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Anti‐Migraine Drug Interactions with Cloned Human 5‐Hydroxytryptamine 1 , Receptor Subtypes
Author(s) -
Peroutka Stephen J.,
Havlik Sona,
Oksenberg Donna
Publication year - 1993
Publication title -
headache: the journal of head and face pain
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.14
H-Index - 119
eISSN - 1526-4610
pISSN - 0017-8748
DOI - 10.1111/j.1526-4610.1993.hed3307347.x
Subject(s) - ergotamine , dihydroergotamine , receptor , sumatriptan , migraine , pharmacology , 5 ht receptor , 5 ht1 receptor , biology , drug , mechanism of action , serotonin , medicine , agonist , in vitro , biochemistry
SYNOPSIS Multiple 5‐hydroxytryptamine (5‐HT) receptors have been identified in humans. A subgroup of these receptors (designated 5‐HT 1 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‐HT 1 receptors expressed in cells by DNA transfection. This study analyzed the ability of ergotamine, dihydroergotamine, 5‐HT and sumatriptan to interact with the four known human 5‐HT 1 receptor subtypes. The four acute anti‐migraine agents interacted with all 4 human 5‐HT 1 receptor subtypes with less than 1 μM affinity. However, drug affinities for the human 5‐HT 1B and 5‐HT 1D receptors correlate most closely with the rank order of clinical dosages used to treat a migraine attack. Therefore, these data indicate that human 5‐HT 1B and/or 5‐HT 1D receptors are likely to mediate the therapeutic efficacy of acute anti‐migraine drugs.