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• W2022054436 abstract "Abstract The novel analgesic tapentadol combines μ‐opioid receptor agonism and noradrenaline reuptake inhibition in a single molecule and shows potent analgesia in various rodent models of pain. We analyzed the contribution of opioid and monoaminergic mechanisms to the activity of tapentadol in rat models of nociceptive and neuropathic pain. Antinociceptive efficacy was inferred from tail withdrawal latencies of experimentally naive rats using a tail flick test. Antihypersensitive efficacy was inferred from ipsilateral paw withdrawal thresholds toward an electronic von Frey filament in a spinal nerve ligation model of mononeuropathic pain. Dose–response curves of tapentadol (intravenous) were determined in combination with vehicle or a fixed dose (intraperitoneal) of the μ‐opioid receptor antagonist naloxone (1 mg/kg), the α2‐adrenoceptor antagonist yohimbine (2.15 mg/kg), or the serotonin 5‐HT 2A receptor antagonist ritanserin (0.316 mg/kg). Tapentadol showed clear antinociceptive and antihypersensitive effects (>90% efficacy) with median effective dose (ED 50 ) values of 3.3 and 1.9 mg/kg, respectively. While the antinociceptive ED 50 value of tapentadol was shifted to the right 6.4‐fold by naloxone (21.2 mg/kg) and only 1.7‐fold by yohimbine (5.6 mg/kg), the antihypersensitive ED 50 value was shifted to the right 4.7‐fold by yohimbine (8.9 mg/kg) and only 2.7‐fold by naloxone (5.2 mg/kg). Ritanserin did not affect antinociceptive or antihypersensitive ED 50 values of tapentadol. Activation of both μ‐opioid receptors and α2‐adrenoceptors contribute to the analgesic effects of tapentadol. The relative contribution is, however, dependent on the particular pain indication, as μ‐opioid receptor agonism predominantly mediates tapentadol's antinociceptive effects, whereas noradrenaline reuptake inhibition predominantly mediates its antihypersensitive effects." @default.
• W2022054436 created "2016-06-24" @default.
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• W2022054436 date "2010-09-01" @default.
• W2022054436 modified "2023-10-18" @default.
• W2022054436 title "Differential contribution of opioid and noradrenergic mechanisms of tapentadol in rat models of nociceptive and neuropathic pain" @default.
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• W2022054436 doi "https://doi.org/10.1016/j.ejpain.2010.05.005" @default.
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