New possibilities for anti-migraine drugs: prostanoid antagonists and progesterone-mimicking stabilizers of excitable cells.

Abstract

Medications currently available for the prophylaxis and treatment of migraine provide only limited relief. The pathophysiology of migraine is still poorly understood but it is widely accepted that various 'triggers', including fluctuations in the concentrations of circulating ovarian steroid levels, may initiate alterations in the activity of the intracranial vasculature and its efferent and afferent innervation. Recent pharmacological studies utilizing human intracranial artery preparations have addressed two distinct therapeutic stratagems. First, aspirin-like analgesics, which inhibit prostanoid synthesis, are widely used to treat migraine headache. Recent findings suggest that the ability of mefenamic acid to antagonise certain prostanoid actions, in addition to inhibiting synthesis, enhances its effectiveness. Thus, development of selective antagonists of the intracranial vasoconstrictor and the hyperalgesic actions of prostanoids could provide effective and selective migraine remedies. Second, with regard to prophylaxis, particularly of menstrually-related migraine, drugs which mimic the vascular smooth muscle 'stabilizing' action of ovarian steroids, possibly by enhancing potassium channel activation, are likely to be effective if used at concentrations that have minimal hypotensive effects.