Anti-Migraine Drug Interactions with Cloned Human 5-Hydroxytryptamine 1 , Receptor Subtypes

Abstract

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.

Binding Properties of Dipropyltryptamine at the Human 5-HT1a Receptor

“…(known to contain DMT) in the successful treatment of migraine headaches [14,15] . DMT is known to display agonistic activity at 5-HT1aRs, and antagonistic activity at 5-HT2aRs [11] , precisely the same qualities suggested as pertinent to acute symptomatic and prophylactic treatment of migraine, respectively [14,[16][17][18] .…”

Dihydroergotamine, Ergotamine, Methysergide and Sumatriptan – Basic Science in Relation to Migraine Treatment

“…All the receptors, with the exception of the 5‐HT 3 receptor, belong to the super family of 7 transmembrane domain G‐protein‐linked receptors 3 . The 5‐HT receptor family mediates the effects of several drugs highly effective in migraine primarily by activating 5‐HT 1B , 5‐HT 1D , and 5‐HT 1F receptors 4‐7 . The ergot alkaloids, also referred to as “ergots,” ergotamine, dihydroergotamine (DHE), and methysergide, as well as the “triptan” sumatriptan, are all agonists for these receptors 8,9 .…”