[7-11] While these highly effective medications have improved basic pharmacological PF-2341066 understanding of migraine, enhanced clinical practice,[12] and transformed the lives of many migraine patients,[13] they are associated with a number of important therapeutic limitations, particularly for patients with MRN. For example, not only can oral agents cause nauseated patients to delay

or avoid acute treatment[14, 15] but oral triptans are associated with treatment-emergent nausea in up to 20% of patients.[16] Current treatment guidelines recommend non-oral formulations for nauseated or vomiting patients.[17] With the intranasal formulation of sumatriptan, the challenges are nausea and/or vomiting (13.5%), low bioavailability (∼17%), and a bad or unusual taste reported by 25% of patients who use the 20-mg dose,[18] while high proportions of patients treated with subcutaneous sumatriptan have injection site reactions (59%), and atypical and unpleasant sensations (42%), such RG7204 mw as paresthesias, and pain

and pressure sensations.[19] Taken together, these limitations do as much to explain why dissatisfaction with current medications remains among the most common areas of unmet need for migraineurs[20] as they do to underscore the pressing need for novel approaches to medical treatment for acute migraine. Transdermal delivery represents a non-oral treatment alternative that, until recently, has not been attempted in migraine.[21] Well-established in other disease states, this route of administration has a range of benefits that includes avoidance of the gastrointestinal (GI) tract and first-pass metabolism, sustained and controlled delivery, and convenient usage.[22] Many medications, including nicotine, estrogen, and scopolamine, are delivered through the dermis by passive diffusion, but the barrier properties of the stratum corneum limit passive delivery to low-molecular weight drugs that are lipophilic and effective at low doses.[23] Active transdermal systems, on the other hand, use an external Succinyl-CoA energy source to help propel active drug across the skin, which facilitates

delivery of smaller, lipophilic molecules and allows larger charged and hydrophilic molecules to be transdermally delivered.[21] Among the various active methods of transdermal delivery, iontophoresis – which uses low-level electrical energy to achieve controlled input kinetics and minimum intersubject variability and maintain a steady-state scenario similar to a continuous intravenous infusion[24] – had previously been used to deliver fentanyl, lidocaine, and acyclovir.[23] Initial studies with sumatriptan established that it could be delivered transdermally via iontophoresis technology.[25, 26] Research also confirmed that passive delivery of therapeutic quantities of sumatriptan was not feasible without iontophoresis.