MISC

2000年

A strategy for increasing the brain uptake of a radioligand in animals: Use of a drug that inhibits plasma protein binding

Nuclear Medicine and Biology
  • Terushi Haradahira
  • ,
  • Ming-Rong Zhang
  • ,
  • Jun Maeda
  • ,
  • Takashi Okauchi
  • ,
  • Kouichi Kawabe
  • ,
  • Takayo Kida
  • ,
  • Kazutoshi Suzuki
  • ,
  • Tetsuya Suhara

27
4
開始ページ
357
終了ページ
360
記述言語
英語
掲載種別
DOI
10.1016/S0969-8051(00)00096-2
出版者・発行元
Elsevier Inc.

A positron-emitter labeled radioligand for the glycine-binding site of the N-methyl-D-aspartate (NMDA) receptor, [11C]L-703,717, was examined for its ability to penetrate the brain in animals by simultaneous use with drugs having high-affinity separate binding sites on human serum albumin. [11C]L-703,717 has poor blood-brain barrier (BBB) permeability because it binds tightly to plasma proteins. Co-injection of warfarin (50-200 mg/kg), a drug that binds to albumin and resembles L-703,717 in structure, dose-dependently enhanced the penetration by [11C]L-703,717 in mice, resulting in a five-fold increase in the brain radioactivity at 1 min after the injection. Drugs structurally unrelated to L-703,717, salicylate, phenol red, and L-tryptophan, were less effective or ineffective in increasing the uptake of [11C]L-703,717. These results suggest that the simultaneous use of a drug that inhibits the binding of a radioligand to plasma proteins is a useful way to overcome the poor BBB permeability of the radioligand triggered by its tight binding to plasma proteins. In brain distribution studies in rodents, it was found that, after the increase in brain uptake with warfarin, much of the glycine site antagonist accumulates in the cerebellum but its pharmacological specificity did not match the glycine site of NMDA receptors. © 2000 Elsevier Science Inc. All rights reserved.

リンク情報
DOI
https://doi.org/10.1016/S0969-8051(00)00096-2
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/10938470
ID情報
  • DOI : 10.1016/S0969-8051(00)00096-2
  • ISSN : 0969-8051
  • PubMed ID : 10938470
  • SCOPUS ID : 0034182879

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