Methysergide

Methysergide, sold under the brand names Deseril and Sansert, is a monoaminergic medication of the ergoline and lysergamide groups which is used in the prophylaxis and treatment of migraine and cluster headaches. It has been withdrawn from the market in the United States and Canada due to safety concerns. It is taken by mouth.

The drug is a prodrug of methylergometrine (methylergonovine), which circulates at levels about 10 times higher than those of methysergide during treatment with methysergide. Whereas methysergide is a mixed agonist of some serotonin receptors (e.g., the 5-HT₁ receptors) and antagonist of other serotonin receptors (e.g., the 5-HT₂ receptors), methylergonovine is a non-selective agonist of most of the serotonin receptors, including of both the serotonin 5-HT₁ and 5-HT₂ receptor subgroups. Methysergide and methylergometrine are ergolines and lysergamides and are related to the ergot alkaloids. Previously thought to be an exclusively synthetic compound, it has been reported to occur naturally in Argyreia nervosa (Hawaiian baby woodrose).

Methysergide was first described in the literature by 1958. It is no longer recommended as a first-line therapy for migraines or cluster headaches. This is due to toxicity, such as cardiac valvulopathy, which was first reported with long-term use in the late 1960s. Ergot-based medications like methysergide fell out of favor for treatment of migraine with the introduction of the triptans in the 1980s.