Analgesic and Antiinflammatory Effects of Two Novel κ-Opioid Peptides

Abstract

FE 200665 is a peripherally selective kappa-agonist with potent analgesic and antiinflammatory properties that may lead to improved analgesic-antiinflammatory therapy compared with centrally acting opioids or standard nonsteroidal antiinflammatory drugs.

Modulation of Peripheral Sensory Neurons by the Immune System: Implications for Pain Therapy

“…In fact, several studies indicate that a large proportion (50-100%) of the analgesic effects produced by systemically administered conventional opioids can be mediated by peripheral opioid receptors (Craft et al, 1995;Binder et al, 2001;Reichert et al, 2001;Lewanowitsch and Irvine, 2002;Shannon and Lutz, 2002;Fü rst et al, 2005;Labuz et al, 2007;Gaveriaux-Ruff et al, 2011). For example, in a rat model of urinary bladder inflammation, the peripherally restricted antagonist naloxone methiodide attenuated the antinociceptive effects of systemically applied -and -receptor agonists by 50% and fully abolished the effects of a ␦-agonist (Craft et al, 1995).…”

Novel κ-opioid receptor agonist MB-1C-OH produces potent analgesia with less depression and sedation

“…With the [ 35 S]GTPγS binding assay, a classical functional measurement for receptor activation that can be used to determine the potencies and efficacies of opioid ligands at opioid receptors [25] , we found that MB- It have been well demonstrated that κ-agonists produce potent antinociception in different animal pain models [9,[11][12][13] . Our findings were similar to these studies in that we found that MB-1C-OH produced a significant antinociceptive effect in the acetic acid-induced writhing test via κ-but not µ-or δ-opioid receptors.…”

“…The precise mechanisms of MB-1C-OH-induced antinociception are of great interest and need to be elucidated in future studies. Many recent studies have shown that κ-opioid agonists produced analgesic effect via peripheral κ-opioid receptor [9][10][11][12][13] without producing undesirable side effects.…”

“…Increasing evidence from a wide variety of visceral pain models, inflammatory pain models and thermal hyperalgesia induced by capsaicin show that κ-opioid agonists could produce their analgesic effects via peripheral targeting [9][10][11][12][13] . Thus, peripherally acting κ-opioid agonists may be more promising candidate pharmacotherapies for pain relief because they do not cause central nervous system side effects.…”

Gene therapy for pancreatitis pain

“…[44][45][46][47][48][49] The local administration of m-and d-opioid receptor agonists, at doses that show no systemic effect, has been shown to decrease plasma extravasation during peripheral inflammation. 45 These effects are induced by activation of opioid receptors located in both the central and peripheral nervous systems.…”