Bicyclic lactones derived from kainic acid as novel selective antagonists of neuroexcitatory amino acids

Ora Goldberg, Alberto Luini, Vivian I. Teichberg

Research output: Contribution to journalArticlepeer-review

Abstract

The bicyclic [2S-(2α,3β,4β)]-2-carboxy-4-(1-hydroxy-1-methylethyl)-3- pyrrolidineacetic acid 5-lactone (4), as well as its 4-[1-hydroxy-1-(iodomethyl)ethyl], 4-[1-hydroxy-1-(hydroxymethyl)ethyl], and 4-[1-hydroxy-1-[(phenylthio)methyl]ethyl] analogues, 6, 7, and 9, respectively, were designed and synthesized as potential selective antagonists of neuroexcitatory amino acids. When applied to rat brain slices, these lactones, which are chemically derived from kainic acid, inhibit the stimulation of Na+ fluxes induced by the neuroexcitants kainic acid and N-methyl-D-aspartic acid. Lactone 4 and the hydroxy lactone 7 block preferentially the response to N-methyl-D-aspartic acid, while the iodo lactone 6 and the phenylthio lactone 9 are mainly kainic acid antagonists. Total inhibitions can be obtained, half of the maximal effect being observed at lactone concentrations in the range of 0.2-3 mM.

Original languageEnglish
Pages (from-to)39-42
Number of pages4
JournalJournal of Medicinal Chemistry
Volume26
Issue number1
Publication statusPublished - 1983

ASJC Scopus subject areas

  • Organic Chemistry

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