Wolff Award presentation 1993. Anti-migraine drug interactions with cloned human 5-hydroxytryptamine1 receptor...

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.