Peroutka S J, McCarthy B G, Guan X M
Department of Neurology, Stanford University School of Medicine, CA 94305.
Life Sci. 1991;49(6):409-18. doi: 10.1016/0024-3205(91)90582-v.
The ability of nineteen tryptamine derivatives to interact with putative 5-hydroxytryptamine1D (5-HT1D) receptor binding sites in bovine caudate was analyzed. Sixteen of the nineteen agents competed, with variable potency, for these binding sites with Hill slopes of approximately unity. By contrast, 5-carboxyamidotryptamine (5-CT), sumatriptan and 5-benzyloxytryptamine (5-BT) competed with Hill slope values significantly less than unity. These three drugs share, in comparison to the sixteen other tryptamines, relatively large substitutions at the 5-position of the indole moiety. Additional radioligand binding studies with 5-BT indicate that the drug shows relative selectivity for 5-HT1D/1B binding sites. Functionally, 5-BT and sumatriptan inhibit 3H-5-HT release from guinea pig cortical synaptosomes with equal potency but 5-BT is significantly less efficacious than sumatriptan. These data indicate that 5-BT is a relatively selective partial agonist at 5-HT1D receptors.
分析了19种色胺衍生物与牛尾状核中假定的5-羟色胺1D（5-HT1D）受体结合位点相互作用的能力。19种试剂中的16种以不同的效力与这些结合位点竞争，希尔斜率约为1。相比之下，5-羧酰胺色胺（5-CT）、舒马曲坦和5-苄氧基色胺（5-BT）的竞争希尔斜率值明显小于1。与其他16种色胺相比，这三种药物在吲哚部分的5位具有相对较大的取代基。用5-BT进行的额外放射性配体结合研究表明，该药物对5-HT1D/1B结合位点具有相对选择性。在功能上，5-BT和舒马曲坦以相同的效力抑制豚鼠皮质突触体中3H-5-HT的释放，但5-BT的效力明显低于舒马曲坦。这些数据表明，5-BT是5-HT1D受体相对选择性的部分激动剂。
