Pharmacokinetic evidence for the long-lasting effect of nor-binaltorphimine, a potent kappa opioid receptor antagonist, in mice

Shiroh Kishioka, Norikazu Kiguchi, Yuka Kobayashi, Chizuko Yamamoto, Fumihiro Saika, Naoki Wakida, Mei Chuan Ko, James H. Woods

Research output: Contribution to journalArticle

14 Scopus citations

Abstract

Nor-binaltorphimine (nor-BNI) is kappa opioid receptor (KOR) antagonist with the extremely long duration in mice analgesic assay, in vivo. For the evaluation of long-lasting effect of nor-BNI, brain content and serum concentration of nor-BNI were quantified in comparison with those of naloxone (a short-acting non-specific opioid receptor antagonist) by high-performance liquid chromatography with electrochemical detector in mice. After concomitant administration (20. mg/kg, s.c.) of nor-BNI and naloxone, nor-BNI in brain and serum showed biphasic elimination, with a rapid phase for 0.75-4. h and a slow phase for 4-48. h. Elimination rate in brain was slower than that of serum. Naloxone in brain and serum was detected for 3. h and 4. h, respectively. The brain/serum ratio of nor-BNI gradually increased over 0.75-48. h, while that of naloxone rapidly declined. After concomitant administration (30. mg/kg, s.c.) of nor-BNI and naloxone, brain nor-BNI was detected in all mice from day 1 to day 21 and in two of six mice at day 28, while serum nor-BNI was detected in all mice at day 1, three of seven at day 3 and one of six at day 7. After that, serum nor-BNI was not detected. Naloxone in brain and serum was not detected at day 1. These results provide pharmacokinetic support for the long-lasting antagonistic effects of nor-BNI.

Original languageEnglish (US)
Pages (from-to)98-102
Number of pages5
JournalNeuroscience Letters
Volume552
DOIs
StatePublished - Jul 2013
Externally publishedYes

Keywords

  • Brain content
  • HPLC-ECD
  • Naloxone
  • Nor-BNI
  • Pharmacokinetics

ASJC Scopus subject areas

  • Neuroscience(all)

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