Product Code Database
Methysergide, sold under the brand names Deseril and Sansert, is a monoaminergic medication which is used in the prophylaxis and treatment of migraine and . It has been withdrawn drug in the United States and Canada due to drug safety concerns. The drug has also been found to produce psychedelic drug effects at high doses. It is taken orally.
The drug is a prodrug of methylergometrine (methylergonovine), which circulates at levels about 10times higher than those of methysergide. Whereas methysergide is a mixed agonist of some serotonin receptors (e.g., the serotonin 5-HT1 receptors) and antagonist of other serotonin receptors (e.g., the serotonin 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 . (2025). 9783642074813, Springer Berlin Heidelberg. ISBN 9783642074813
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 in the 1980s.
Methysergide has been known as an effective treatment for migraine and cluster headache for over 50 years. A 2016 investigation by the European Medicines Agency due to long-held questions about safety concerns was performed. To assess the need for continuing availability of methysergide, the International Headache Society performed an electronic survey among their professional members.
The survey revealed that 71.3% of all respondents had ever prescribed methysergide and 79.8% would prescribe it if it were to become available. Respondents used it more in cluster headache than migraine, and reserved it for use in refractory patients.
The European Medicines Agency (EMA) concluded "that the vast majority of headache experts in this survey regarded methysergide a unique treatment option for specific populations for which there are no alternatives, with an urgent need to continue its availability." This position was supported by the International Headache Society.
Updated guidelines published by Britain's National Health Service Migraine Trust in 2014 recommended "Methysergide medicines are now only to be used for preventing severe intractable migraine and cluster headache when standard medicines have failed".
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! Site
! Affinity (Ki, nM) ! Efficacy (Emax, %) ! Action | |||
| 5-HT1A | 14–25 | 89% | Agonist |
| 5-HT1B | 2.5–162 | ? | Full agonist |
| 5-HT1D | 3.6–93 | 50 | Partial agonist |
| 5-HT1E | 59–324 | ? | Full agonist |
| 5-HT1F | 34 | ? | Full agonist |
| 5-HT2A | 1.6–104 | 0 | ? |
| 5-HT2B | 0.1–150 | 0–20 | Antagonist |
| 5-HT2C | 0.95–4.5 | 0 | Antagonist |
| 5-HT3 | >10,000 | – | – |
| 5-HT5A | >10,000 | – | Antagonist |
| 5-HT5B | 41–1,000 | ? | ? |
| 5-HT6 | 30–372 | ? | ? |
| 5-HT7 | 30–83 | ? | Antagonist |
| α1A | >10,000 | – | – |
| α1B | >10,000 | – | – |
| α1D | ? | ? | ? |
| α2A | 170–>1,000 | ? | ? |
| α2B | 106 | ? | ? |
| α2C | 88 | ? | ? |
| β1 | >10,000 | – | – |
| β2 | >10,000 | – | – |
| D1 | 290 | ? | ? |
| D2 | 200–>10,000 | ? | ? |
| D3 | >10,000 | – | – |
| D4 | >10,000 | – | – |
| D5 | >10,000 | – | – |
| H1 | 3,000–>10,000 | ? | ? |
| H2 | >10,000 | – | – |
| M1 | 5,459 | ? | ? |
| M2 | 6,126 | ? | ? |
| M3 | 4,632 | ? | ? |
| M4 | >10,000 | – | – |
| M5 | >10,000 | – | – |
| Notes: All sites are human except 5-HT5B (mouse/rat—no human counterpart) and D3 (rat). Negligible affinity (>10,000 nM) for various other receptors (GABA receptor, glutamate, nicotinic acetylcholine, prostanoid) and for the monoamine transporters (SERT, NET, DAT). Methysergide's major active metabolite, methylergonovine, also contributes to its activity, most notably 5-HT2A and 5-HT2B receptor partial agonism. Refs: Additional refs: | |||
Methysergide interacts with the serotonin 5-HT1A, 5-HT1B, 5-HT1D, 5-HT1E, 5-HT1F, 5-HT2A, 5-HT2B, 5-HT2C, 5-HT5A, 5-HT6, and 5-HT7 receptors and the α2A-, α2B-, and α2C-adrenergic receptors. It does not have significant affinity for human 5-HT3, dopamine, α1-adrenergic, β-adrenergic, acetylcholine, GABA receptor, glutamate, cannabinoid, or histamine receptors, nor for the monoamine transporters. Methysergide is an agonist of 5-HT1 receptors, including a partial agonist at the 5-HT1A receptor, and is an antagonist at the 5-HT2A, 5-HT2B, 5-HT2C, and 5-HT7 receptors. (2025). 9780443071454, Churchill Livingstone. ISBN 9780443071454 Page 187 Methysergide is drug metabolism into methylergometrine in humans, which in contrast to methysergide is a partial agonist of the 5-HT2A and 5-HT2B receptors and also interacts with various other targets.
Methysergide antagonizes the effects of serotonin in blood vessels and gastrointestinal smooth muscle, but has few of the properties of other ergot alkaloids. It is thought that metabolism of methysergide into its active metabolite methylergonovine is responsible for the antimigraine effects of methysergide. (2025). 9789811059773 ISBN 9789811059773 Methylergonovine appears to be 10times more potent than methysergide as an agonist of the 5-HT1B and 5-HT1D receptors and has higher intrinsic efficacy in activating these receptors. The antimigraine activity of methysergide might be specifically due to serotonin 5-HT2B receptor antagonism.
Drug metabolism of methysergide into methylergonovine, which is a potent serotonin 5-HT2A receptor agonist, is considered to be responsible for the psychedelic drug effects of methysergide at high doses. The psychedelic effects can specifically be attributed to activation of the serotonin 5-HT2A receptor. (2025). 9780444641250 ISBN 9780444641250 The drug can activate the serotonin 5-HT2B receptor due to metabolism into methylergonovine and for this reason has been associated with cardiac valvulopathy. It is thought that the serotonin receptor antagonism of methysergide is not able to overcome the serotonin receptor agonism of methylergonovine due to the much higher levels of methylergonovine during methysergide therapy.
Methysergide was synthesized from lysergic acid by adding a methyl group and a butanolamid group. This resulted in a compound with selectivity and high potency as a serotonin (5-HT) inhibitor. Based on the possible involvement of serotonin in migraine attacks, it was introduced in 1959 by Sicuteri as a preventive drug for migraine. The clinical effect was often excellent, but 5 years later it was found to cause retroperitoneal fibrosis after chronic intake.
Consequently, the use of the drug in migraine declined considerably, but it was still used as a 5-HT antagonist in experimental studies. In 1974 Saxena showed that methysergide had a selective vasoconstrictor effect in the carotid bed and in 1984 he found an atypical receptor. This finding provided an incentive for the development of sumatriptan.
Novartis withdrew it from the U.S. market after taking over Sandoz, but currently lists it as a discontinued product. United States production of methysergide (Sansert) was discontinued on the manufacturer's own behalf in 2002. Sansert had previously been produced by Sandoz, which merged with Ciba-Geigy in 1996, and led to the creation of Novartis. In 2003 Novartis united its global generics businesses under a single global brand, with the Sandoz name and product line reviewed and reestablished.
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