically-applied NMDA, without affecting the responses to quisqualate or kainate.
Oral administration to mice of CGP 37849 suppresses maximal electroshock-induced seizures in mice with an ED ₅₀ of 21 mg/kg.