Currently Enrolling Trials
Migranal (dihydroergotamine mesylate) binds with high affinity to 5-HT1Dα and 5-HT1Dβ receptors.
Migranal is specifically indicated for the acute treatment of migraine headaches with or without aura.
Migranal is supplied as a nasal spray. One spray (0.5 mg) of Migranal (dihydroergotamine mesylate) Nasal Spray should be administered in each nostril. Fifteen minutes later, an additional one spray (0.5 mg) of Migranal (dihydroergotamine mesylate) Nasal Spray should be administered in each nostril, for a total dosage of four sprays (2 mg) of Migranal (dihydroergotamine mesylate) Nasal Spray. Studies have shown no additional benefit from acute doses greater than 2 mg for a single migraine administration.
Mechanism of Action
Dihydroergotamine binds with high affinity to 5-HT1Dα and 5-HT1Dβ receptors. It also binds with high affinity to serotonin 5-HT1A, 5-HT2A, and 5-HT2C receptors, noradrenaline α2A, α2B and α1 receptors, and dopamine D2L and D3 receptors. The therapeutic activity of dihydroergotamine in migraine is generally attributed to the agonist effect at 5-HT1D receptors. Two current theories have been proposed to explain the efficacy of 5-HT1D receptor agonists in migraine. One theory suggests that activation of 5-HT1D receptors located on intracranial blood vessels, including those on arterio-venous anastomoses, leads to vasoconstriction, which correlates with the relief of migraine headache. The alternative hypothesis suggests that activation of 5-HT1D receptors on sensory nerve endings of the trigeminal system results in the inhibition of pro-inflammatory neuropeptide release. In addition, dihydroergotamine possesses oxytocic properties.
Adverse effects associated with the use of Migranal may include, but are not limited to, the following:
- altered sense of taste
- application site reaction
Serious and/or life-threatening peripheral ischemia has been associated with the co-administration of dihydroergotamine with potent CYP 3A4 inhibitors including protease inhibitors and macrolide antibiotics. Because CYP 3A4 inhibition elevates the serum levels of dihydroergotamine, the risk for vasospasm leading to cerebral ischemia and/or ischemia of the extremities is increased. Hence, concomitant use of these medications is contraindicated.
Clinical Trial Results
The efficacy of Migranal (dihydroergotamine mesylate) Nasal Spray for the acute treatment of migraine headaches was evaluated in four randomized, double blind, placebo controlled studies in the U.S. Patients treated a single moderate to severe migraine headache with a single dose of study medication and assessed pain severity over the 24 hours following treatment. Headache response was determined 0.5, 1, 2, 3 and 4 hours after dosing and was defined as a reduction in headache severity to mild or no pain. In studies 1 and 2, a four-point pain intensity scale was utilized; in studies 3 and 4, a five-point scale was used that included both pain response and restoration of function for “severe” or “incapacitating” pain, a less clear endpoint. Although rescue medication was allowed in all four studies, patients were instructed not to use them during the four hour observation period. In studies 3 and 4, a total dose of 2 mg was compared to placebo. In studies 1 and 2, doses of 2 and 3 mg were evaluated, and showed no advantage of the higher dose for a single treatment. In all studies, patients received a regimen consisting of 0.5 mg in each nostril, repeated in 15 minutes (and again in another 15 minutes for the 3 mg dose in studies 1 and 2). The percentage of patients achieving headache response 4 hours after treatment was significantly greater in patients receiving 2 mg doses of Migranal (dihydroergotamine mesylate) Nasal Spray compared to those receiving placebo in 3 of the 4 studies.