Glycopeptide enkephalin analogues produce analgesia in mice: Evidence for penetration of the blood-brain barrier

Robin Polt, Frank Porreca, Lajos Z. Szabò, Edward J. Bilsky, Peg Davis, Thomas J. Abbruscato, Thomas P. Davis, Robert Horvath, Henry I. Yamamura, Victor J. Hruby

Research output: Contribution to journalArticle

235 Scopus citations

Abstract

Most peptides have not proved useful as neuroactive drugs because they are blocked by the blood-brain barrier and do not reach their receptors within the brain. Intraperitoneally administered L-serinyl β-D-glucoside analogues of [Met5]enkephalin (glycopeptides) have been shown to be transported across the blood-brain barrier to bind with targeted μ- and δ-opioid receptors in the mouse brain. The opioid nature of the binding has been demonstrated with intracerebroventricularly administered naloxone. Paradoxically, glucosylation decreases the lipophilicity of the peptides while promoting transport across the lipophilic endothelial layer. It is suggested that glucose transporter GLUT-1 is responsible for the transport of the peptide message. Profound and long-lasting analgesia has been observed in mice (tail-flick and hot-plate assays) with two of the glycopeptide analogues when administered intraperitoneally.

Original languageEnglish (US)
Pages (from-to)7114-7118
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume91
Issue number15
DOIs
StatePublished - Jul 19 1994

Keywords

  • antinociception
  • drug delivery
  • glucosides
  • opioid receptor
  • peptides

ASJC Scopus subject areas

  • General

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