Houshyar H, Mc Fadyen I J, Woods J H, Traynor J R
Department of Pharmacology, University of Michigan, Ann Arbor, MI 48109, USA.
Eur J Pharmacol. 2000 Apr 28;395(2):121-8. doi: 10.1016/s0014-2999(00)00176-x.
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.
本研究的目的是评估SC17599（17α-乙酰氧基-6-二甲基氨基甲基-21-氟-3-乙氧基孕甾-3,5-二烯-20-酮）对小鼠的行为影响，并确定这些影响是否由阿片受体选择性介导。尽管SC17599的效力不如吗啡，但在醋酸诱导扭体试验和温水甩尾试验中，它都产生了剂量依赖性的抗伤害感受作用。用阿片拮抗剂纳曲酮和非竞争性μ-阿片受体选择性拮抗剂甲辛酰胺预处理可拮抗SC17599和吗啡的抗伤害感受作用，但δ-阿片受体选择性拮抗剂纳曲吲哚或κ-阿片受体选择性拮抗剂去甲二氢吗啡酮则无此作用。与吗啡类似，给予SC17599也会以剂量依赖性和纳曲酮敏感的方式诱导斯特劳布尾反应。在研究的最高剂量下，与吗啡不同，SC17599不会改变运动活性。甾体SC17599在结构上是一种非常独特的选择性μ-阿片激动剂，其产生的行为效应与吗啡相似，但不完全相同。
