Konno F, Kobayashi C, Morimoto R, Takayanagi I, Cho N, Hirobe M
Arch Int Pharmacodyn Ther. 1986 Aug;282(2):219-32.
We examined the relationship between the pharmacological effects and the interactions of the receptors of nalorphine and its epoxide. The abilities of nalorphine-epoxide to displace [3H]-dihydromorphine (mu-site) and [3H]-ethylketocyclazocine (kappa-site) were practically equal to those of the parent compound, nalorphine, using binding assay to the rat brain membrane preparations. Furthermore, the affinities of mu- and kappa-receptors are virtually uninfluenced by epoxidation of the 7,8-double bond of nalorphine using electrically stimulated mouse and rabbit vasa deferentia. The intrinsic activity of nalorphine, however, is considerably decreased by epoxidation. Moreover, the antagonistic effect of nalorphine to the morphine-induced antinociception (via mu-receptors) was little influenced by epoxidation, but the antinociceptive effect of nalorphine using the acetic acid writhing test was considerably reduced by epoxidation. These results suggest the presence of a higher receptor capacity for the antinociception mediated through kappa-receptors and that the differences between the pharmacological responses of nalorphine and its epoxide are due to the differences of their intrinsic activities.
我们研究了烯丙吗啡及其环氧化物的药理作用与受体相互作用之间的关系。采用大鼠脑膜制剂结合试验，烯丙吗啡环氧化物取代[³H]-二氢吗啡（μ位点）和[³H]-乙基酮环唑辛（κ位点）的能力实际上与母体化合物烯丙吗啡相当。此外，用电刺激小鼠和兔输精管实验发现，烯丙吗啡7,8-双键环氧化后，μ受体和κ受体的亲和力几乎不受影响。然而，烯丙吗啡的内在活性因环氧化作用而显著降低。此外，烯丙吗啡对吗啡诱导的镇痛作用（通过μ受体）的拮抗作用受环氧化影响较小，但在醋酸扭体试验中，烯丙吗啡的镇痛作用因环氧化而显著降低。这些结果表明，κ受体介导的镇痛作用存在较高的受体容量，且烯丙吗啡及其环氧化物药理反应的差异是由于它们内在活性的不同。
