3-((+/-)2-carboxypiperazin-4-yl)propyl-1-phosphonic acid (CPP) more potently antagonizes the high-affinity Mg2+ binding site on the N-methyl-D-aspartate/phencyclidine receptor ion channel complex than the L-glutamate recognition site.

Using frozen-thawed and extensively washed rat cortical membranes, the effects of 3-((+/-)2-carboxypiperazin-4-yl)propyl-1-phosphonic acid (CPP) on [3H]N-(1-[2-thienyl]cyclohexyl)-3,4-piperidine ([3H]TCP) binding stimulated by either 1 microM L-glutamate or 300 microM Mg2+ were examined. CPP much more potently inhibited Mg(2+)-stimulated [3H]TCP binding than [3H]TCP binding stimulated by L-glutamate, suggesting that CPP preferentially acts at Mg2+ recognition sites with high affinity, which may be anatomically and/or functionally associated with a recognition site for N-methyl-D-asparate (NMDA) antagonists.