Deliganis A V, Peroutka S J
Department of Neurology, Stanford University Medical Center, CA 94305-5235.
Headache. 1991 Apr;31(4):228-31. doi: 10.1111/j.1526-4610.1991.hed3104228.x.
The interactions of four abortive anti-migraine agents and four prophylactic anti-migraine agents with 5-HT1D receptors in bovine brain were analyzed using radioligand binding techniques and adenylate cyclase assays. In bovine caudate, the affinities of abortive anti-migraine agents (i.e. 5-hydroxytryptamine, ergotamine, dihydroergotamine, sumatriptan) for 5-HT1D receptors range from 4.0-34 nM while the affinities of prophylactic anti-migraine agents (i.e. methysergide, amitriptyline, (-)propranolol, verapamil) range from 46-11,000 nM. In adenylate cyclase studies in bovine substantia nigra, all four abortive anti-migraine agents dose-dependently inhibit forskolin-stimulated adenylate cyclase activity, a biochemical effect mediated by 5-HT1D receptors. No agonist effect on cyclase activity is observed with the four prophylactic anti-migraine agents. These data support the hypothesis that abortive anti-migraine agents are 5-HT1D receptor agonists and that this effect may underlie their anti-migraine efficacy.
运用放射性配体结合技术和腺苷酸环化酶分析方法，对四种终止性抗偏头痛药物和四种预防性抗偏头痛药物与牛脑5-HT1D受体的相互作用进行了分析。在牛尾状核中，终止性抗偏头痛药物（即5-羟色胺、麦角胺、双氢麦角胺、舒马曲坦）对5-HT1D受体的亲和力范围为4.0 - 34 nM，而预防性抗偏头痛药物（即甲基麦角新碱、阿米替林、（-）普萘洛尔、维拉帕米）的亲和力范围为46 - 11,000 nM。在牛黑质的腺苷酸环化酶研究中，所有四种终止性抗偏头痛药物均呈剂量依赖性抑制福司可林刺激的腺苷酸环化酶活性，这是一种由5-HT1D受体介导的生化效应。四种预防性抗偏头痛药物未观察到对环化酶活性的激动作用。这些数据支持了以下假说：终止性抗偏头痛药物是5-HT1D受体激动剂，且这种效应可能是其抗偏头痛疗效的基础。
