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Effects of U‐50488H, a Selective k‐Analgesic, on the Minimum Anesthetic Concentration (MAC) of Halothane in the Rat

The effects of U-50488H, a selective K-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-5048SH 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 μg·kg−1·min−1 and 1 mg·kg−1·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·kg−1·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 μ-receptor. In conclusion, through the use of a selective pharmacologic tool that stimulates K-receptors we have demonstrated potential utility of K-analgesics as supplements to general anesthesia.