Abstract
Introduction: Opioid analgesics are the most efficient and widely used drugs for the management of moderate to severe pain. However, side effects associated with mu receptor activation, such as respiratory depression, tolerance and physical dependence severely limit their clinical application. Currently, the kappa-opioid system is the most attractive in terms of the clinical problem of pain, because kappa-agonists do not cause euphoria and physical dependence. The purpose of this study was to evaluate the antinociceptive effect of the novel compound - RU-1205. Methods: The analgesic activity of RU-1205 was studied on nociceptive models that characterize the central and peripheral pathways of pain sensitivity (hot plate test, electrically induced vocalisation, formalin test, writhing test). Results: RU-1205 exhibited highly potent antinociceptive effects in rodent models of acute pain with ED50 values of 0.002 - 0.49 mg /kg. Pretreatment with the κ-opioid receptor antagonist norBinaltorphimine significantly attenuated the analgesic activity of investigated substance in a hot plate test. Conclusions: It was established that the compound shows a significant dose-dependent central and peripheral analgesic effect. It was assumed kappa-opioidergic mechanism of analgesic effect of RU-1205.
Highlights
Opioid analgesics are the most efficient and widely used drugs for the management of moderate to severe pain
The objective of the present study was to explore the analgesic activity of RU-1205 by methods characterizing nociceptive response at the level of medulla oblongata, peripheral pain and the mechanism of analgesia
In the first phase of formalin test compound RU-1205 injected intraperitoneally at a dose of 0.01, 0.1 and 1 mg/kg decreased the number of flinches by 27%, 39% and 55%, respectively
Summary
Opioid analgesics are the most efficient and widely used drugs for the management of moderate to severe pain. Side effects associated with mu receptor activation, such as respiratory depression, tolerance and physical dependence severely limit their clinical application. The kappa-opioid system is the most attractive in terms of the clinical problem of pain, because kappa-agonists do not cause euphoria and physical dependence. Methods: The analgesic activity of RU-1205 was studied on nociceptive models that characterize the central and peripheral pathways of pain sensitivity (hot plate test, electrically induced vocalisation, formalin test, writhing test). Conclusions: It was established that the compound shows a significant dose-dependent central and peripheral analgesic effect. It was assumed kappa-opioidergic mechanism of analgesic effect of RU-1205. Compounds showing kappa opioid receptor agonist activity can be regarded as substances that lack this undesired effect [5]
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