Interaction of analgesics and l-stepholidine
Abstract
l-Stepholidine (SPD), a new dopaminergic antanonist, 50-170 mg/kg ip abolished the righting reflex in mice. The dose-effect relationship appeared to be linear (t=0.996, P<0.01). When dihydroetorphine (DHE, 2 microg/kg, ip) was given in addition, the line shifted to the left. EEG in rabbits changed from low voltage rapid waves to high voltage slow waves. However, the combination of pethidine with SPD did not induce a loss of righting reflex, and the EEG changes were negligible. These results suggest that DHE is synergistic to SPD in inhibiting CNS, while pethidine is not.
In mice, DHE, pethidine and SPD elevated pain threshold (hot plate method) by 90, 163, and 175%, respectively (P<0.01). When used in combination, DHE+SPD or pethidine+SPD raised the pain threshold by 433 or 369% (P<0.01), respectively. The combined actions were greater than the sums of action of those drugs when used alone. This indicates that their analgesic actions are synergistic.
Both DHE and pethidine cuased a slow-down of heart rate and an inhibition of respiration, but SPD did not. These side-efffects of DHE were not abated by SPD.
Keywords:
In mice, DHE, pethidine and SPD elevated pain threshold (hot plate method) by 90, 163, and 175%, respectively (P<0.01). When used in combination, DHE+SPD or pethidine+SPD raised the pain threshold by 433 or 369% (P<0.01), respectively. The combined actions were greater than the sums of action of those drugs when used alone. This indicates that their analgesic actions are synergistic.
Both DHE and pethidine cuased a slow-down of heart rate and an inhibition of respiration, but SPD did not. These side-efffects of DHE were not abated by SPD.