Comparative pharmacological and biochemical studies between butorphanol and morphine.

A number of in vivo and in vitro studies were undertaken to compare the pharmacological and biochemical effects of the partial agonist, butorphanol, with that of morphine. Both compounds were equipotent antinociceptive agents in the rat tail withdrawal test. In the acetic acid writhing test butorphanol had approximately 3.5 times the antiwrithing activity on a molar basis than morphine. In a study of the effects of these compounds on body temperature, butorphanol as well as morphine produced hyperthermia after acute dosing. Additionally, butorphanol produced a profound diuresis and decrease in urine osmolality after acute administration. In contrast, morphine produced an antidiuresis throughout most of the study period with no significant changes in urine osmolality from control. Butorphanol administration had no effect on respiratory rate, while morphine markedly decreased respiratory rate. In in vitro radioligand displacement studies, butorphanol was a potent competitor against 3H-DAGO, 3H-DPDPE, and 3H(-)-EKC binding, exhibiting 3, 10, and 30 times more activity, respectively, than morphine. Both compounds were weak inhibitors of 3H-(+)-SKF 10047 binding, yielding IC50 values of in excess of 1 microM. The results indicate that butorphanol has multiple actions on the opioid receptor system, and shares similarities as well as differences in its mechanism(s) of actions with morphine.