Abstract:
:A new compound, 3-((+/-)-2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP), has been evaluated as an excitatory amino acid receptor antagonist using electrophysiological assays and radioligand binding. In autoradiographic preparations, CPP reduces L-[3H]glutamate binding in regions of the hippocampus rich in N-methyl-D-aspartate (NMDA) receptors, but not in regions rich in kainate sites. In isolated membrane fraction preparations, CPP displaces L-[3H]glutamate binding to NMDA sites, but does not compete with the binding of selective kainate or quisqualate site ligands. CPP potently reduces depolarizations produced by application of NMDA but not depolarizations produced by quisqualate or kainate. Its order of potency against excitatory amino acid-induced responses in the hippocampus is NMDA greater than homocysteate greater than aspartate greater than glutamate greater than kainate greater than or equal to quisqualate. CPP has no effect on lateral perforant path responses or on inhibition of these responses by 2-amino-4-phosphonobutyrate. Finally, at doses that do not affect Schaffer collateral synaptic transmission, CPP reversibly blocks the induction of long-term potentiation of Schaffer synaptic responses. This new compound is, therefore, a highly selective brain NMDA receptor blocker, and the most potent such by nearly an order of magnitude.
journal_name
Brain Resjournal_title
Brain researchauthors
Harris EW,Ganong AH,Monaghan DT,Watkins JC,Cotman CWdoi
10.1016/0006-8993(86)90128-9subject
Has Abstractpub_date
1986-09-10 00:00:00pages
174-7issue
1eissn
0006-8993issn
1872-6240pii
0006-8993(86)90128-9journal_volume
382pub_type
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