Feliu A L, Holland M J, Carr K D, Fowler J S, Simon E J
Res Commun Chem Pathol Pharmacol. 1985 Sep;49(3):323-36.
A new fluorinated derivative of N-propylnormetazocine, N-(3-fluoropropyl)-N-normetazocine (1) was synthesized. 1 was similar to the unfluorinated analog 3 in its ability to compete with (3H)-naltrexone for binding sites in rat brain membranes and its potency in antagonizing morphine analgesia in rats. Competition of both compounds against (3H)-naltrexone was little affected by the presence of sodium chloride, a characteristic frequently exhibited by opiate antagonists. Morphine analgesia in rats was measured by suppression of locomotion and vocalization responses to footshock. The ability of 1 to antagonize morphine analgesia in rats was similar to that of 3. Neither 1 nor 3 showed any evidence of agonist activity in rats at doses as high as 1.0 mg/kg (the highest dose tested). These results suggest that 1, labeled with 18F, may be useful for in vivo studies of the opiate receptor using positron emission tomography (PET).
合成了一种新的 N-丙基去甲美沙酮的氟化衍生物，即 N-(3-氟丙基)-N-去甲美沙酮(1)。1 在与(3H)-纳曲酮竞争大鼠脑膜结合位点的能力以及拮抗大鼠吗啡镇痛的效力方面与未氟化类似物 3 相似。两种化合物与(3H)-纳曲酮的竞争受氯化钠存在的影响很小，这是阿片拮抗剂经常表现出的特征。通过抑制对足部电击的运动和发声反应来测量大鼠的吗啡镇痛作用。1 拮抗大鼠吗啡镇痛的能力与 3 相似。在高达 1.0 mg/kg(测试的最高剂量)的剂量下，1 和 3 在大鼠中均未显示出任何激动剂活性的证据。这些结果表明，用 18F 标记的 1 可能有助于使用正电子发射断层扫描(PET)对阿片受体进行体内研究。
