Phosphono dipeptides and piperazine derivatives as antagonists of amino acid-induced and synaptic excitation in mammalian and amphibian spinal cord.

Two novel dipeptides, beta-D-aspartylaminomethylphosphonate (Asp-AMP) and gamma-D-glutamylaminomethylphosphonate (Glu-AMP) are potent and selective N-methyl-D-aspartate receptor antagonists and specifically depress polysynaptic excitation in the cat, rat and frog spinal cords. In the same tissues, 1-(p-chlorobenzoyl)-piperazine-2,3-dicarboxylic acid (pCB-PzDA) and some related piperazines, are broader spectrum excitatory amino acid antagonists, showing increased potency as kainate and quisqualate antagonists compared with previously described antagonists of this type. These piperazines are more effective as depressants of monosynaptic than of polysynaptic excitation.