Pizotifen is a tri-cyclic compound possessing structural similarities to cyproheptadine and tri-cyclic antidepressants. It is given orally for the prophylaxis of migraine and for the prevention of headache attacks during cluster periods. It is not effective in acute attacks of migraine.
The prophylactic effect of Pizotifen is associated with its ability to modify the humoral mechanisms of headache. It inhibits the permeability increasing effect of serotonin and histamine on the affected cranial vessels, thereby checking the transudation of plasmakinin so that the pain threshold of the receptor is maintained at “normal” levels. In the sequence of events leading to migraine attack, depletion of plasma serotonin contributes to loss of tone of extracranial vessels. Pizotifen inhibits serotonin re-uptake by the platelets, thus maintaining plasma serotonin and preventing the loss of tone and passive diffusion of the extracranial arteries.