Synthesis of 11C-labelled bis(phenylalkyl)amines and their in vitro and in vivo binding properties in rodent and monkey brains

Shigeki Sasaki, Fumie Kurosaki, Terushi Haradahira, Fumihiko Yamamoto, Jun Maeda, Takashi Okauchi, Kazutoshi Suzuki, Tetsuya Suhara, Minoru Maeda

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Two new 11C-labelled ligands, N-(3-(4-hydroxyphenyl)propyl)-3- (4-methoxyphenyl)propylamine ([11C]2) and N-(3-(4-hydroxyphenyl) butyl)-3-(4-methoxyphenyl)butylamine ([11C]3) were designed based on bis(phenylalkyl)-amines (1) which have been reported as polyamine site antagonists with high-selectivity for NR1A/2B NMDA receptors, and radiolabelling of the corresponding phenol precursors with [11C]methyl iodide was readily accomplished. The in vitro inhibition experiments using rat brain slices showed that [11C]2 and [11C]3 share the binding sites with spermine and/or ifenprodil but not with CP-101,606, a highly potent NR2B-selective NMDA antagonist, and that divalent cations such as Zn 2+ produced significant inhibition of both [11C]2 and [11C]3 bindings. Intravenous injection of [11C]3 in mice showed almost homogenous distribution throughout the brain. Attempts to block the tracer uptake of [11C]3 by pre-injection with the unlabelled 3 or spermine in rats were unsuccessful, but a small decrease in the cerebral uptake of [11C]3 by co-treatment with the unlabelled 3 was observed in a monkey PET study. The present findings indicate that none of these 11C-labelled analogues have potential for PET study of binding sites on the N-methly-D-aspartate (NMDA) receptors.

Original languageEnglish
Pages (from-to)531-537
Number of pages7
JournalBiological and Pharmaceutical Bulletin
Volume27
Issue number4
DOIs
Publication statusPublished - Apr 1 2004

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Pharmaceutical Science

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