Nausea, both as a symptom of Migraine and cause by medications, is a significant problem for Migraineurs. Since MAP0004 enters the system via the lungs, it makes sense that it would cause less nausea than medications taken orally or via nasal spray (a portion of which usually gets swallowed). Another potential issue with oral medications is gastric stasis, slowed movement through the stomach and impaired absorption. (See Gastric Stasis Linked To Migraine for more information). In Phase 2 studies with Migraineurs and with asthmatics, treatment with MAP0004 was well-tolerated, with no serious adverse events reported. Drug-induced nausea was very low and Migraine-associated nausea also decreased with treatment.
Over the years, ergotamine medications have had a bad reputation for nausea, constriction of and possible damage to blood vessels, cardiovascular fibrosis, and medication overuse headache (MOH). For the most part, this reputation was deserved. Recent research by Dr. Marcello Bigal indicates that MOH is common with many ergotamine medications, not uncommon with triptans, but not common with DHE. DHE is also now being discovered to prevent the release of CGRP (calcitonin gene receptor peptide), not only at the nerve terminals, but also at the ganglia. CGRP is being investigated as a possible precursor to the activation of neurons that begin a Migraine attack; and another new Migraine abortive being developed by Merck, MK-0974, works by blocking the binding of CGRP to receptors within the central and peripheral nervous system that are important for the transmission of pain impulses and thereby is believed to inhibit the transmission of pain signals that lead to Migraine attacks (See New Migraine Abortive Shows Promise without Vasoconstriction).
Other potentially significant properties of MAP0004 are shortened time to onset of relief and sustained relief. Triptans, DHE-45 injections, and nasal sprays can take up to a hour to onset of relief. In the company's prior Phase 2 efficacy study, MAP0004 provided pain relief in as fast as 10 minutes, with relief sustained through at least 24 hours. The study also demonstrated efficacy trends in treating nausea, photophobia and phonophobia, the other key measurements in treating Migraine.
