It was investigated whether tolerance to the pharmacological actions and cross-tolerance between eptazocine and pentazocine/morphine were developed by successive administration of eptazocine. In the experiments of mice, successive administration of eptazocine failed to decrease the pharmacological actions of eptazocine on the acetic acid-induced writhing, the pressure and the wheel cage methods. Cross-tolerance between eptazocine and pentazocine/morphine was not observed. Tolerance to the actions of pentazocine and morphine was developed on the wheel cage and the acetic acid-induced writhing/pressure methods, respectively. Cross-tolerance between pentazocine and morphine was also developed on the pressure method. On the tail flick method of rats, tolerance to the action of eptazocine was observed, similar to morphine, but not cross-tolerance between eptazocine and morphine. These results suggest that there is species difference between mice and rats with regard to the ability of tolerance development and that the mechanisms of tolerance development between eptazocine and pentazocine/morphine may be different since eptazocine failed to show cross tolerance to these analgesics.
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