Peroutka S J, Havlik S, Oksenberg D
Department of Neuroscience, Palo Alto Institute of Molecular Medicine, Mountain View, CA 94043.
Headache. 1993 Jul-Aug;33(7):347-50. doi: 10.1111/j.1526-4610.1993.hed3307347.x.
Multiple 5-hydroxytryptamine (5-HT) receptors have been identified in humans. A subgroup of these receptors (designated 5-HT1 receptors) have been hypothesized to be involved in the mechanism of action of acute anti-migraine drugs. At present, this hypothesis cannot be tested directly in human tissues due to technical limitations. However, recent molecular biological advances have allowed for the development of assays employing cloned human 5-HT1 receptors expressed in cells by DNA transfection. This study analyzed the ability of ergotamine, dihydroergotamine, and 5-HT and sumatriptan to interact with the four known human 5-HT1 receptor subtypes. The four acute anti-migraine agents interacted with all 4 human 5-HT1 receptor subtypes with less than 1 microM affinity. However, drug affinities for the human 5-HT1B and 5-HT1D receptors correlate most closely with the rank order of clinical dosages used to treat a migraine attack. Therefore, these data indicate that human 5-HT1B and/or 5-HT1D receptors are likely to mediate the therapeutic efficacy of acute anti-migraine drugs.
在人类中已鉴定出多种5-羟色胺（5-HT）受体。这些受体的一个亚组（称为5-HT1受体）被推测参与急性抗偏头痛药物的作用机制。目前，由于技术限制，该假设无法在人体组织中直接进行测试。然而，最近的分子生物学进展使得能够开发出利用通过DNA转染在细胞中表达的克隆人5-HT1受体的检测方法。本研究分析了麦角胺、双氢麦角胺、5-HT和舒马曲坦与四种已知人类5-HT1受体亚型相互作用的能力。这四种急性抗偏头痛药物与所有4种人类5-HT1受体亚型相互作用，亲和力均小于1微摩尔。然而，药物对人类5-HT1B和5-HT1D受体的亲和力与用于治疗偏头痛发作的临床剂量的排序最为密切相关。因此，这些数据表明人类5-HT1B和/或5-HT1D受体可能介导急性抗偏头痛药物的治疗效果。
