dihydroergotamine (inhaled)

MAP0004 (Levadex) is an investigational drug-device combination product developed for the acute treatment of migraine. It consists of a proprietary formulation of dihydroergotamine (DHE) delivered via the TEMPO inhaler, a breath-synchronized, pressurized metered-dose inhaler (pMDI). The TEMPO technology was designed to provide deep-lung delivery, resulting in rapid systemic absorption and pharmacokinetic profiles similar to intravenous administration while bypassing the gastrointestinal tract and avoiding the 'first-pass' metabolism associated with oral ergotamines. Dihydroergotamine acts as a non-selective agonist at multiple serotonin receptors, primarily 5-HT1B and 5-HT1D, which mediates vasoconstriction of intracranial blood vessels and inhibits the release of pro-inflammatory neuropeptides. Developed by MAP Pharmaceuticals, the program was the primary asset in the company's $958 million acquisition by Allergan in 2013. However, despite successful Phase 3 trials (FREEDOM-301), the product faced significant regulatory hurdles, receiving multiple Complete Response Letters from the FDA primarily due to manufacturing and canister-filling issues. Allergan eventually terminated the program in 2014.

Brand names

Levadex

Other names

TEMPO DHETempo MigraineInhaled Dihydroergotamine