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Antinociceptive profile of potent opioid peptide AM94, a fluorinated analogue of biphalin with non‐hydrazine linker
Author(s) -
Mollica Adriano,
Costante Roberto,
Stefanucci Azzurra,
Pinnen Francesco,
Lucente Gino,
Fidanza Stefano,
Pieretti Stefano
Publication year - 2013
Publication title -
journal of peptide science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.475
H-Index - 66
eISSN - 1099-1387
pISSN - 1075-2617
DOI - 10.1002/psc.2465
Subject(s) - analgesic , chemistry , linker , potency , opioid , morphine , pharmacology , tail flick test , in vivo , nociception , peptide , opioid receptor , opioid peptide , stereochemistry , receptor , in vitro , medicine , biochemistry , microbiology and biotechnology , computer science , biology , operating system
AM94 is a fluorinated analog of biphalin with non‐hydrazine linker that has an in vitro affinity for μ‐opioid and δ‐opioid receptors tenfold higher than biphalin. Furthermore, in vivo evaluation in rats showed that AM94 has in hot plate test – after both intracerebroventricular and intravenous administrations – a greater and more durable efficacy than biphalin. Here, the antinociceptive profile of AM94 is further evaluated by following two different administration routes, intrathecal and subcutaneous, and two different animal species, rats and mice. The analgesic potency of AM94 is compared with that of both the parent peptide biphalin and morphine. Results show that in rats (tail flick test) and in mice (formalin test), AM94 has a higher and more durable analgesic effect than biphalin after intrathecal and subcutaneous administrations. Conformational properties of biphalin and AM94 were also investigated by variable‐temperature 1 H NMR and energy minimization. Copyright © 2012 European Peptide Society and John Wiley & Sons, Ltd.