Stereospecific reversal of nitrous oxide analgesia by naloxone

The opiate antagonist naloxone was found to block nitrous oxide analgesia in a stereospecific fashion. Using a modified hotplate test in mice, the (−)-enantiomer of naloxone (which has a K D of ≈ 1 nM for opiate receptors) antagonized the analgesic actions of nitrous oxide in a dose-dependent (2.5–20 mg/kg) fashion. In contrast, the (+)-enantiomer (K D ≈ 10,000 nM) had no effect on nitrous oxide analgesia at the highest dose tested (40 mg/kg). These data strongly suggest that nitrous oxide analgesia is mediated via opiate receptors and is consistent with the hypotheses that this effect occurs either through the release of endogenous opioids or by physical perturbation of the opiate receptors.