Roerig S C, Arteau C, Fujimoto J M
Department of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee.
Proc Soc Exp Biol Med. 1987 Nov;186(2):234-9. doi: 10.3181/00379727-186-42609.
Nalmefene is an orally active opiate antagonist structurally related to naloxone and naltrexone. In this study using two different strains of mice (Swiss Cox and ICR), the antagonist activity of nalmefene given subcutaneously (sc) was quantified by determination of the apparent pA2 values against the antinociceptive activity (tail flick and hot plate tests) of morphine given sc or intrathecally (lumbar spinal cord). The apparent pA2 values (constrained to a slope of -1) were 8.06 (7.79-8.33) in Swiss Cox mice and 7.81 (7.62-8.00) in ICR mice in the tail flick test with sc morphine. These values were larger than the corresponding value for naloxone in ICR mice, 7.35 (7.10-7.60). The hot plate test provided similar results: the apparent pA2 values for nalmefene with sc morphine were 8.14 (7.89-8.39) in Swiss Cox mice and 7.81 (7.65-7.97) in ICR mice, values which were different from naloxone 7.33 (7.23-7.42) in ICR mice. Apparent pA2 values for nalmefene with intrathecal morphine were not different from those for naloxone in the tail flick test. Thus, these sets of results suggest that it may be worthwhile to further determine whether systemic nalmefene might possibly possess an advantage over naloxone in antagonizing systemic side effects of morphine arising from local spinal morphine administration.
纳美芬是一种口服活性阿片类拮抗剂，在结构上与纳洛酮和纳曲酮相关。在这项使用两种不同品系小鼠（瑞士考克斯小鼠和ICR小鼠）的研究中，通过测定皮下注射纳美芬对皮下或鞘内（腰段脊髓）注射吗啡的抗伤害感受活性（甩尾试验和热板试验）的表观pA2值，对皮下注射纳美芬的拮抗活性进行了定量。在甩尾试验中，对于皮下注射吗啡的瑞士考克斯小鼠，表观pA2值（斜率限定为-1）为8.06（7.79 - 8.33），ICR小鼠为7.81（7.62 - 8.00）。这些值大于ICR小鼠中纳洛酮的相应值7.35（7.10 - 7.60）。热板试验提供了类似的结果：对于皮下注射吗啡的纳美芬，瑞士考克斯小鼠的表观pA2值为8.14（7.89 - 8.39），ICR小鼠为7.81（7.65 - 7.97），这些值与ICR小鼠中纳洛酮的7.33（7.23 - 7.42）不同。在甩尾试验中，鞘内注射吗啡时纳美芬的表观pA2值与纳洛酮的没有差异。因此，这些结果表明，进一步确定全身性纳美芬在拮抗局部脊髓注射吗啡引起的吗啡全身性副作用方面是否可能比纳洛酮具有优势可能是值得的。
