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

Eur J Pharmacol. 2000 Apr 28;395(2):121-8. doi: 10.1016/s0014-2999(00)00176-x.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acetic Acid
  • Analgesics / metabolism
  • Analgesics / pharmacology*
  • Animals
  • Hot Temperature
  • Male
  • Mice
  • Motor Activity / drug effects
  • Pain Measurement
  • Pain* / chemically induced
  • Pain* / physiopathology
  • Pregnadienes / pharmacology*
  • Receptors, Opioid, mu / drug effects
  • Receptors, Opioid, mu / metabolism*

Substances

  • Analgesics
  • Pregnadienes
  • Receptors, Opioid, mu
  • SC 17599
  • Acetic Acid