Pharmacological action of eptazocine (l-1,4-dimethyl-10-hydroxy-2,3,4,5,6,7-hexahydro-l,6-methano-lH-4-benzazonine). (IV) Narcotic agonist and antagonist-actions of eptazocine

It was investigated whether the analgesic effects of eptazocine were antagonized by treatment with naloxone, one of the opiate antagonists, and whether morphine-induced effects were affected by eptazocine. The analgesic effects of eptazocine, similar to those of morphine, were completely antagonized by treatment with 0.5 mg/kg naloxone, s.c, as determined by the hot plate and pressure methods in mice and by the tail-flick method in rats. In contrast, as tested by the acetic acid-induced writhing method in mice, the analgesic effect of eptazocine, similar to that of pentazocine, was not antagonized by treatment with 1.0 mg/kg naloxone, s.c, while that of morphine was antagonized by 0.5 mg/kg naloxone, s.c. Using the acetic acid-induced writhing method in mice, the pA2 values of naloxone were found to be the following order: eptazocine <pentazocine< morphine. In addition, the analgesic effect of morphine was dose-dependently antagonized by the treatment with eptazocine as determined by the pressure method. Furthermore, the stimulating effect of morphine on spontaneous locomotor activity was also antagonized by eptazocine. These results suggest that eptazocine may be classified as one of the opiate agonist-antagonists.