Pharmacological opportunities and pitfalls in the therapy of migraine.

The mild vasoconstrictor effects of modern antimigraine drugs, such as serotonin (5-HT; 5-hydroxytryptamine)1B/D agonists, have led to a search for nonvasoconstrictor approaches to therapy. Such approaches have included substance P (neurokinin I) antagonists, endothelin antagonists and highly specific 5HT1D agonists. All of these substances are effective in animal models and have no significant vasoconstrictive effects. However, all of them failed to demonstrate any antimigraine effects. Current clinical and experimental evidence therefore supports the view that isolated peripheral trigeminal nerve inhibition is insufficient to relieve acute migraine.