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(1) in children ages 2 to 16 years receiving 10 or 20 mg of omeprazole as a single oral dose, the PK are quite comparable to values reported for adults, and (2) in pediatric patients who are CYP2C19 extensive metabolizers, there was no association between genotype and the pharmacokinetics of omeprazole.

1 The opioid antagonists, naloxone, GPA 2163, levallorphan and Mr-2266 reduced the latency of the jumping reaction of mice in the hot plate test. The (+)-isomers of levallorphan and Mr-2266 which are devoid of antagonistic activity did not increase this latency. 2 In the same nociceptive reaction test, the enhancing effect of naloxone progressed in a dose-range similar to that required for the antagonism by naloxone of the depressive action of morphine. 3 The facilitatory effect of naloxone was not blocked by the previous administration of morphine or etorphine but it was prevented by pretreatment with a high dose of buprenorphine. 4 The antagonism by naloxone of morphine and of buprenorphine did not follow the same pattern. 5 The factors which are or may be involved in the efficacy of naloxone in enhancing nociceptive reactions are discussed. 6 The enhancing effect of naloxone may be due to an antagonism of endogenous ligands for the opiate receptor. If so, these ligands would be involved in reaction to but not in perception of nociceptive stimuli which need not be harmful ones.

In mice with streptozotocin-induced hyperglycemia, nociception was tested after naloxone administration in hot plate and tail immersion tests. The choice of these two tests was to include a supra-spinal nociceptive reflex indicative of higher cognitive process (hot-plate test) as well as a reflex which predominantly represents lower spinal motor mechanisms (tail immersion test). Naloxone-induced hyperalgesia was attenuated in both tests in mice with streptozotocin-induced diabetes. In mice with hyperglycemia induced by intraperitoneal dextrose administration, naloxone hyperalgesia was significantly enhanced in the hot plate test. The basal nociceptive threshold in streptozotocin-treated animals was decreased in the immersion but not in the hot plate test. These results indicate that hyperglycemia per se does not adequately explain the changes in naloxone hyperalgesia in experimental models of diabetes. They also suggest that acute hyperglycemia may modify the interaction of endogenous opioid peptides with their receptors only at supra-spinal sites. However, chronic hyperglycemia appears to affect endogenous opioid peptides both at spinal and supra-spinal levels and their interaction with the opiate receptors.

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Using the hot plate test, the potency and mechanism of the analgesic activity of levonantradol was studied in mice. Levonantradol is 10 to 30 times more potent than morphine; the antinociception can be only partially blocked by naloxone. Similar limited antagonism by cholinergics indicates possible opiodergic mechanism. The role of serotoninergic pathways is unclear; antinociception is partially blocked by 5,7‐dihydroxytryptamine, unaffected by p‐chlorophenylalanine, and potentiated by cyproheptadine. Levonantradol blocks naloxone‐induced signs of abstinence in morphine‐dependent mice, being 3000 times more potent than morphine and 300 times more potent than Δ9‐tetrahydrocannabinol (THC).

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