A prodrug of NMDA/Glycine site antagonist, L-703,717, with improved BBB permeability: 4-Acetoxy derivative and its positron-emitter labeled analog

T. Haradahira, M. R. Zhang, J. Maeda, T. Okauchi, T. Kida, K. Kawabe, S. Sasaki, T. Suhara, K. Suzuki

Research output: Contribution to journalArticlepeer-review

23 Citations (Scopus)

Abstract

4-Acetoxy derivative (1) of L-703,717, a high-affinity (IC50=4.5 nM) antagonist for the glycine site of NMDA receptors, was synthesized and its brain uptake was examined using a carbon-11 labeled analog ([11C]1). Initial radioactivity in the brain after intravenous injection of [11C]1 was a 2-fold that of [11C]L-703,717 in mice. Rapid bioconversion of [11C]1 into [11C]L-703,717 was demonstrated by metabolite analyses of rat brain after [11C]1 injection. Ex vivo autoradiography of [11C]1 in rat brain showed the same cerebellar localization of radioactivity as [11C]L-703,717. These results indicate that 1 is a promising pharmacological tool as a prodrug of L-703,717 with improved BBB permeability.

Original languageEnglish
Pages (from-to)147-150
Number of pages4
JournalChemical and Pharmaceutical Bulletin
Volume49
Issue number2
DOIs
Publication statusPublished - 2001
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Chemistry(all)
  • Drug Discovery

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