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Development of a bioavailable μ opioid receptor (MOPr) agonist, δ opioid receptor (DOPr) antagonist peptide that evokes antinociception without development of acute tolerance.

Abstract：

:We have previously described a cyclic tetrapeptide, 1, that displays μ opioid receptor (MOPr) agonist and δ opioid receptor (DOPr) antagonist activity, a profile associated with a reduced incidence of opioid tolerance and dependence. Like many peptides, 1 has poor bioavailability. We describe here an analogue of 1 with an added C-terminal β-glucosylserine residue, Ser(β-Glc)NH2, a modification that has previously been shown to improve bioavailability of opioid peptides. The resulting peptide, 4, exhibits full antinociceptive efficacy in the mouse warm water tail withdrawal assay after intraperitoneal administration with potency similar to that of morphine. Further, 4 does not give rise to acute tolerance and thus represents a promising lead for the development of opioid analgesics with reduced side effects.

journal_name

J Med Chem

journal_title

Journal of medicinal chemistry

authors

Mosberg HI,Yeomans L,Anand JP,Porter V,Sobczyk-Kojiro K,Traynor JR,Jutkiewicz EM

doi

10.1021/jm5002088

subject

Has Abstract

pub_date

2014-04-10 00:00:00

pages

3148-53

issue

7

eissn

0022-2623

issn

1520-4804

journal_volume

57

pub_type

杂志文章

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