Antinociceptive and other behavioral effects of the steroid SC17599 are mediated by the mu-opioid receptor

The objective of the present investigation was to evaluate the behavioral effects of SC17599 (17alpha-acetoxy-6-dimethylaminomethyl-21-fluoro-3-ethoxypregna -3, 5-dien-20-one) in mice and to determine if these effects are selectively mediated by opioid receptors. Although less potent than morphine, SC17599 produced dose-dependent antinociception in both the acetic acid-induced writhing and warm water tail-withdrawal assays. Pretreatment with the opioid antagonist naltrexone and the noncompetitive mu-opioid receptor-selective antagonist methocinnamox, but not the delta-opioid receptor-selective antagonist naltrindole or the kappa-opioid receptor-selective antagonist nor-binaltorphimine, antagonized the antinociceptive effects of both SC17599 and morphine. Similarly to morphine, administration of SC17599 induced the Straub tail response in a dose-dependent and naltrexone-sensitive manner. At the highest doses studied, unlike morphine, SC17599 did not alter locomotor activity. The steroid SC17599 is structurally a very unusually selective mu-opioid agonist that produces behavioral effects, which are similar, but not identical, to those of morphine.