After the
intravenous injection of
butorphanol or
norbutorphanol in rats every 1 hr for 3 days,
naloxone-induced
body weight loss and withdrawal syndrome were observed to some degree. A slow-released
emulsion containing each of the test drugs was injected subcutaneously in guinea-pigs, and
naloxone was administered after 2 or 3 days. BT caused little jumping response even at a dose of 600 mg/kg, and the reaction was significantly weaker than that of
pentazocine. No jumping responses were recognized in the cases of NB (600 mg/kg). In morphinized rats, the injection of BT or HB caused potent
body weight loss, and these rats exhibited withdrawal syndrome which was more potent than that by
pentazocine at the same dose. The
body weight losses by the injection of NB and
pentazocine were to the same degree, and these changes were significantly different from that of the saline control. BT inhibited the
adenylate cyclase activity of the rat caudate nuclei, and the effect was weaker than that of
pentazocine. NB showed a slight inhibition, and HB had no effect on the activity. These results suggest that the physical dependence liability of
butorphanol is less than that of
pentazocine, and the potent mu-antagonistic character of
butorphanol is based on the liability. NB, a mu-agonist, makes dependence production possible. The ability of HB is negligible.