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

• Published in: European journal of pharmacology 2000-04, Vol.395 (2), p.121-128
• Main Authors: Houshyar, Hani, Mc Fadyen, Iain J, Woods, James H, Traynor, John R
• Format: Article
• Language: English
• Subjects: Acetic Acid; Analgesics; Analgesics - metabolism; Analgesics - pharmacology; Animals; Antinociception; Biological and medical sciences; Hot Temperature; Locomotor activity; Male; Medical sciences; Mice; Morphine; Motor Activity - drug effects; Mouse; Neuropharmacology; Neurotransmitters. Neurotransmission. Receptors; Pain - chemically induced; Pain - physiopathology; Pain Measurement; Peptidergic system (neuropeptide, opioid peptide, opiates...). Adenosinergic and purinergic systems; Pharmacology. Drug treatments; Pregnadienes - pharmacology; Receptors, Opioid, mu - drug effects; Receptors, Opioid, mu - metabolism; SC17599; Straub tail
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/S0014-2999(00)00176-X

The objective of the present investigation was to evaluate the behavioral effects of SC17599 (17α-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 μ-opioid receptor-selective antagonist methocinnamox, but not the δ-opioid receptor-selective antagonist naltrindole or the κ-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 μ-opioid agonist that produces behavioral effects, which are similar, but not identical, to those of morphine.