Methysergide is a semisynthetic ergot 5-HT₂ receptor antagonist that displays affinity for the 5-HT₁ receptor.⁹   Methysergide (Sansert) is an effective migraine prophylactic in 60% or more of migraineurs and may be especially effective in cluster headache.  The side effects of methysergide include transient muscle aching, claudication, abdominal distress, nausea, weight gain, and hallucination.  The major complication is the rare (1 in 5000) development of retroperitoneal, pulmonary, or endocardial fibrosis.^282,283  It is believed that this major complication may be prevented by having a medication-free interval of four weeks following each six months of continuous treatment.  The dosage should not exceed three of the 2mg pills (6mg total daily dose).

Other agents such as cyproheptadine, pizotifen, and the use of anticonvulsant medications is discussed further elsewhere.^9,237

Another approach to migraine therapy is that of vigorous bilateral compression and massage of the frontal branch of the superficial temporal artery, started at the first sign of visual aura.  The technique was successful in blocking 81% of attacks in 15 patients.²⁸⁴  The authors speculated that the blood vessels of the extra cranial circulation as well as those of the Circle of Willis have perivascular nerve fibers of trigeminal origin.  It may well be that these nerve fibers, rather than the dilation of blood vessels with release of vasoactive substances mediate the pain syndrome of migraine.  Digital massage might stimulate the nerve endings and for some reason stop the ensuing pain phase of the headache.