Effects of U-50488H, a selective kappa-analgesic, on the minimum anesthetic concentration (MAC) of halothane in the rat.

Abstract

The effects of U-50488H, a selective kappa-analgesic, on the minimum anesthetic concentration (MAC) of an inhalational agent (halothane) were studied in the rat. U-50488H was given subcutaneously in doses of 3, 10, and 30 mg/kg body weight. The maximal MAC reduction was about 60%. The potency ratio of U-50488H to morphine in this model was comparable with potency ratios in other analgesic assays. In separate experiments, the percent reduction in halothane MAC with U-50488H at 30 mg/kg was determined during the infusion of naloxone (5 micrograms X kg-1 X min-1 and 1 mg X kg-1 X min-1) at doses shown to have reversed a 70% reduction in MAC by 10 mg/kg of morphine. Only when naloxone was infused at 1 mg X kg-1 X min-1 was there a significant reversal of the U-50488H-induced reduction in halothane MAC. This observation suggests that the reduction in MAC of halothane with U-50488H was not mediated by a mu-receptor. In conclusion, through the use of a selective pharmacologic tool that stimulates kappa-receptors we have demonstrated potential utility of kappa-analgesics as supplements to general anesthesia.