Meptazinol cross-tolerance studies between morphine or oxotremorine.

The time course of the development of auto-tolerance to meptazinol as determined by combined heat and pressure nociceptive tests has been examined using two dose levels of meptazinol (10 mg and 30 mgkg-1s.c.) corresponding to the partial agonist and cholinergic components respectively. In mice treated twice daily with meptazinol for eight days, there was cross tolerance to morphine in both tests at each dose level of meptazinol. In chronic morphine treated mice challenged with meptazinol (30 mg kg-1 s.c.), there was no cross tolerance with morphine since meptazinol still retained its antinociceptive effects in both tests. Mice treated chronically with meptazinol (30 mgkg-1 s.c.) did not respond to the cholinomimetic agent oxotremorine, implying that there was cross tolerance between these two analgesics. These data suggest the existence of a one-way tolerance between morphine and meptazinol whilst at higher doses of meptazinol a full tolerance occurs with oxotremorine.