Articles: narcotic-antagonists.
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Behavioural pharmacology · Dec 2003
Enhanced sensitivity to the antinociceptive effects of kappa opioids in naltrexone-treated rats: dose- and time-dependent effects.
The purpose of the present study was to examine sensitivity to the antinociceptive effects of kappa opioids during chronic treatment with the nonselective opioid antagonist naltrexone. In a warm-water tail-withdrawal procedure, rats were restrained and the latencies to remove their tails from water maintained at 50 and 55 degrees C were recorded. Prior to chronic treatment, spiradoline, U50,488 and (-)-pentazocine produced dose-dependent increases in tail-withdrawal latencies at both 50 and 55 degrees C. ⋯ Enhanced sensitivity was also observed to the antinociceptive effects of U50,488 and (-)-pentazocine when tested 48 h after chronic treatment with 30 mg/kg naltrexone. After termination of chronic treatment, sensitivity to the antinociceptive effects of spiradoline, U50,488 and (-)-pentazocine returned to that originally observed prior to naltrexone treatment. These data indicate that chronic naltrexone treatment enhances sensitivity to the antinociceptive effects of kappa opioids, and that this effect is both dose and time dependent.
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Neuroscience letters · Nov 2003
Randomized Controlled Trial Comparative Study Clinical TrialDose ratio is important in maximizing naloxone enhancement of nalbuphine analgesia in humans.
The analgesic effect of kappa partial agonist opioids (i.e. nalbuphine, pentazocine and butorphanol) is significantly greater in women. Recent evidence suggests that this sexual dimorphism may result from a naloxone-sensitive anti-analgesic effect that is activated along with, and summates with, the analgesic effect of these agents, resulting in decreased analgesia or increased pain. For example, nalbuphine (5 mg) produces profound anti-analgesia (i.e. enhanced pain) in men, but addition of a low dose of the opioid receptor antagonist naloxone (0.4 mg, opioid antagonist) induces significant analgesia in men and enhances nalbuphine analgesia in women. ⋯ In the current study, we tested the hypothesis that an important determinant of naloxone enhancement of nalbuphine analgesia is the dose ratio of nalbuphine to naloxone. Since a dose ratio of 12.5:1 (i.e. 5 mg nalbuphine:0.4 mg naloxone) resulted in analgesic enhancement, but a dose ratio of 6.25:1 (2.5 mg:0.4 mg) did not, we tested the same, lower, dose of nalbuphine (2.5 mg) in combination with a lower dose of naloxone (0.2 mg) to maintain the 12.5:1 dose ratio. This lower dose of naloxone significantly prolonged the analgesic effect of nalbuphine in both men and women, suggesting that the anti-analgesic effect of nalbuphine is present in both sexes at the 2.5 mg dose and that the dose ratio of nalbuphine to naloxone is an important determinant of the analgesic efficacy of this combination.
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Randomized Controlled Trial Comparative Study Clinical Trial
Naloxone provokes similar pain facilitation as observed after short-term infusion of remifentanil in humans.
In contrast to an expected preventive analgesic effect, clinical observations suggest that intraoperatively applied opioids can induce postoperative hyperalgesia. We tested the development of post-infusion hyperalgesia in a newly developed experimental model of electrically induced pain and secondary mechanical hyperalgesia. In a double-blind, placebo controlled, cross-over study, 13 subjects received either saline placebo, remifentanil (0.05 or 0.1 microg/kg/min) or naloxone (0.01 mg/kg). ⋯ Naloxone infusion similarly resulted in increased pain (anti-analgesia) (p<0.001) and mechanical hyperalgesia (p<0.01). Increased pain ratings following withdrawal of remifentanil significantly correlated to anti-analgesia evoked by the mu-opioid antagonist naloxone (p<0.01) and was of similar magnitude, suggesting inhibition of endogenous opioids as an underlying mechanism. In contrast, hyperalgesia after remifentanil was more pronounced than hyperalgesia after naloxone administration and did not correlate to the observed anti-analgesic effects, suggesting the involvement of additional receptors systems other than the endorphin system.
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Letter Randomized Controlled Trial Clinical Trial
Prophylactic epidural naloxone reduces the incidence and severity of neuraxial fentanyl-induced pruritus during labour analgesia in primiparous parturients.