European journal of pharmacology
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We recently characterized a novel bifunctional agonist for opioid and neuropeptide FF receptors, named BN-9, which exhibited potent analgesia in the mouse tail-flick test when given centrally. To further evaluate its potential therapeutic efficacy for translational-medical development, the current work was performed to explore the antinociceptive activities of intraperitoneal (i.p.) administration of BN-9 in mouse models of tail-flick assay, formalin pain, visceral pain and post-operative pain. In the tail-flick test, BN-9 induced a dose-related antinociceptive effect, which was fully blocked by systemic pretreatment with the peripheral acting opioid receptor antagonist naloxone methiodide, but not supraspinal naloxone methiodide, implying the involvement of the peripheral opioid receptors. ⋯ Compared with morphine, intraperitoneal administration of BN-9 exerted less inhibition of gastrointestinal transit. These data show that BN-9 induced systemic analgesia with reduced side-effects on tolerance and constipation. This article suggests that systemic injection of BN-9 causes effective antinociception in different preclinical pain models via the peripheral opioid receptors, providing an attractive approach to develop peripherally acting opioid analgesics with multiple targeting properties.