Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0162473 (Frey)
 2,599 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The novel analgesic tapentadol combines mu-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 mu-opioid receptor antagonist naloxone (1mg/kg), the alpha2-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 (21.2mg/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 (5.2mg/kg). Ritanserin did not affect antinociceptive or antihypersensitive ED(50) values of tapentadol. Activation of both mu-opioid receptors and alpha2-adrenoceptors contribute to the analgesic effects of tapentadol. The relative contribution is, however, dependent on the particular pain indication, as mu-opioid receptor agonism predominantly mediates tapentadol's antinociceptive effects, whereas noradrenaline reuptake inhibition predominantly mediates its antihypersensitive effects.
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PMID:Differential contribution of opioid and noradrenergic mechanisms of tapentadol in rat models of nociceptive and neuropathic pain. 2065 10

Tapentadol is a dual action molecule with mu opioid agonist and norepinephrine (NE) reuptake blocking activity that has recently been introduced for the treatment of moderate to severe pain. The effects of intraperitoneal (i.p.) morphine (10mg/kg), tapentadol (10 or 30 mg/kg) or duloxetine (30 mg/kg), a norepinephrine/serotonin (NE/5HT) reuptake inhibitor, were evaluated in male, Sprague-Dawley rats with spinal nerve ligation (SNL) or sham surgery. Additionally, the effects of these drugs on spinal cerebrospinal fluid (CSF) NE levels were quantified. Response thresholds to von Frey filament stimulation decreased significantly from baseline in SNL, but not sham, operated rats. Duloxetine, tapentadol and morphine produced significant and time-related reversal of tactile hypersensitivity. Duloxetine significantly increased spinal CSF NE levels in both sham and SNL rats and no significant differences were observed in these groups. Tapentadol (10 mg/kg) produced a significant increase in spinal NE levels in SNL, but not in sham, rats. At the higher dose (30 mg/kg), tapentadol produced a significant increase in spinal CSF NE levels in both SNL and sham groups; however, spinal NE levels were elevated for an extended period in the SNL rats. This could be detected 30 min following tapentadol (30 mg/kg) in both sham and SNL groups. Surprisingly, while the dose of morphine studied reversed tactile hypersensitivity in nerve-injured rats, CSF NE levels were significantly reduced in both sham- and SNL rats. The data suggest that tapentadol elicits enhanced elevation in spinal NE levels in a model of experimental neuropathic pain offering a mechanistic correlate to observed clinical efficacy in this pain state.
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PMID:Opioid and noradrenergic contributions of tapentadol in experimental neuropathic pain. 2412 Oct 47