Migraine - MK-0974

Migraine is a common chronic neurovascular disorder. Current treatments rely on either pain relief, notably with 5-HT1B/1D receptor agonists such as the triptan drugs, or preventive drugs such as β-blockers and antidepressants; even Botox has been used. While these drugs can reduce the frequency, duration and severity of attacks, they can all have side-effects, and they rarely prevent attacks completely.

While the cause of migraine is not fully understood, calcitonin gene related peptide is believed to be implicated as levels in the cranial circulation increase during an attack. Several drugs are under development that block its activity, including Merck & Co's MK-0974, a non-peptide small molecule antagonist at the CRGP receptor.

In a Phase I study, 12 healthy male subjects were given topical doses of capsaicin to increase dermal blood flow after a single oral dose of 300 or 800mg of the drug.¹ Both doses caused a good inhibition of the raised dermal blood flow initiated by capsaicin.

A Phase II study of its effectiveness in relieving the pain caused by migraine has also been carried out.² In the randomised, double blind, placebo- and rizatriptan-controlled dose-ranging trial, oral doses between 25 and 600mg were given to treat moderate to severe migraine attacks. Doses up to 200mg were stopped because of lack of efficacy, and of those given higher doses, two-thirds of 300 and 600mg groups and the rizatriptan group, and half of the 400mg and placebo groups reported pain relief. The drug significantly improved pain relief over placebo after two hours. It was generally well tolerated, and the sustained pain relief after 24 hours was best in the 300mg group. Trials continue.