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.
Hatta
K
K
Department of Psychopharmacology, Psychiatric Research Institute of Tokyo, Japan.
Yamamato
T
T
Hori
T
T
Okuwa
M
M
Moroji
T
T
D000818:Animals; D066298:In Vitro Techniques; D007473:Ion Channels / Q000187:drug effects*; D008274:Magnesium / Q000378:metabolism*; D008297:Male; D010622:Phencyclidine / Q000031:analogs & derivatives / Q000378:metabolism; D010879:Piperazines / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D017470:Receptors, Glutamate; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects*; D017981:Receptors, Neurotransmitter / Q000187:drug effects*; D017478:Receptors, Phencyclidine
D007473:Ion Channels; D010879:Piperazines; D017470:Receptors, Glutamate; D016194:Receptors, N-Methyl-D-Aspartate; D017981:Receptors, Neurotransmitter; D017478:Receptors, Phencyclidine; C012058:tenocyclidine; C050592:3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid; D008274:Magnesium; D010622:Phencyclidine