Premium
In vivo characterization of the antinociceptive effects of UFP‐512 and BG‐156: Selective Delta Opioid Receptor Ligands
Author(s) -
Lopez Alexa,
Balboni Gianfranco,
Martinez Heather,
Giuvelis Denise,
Negus Steve,
Salvadori Severo,
Bilsky Edward J.
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.742.6
Subject(s) - pharmacology , chemistry , in vivo , hyperalgesia , opioid , receptor , nociception , agonist , biochemistry , medicine , biology , microbiology and biotechnology
Delta opioid receptor (DOR) agonists have demonstrated efficacy in several preclinical models of pain. In addition, several groups have demonstrated novel antidepressant and anxiolytic effects for this class of compounds. Modification of the N‐terminal tyrosine by 2',6′‐dimethyl‐L‐tyrosine (Dmt) can have significant effects on opioid peptide affinity, selectivity, and efficacy at the DOR. The studies presented here assess the in vivo activity of two structurally related peptides that possess DOR‐selectivity (UFP‐512 and BG‐156). Both compounds produced dose‐related antinociception in the mouse 55°C tail‐flick assay (i.c.v. A50 values of 8.0 and 5.4 nmol, respectively). I.v. administration of these compounds produced limited antinociception (<20% MPE). In contrast, systemic administration of UFP‐512 produced potent, dose‐related antinociception in the mouse acetic acid writhing assay. In Rhesus monkeys, the intramuscular administration of UFP‐512 dose‐dependently reversed capsaicin‐induced thermal hyperalgesia, with a 10 mg/kg dose producing ~50% reversal. The data indicates that these peptides produce antinociception and antihyperalgesia in both rodents and monkeys, and that systemic injections of the compound may act primarily at peripheral DORs. Additional studies are being conducted to confirm receptor selectivity and site(s) of action in vivo.