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Antinociceptive responses to meptazinol, morphine and oxotremorine and the effects of pretreatment with naloxone or scopolamine on these responses in mice and rats, were examined. 2 Meptazinol evoked larger increases in nociceptive thresholds in the mouse than in the rat, whereas morphine induced large increases in both species. Oxotremorine was both a more potent and a more effective antinociceptive agent in the mouse than in the rat. 3 Antinociceptive responses to meptazinol were consistently inhibited in animals pretreated with naloxone, whereas scopolamine attenuated the effects of meptazinol in some, particularly the mouse tail immersion test, but not in all of the procedures used. 4 Naloxone inhibited all antinociceptive responses to morphine, and scopolamine inhibited all responses to oxotremorine. However, there was no significant interaction between naloxone and oxotremorine or between scopolamine and various opioid analgesic agents. 5 These results indicate that meptazinol, unlike established opioid drugs, may induce antinociception by a dual action on opiate and cholinergic mechanisms.

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Of a variety of non-steroidal anti-inflammatory drugs administered concurrently with meptazinol (p.o.), only ibuprofen potentiated the antinociceptive response (mouse, hot-plate test) to the opioid. In addition, the brain tritium concentration of mice given [3H]meptazinol (p.o. or i.v.) was significantly raised by the oral administration of ibuprofen. It is argued that the interaction between these drugs is pharmacokinetic in nature, due probably to an action of ibuprofen on the biotransformation of meptazinol.

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