Action of 3-((±)-2-carboxypiperazin-4-yl)-propyl-1-phosphonic aci (CPP)

a new and highly potent antagonist of N-methyl-d-aspartate receptors in the hippocampus

Eric W. Harris, Alan H. Ganong, Daniel T Monaghan, Jeffrey C. Watkins, Carl W. Cotman

Research output: Contribution to journalArticle

106 Citations (Scopus)

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]glutama binding in regions of the hippocampus rich in N-methyl-d-aspartate (NMDA) receptors, but not in regions richin 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 > homocysteate > aspartate > glutamate > quisqualate. CPP has no efect 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 synpatic transmission, CPP reversibly blocks the induction of long-term potentiation of Schaffer synaptic responses. This new compounds is, therefore, a higly selective brain NMDA receptor blocker, and the most potent such by nearly an order of magnitude.

Original languageEnglish (US)
Pages (from-to)174-177
Number of pages4
JournalBrain Research
Volume382
Issue number1
DOIs
StatePublished - Sep 10 1986

Fingerprint

Hippocampus
Quisqualic Acid
Aspartic Acid
Kainic Acid
Glutamic Acid
Perforant Pathway
Excitatory Amino Acid Antagonists
Radioligand Assay
Excitatory Amino Acids
Long-Term Potentiation
Glutamate Receptors
aspartic acid receptor
3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid
Ligands
Membranes
Brain

Keywords

  • 3-(±)-2-Carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP)
  • Glutamate
  • Hippocampus
  • Long-term potentiation
  • N-Methyl-d-aspartate (NMDA)
  • Receptor

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology

Cite this

Action of 3-((±)-2-carboxypiperazin-4-yl)-propyl-1-phosphonic aci (CPP) : a new and highly potent antagonist of N-methyl-d-aspartate receptors in the hippocampus. / Harris, Eric W.; Ganong, Alan H.; Monaghan, Daniel T; Watkins, Jeffrey C.; Cotman, Carl W.

In: Brain Research, Vol. 382, No. 1, 10.09.1986, p. 174-177.

Research output: Contribution to journalArticle

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