Methysergide

Methysergide

Methysergide
Systematic (IUPAC) name
(6aR,9R)-N-[(2S)-1-Hydroxybutan-2-yl]-4,7-dimethyl-6,6a,8,9-tetrahydroindolo[4,3-fg]quinoline-9-carboxamide
Clinical data
Trade names Deseril, Sansert
AHFS/Drugs.com
MedlinePlus
Pregnancy
category
  • AU: C
  • US: X (Contraindicated)
Legal status
Identifiers
CAS Registry Number  Y
ATC code N02
PubChem CID:
IUPHAR/BPS
DrugBank  Y
ChemSpider  Y
UNII  Y
KEGG  Y
ChEMBL  Y
Chemical data
Formula C21H27N3O2
Molecular mass 353.458 g/mol
 Y   

Methysergide (1-methyl-D-lysergic acid butanolamide or UML-491) is a prescription drug formerly used for prophylaxis of cluster headaches/migraine headaches, but is no longer recommended due to retroperitoneal/retropulmonary fibrosis.

Contents

  • Medical uses 1
  • Side effects 2
  • Pharmacology 3
  • History 4
  • See also 5
  • References 6
  • External links 7

Medical uses

Methysergide is used to treat headaches such as migraine and other recurrent throbbing headaches.[1] Methysergide is one of the most effective[2] medications for the prevention of migraine, but not for the treatment of an acute attack.

It is also used in carcinoid syndrome to treat severe diarrhea.[1] It may also be used in the treatment of serotonin syndrome.[3]

Side effects

It has a known side effect, retroperitoneal fibrosis,[4] which is severe, although uncommon. Other severe but uncommon side effects include pleural fibrosis, and subendocardial fibrosis.

In addition, there is an increased risk of left-sided cardiac valve dysfunction.[2][5]

Pharmacology

Methysergide interacts with serotonin (5-HT) receptors. Its therapeutic effect in migraine prophylaxis has been associated with its antagonism at the 5-HT2B receptor.[6] Furthermore, it is an antagonist at the 5-HT2C receptor, while at the 5-HT1A receptor it serves as a partial agonist.[7][8][9] It is known to have partial agonist effects on some of the other 5-HT receptors as well.[10] Methysergide is metabolised into methylergometrine in humans, which is responsible for its psychedelic effects.[11]

History

Methysergide was approved by the U.S. Food and Drug Administration (FDA) in 1962.

Novartis withdrew it from the U.S. market after taking over Sandoz, but currently lists it as a product.

See also

References

  1. ^ a b http://tranquilene.com/methysergide.html
  2. ^ a b Joseph T, Tam SK, Kamat BR, Mangion JR (2003). "Successful repair of aortic and mitral incompetence induced by methylsergide maleate: confirmation by intraoperative transesophageal echocardiography". Echocardiography 20 (3): 283–7.  
  3. ^ Sporer, KA (1995). "The Serotonin Syndrome Implicated Drugs, Pathophysiology and Management". Drug Safety 13 (2): 94–104.  
  4. ^ emedicine.com (2002)
  5. ^ 1997 Mayo Clinic study linking heart disease to Fen Phen Valvular heart disease associated with fenfluramine-phentermine
  6. ^ Schmuck K, Ullmer C, Kalkman HO, Probst A, Lubbert H (May 1996). "Activation of meningeal 5-HT2B receptors: an early step in the generation of migraine headache?". Eur. J. Neurosci. 8 (5): 959–67.  
  7. ^ Rang, H. P. (2003). Pharmacology. Edinburgh: Churchill Livingstone.   Page 187
  8. ^ Saxena PR, Lawang A (October 1985). "A comparison of cardiovascular and smooth muscle effects of 5-hydroxytryptamine and 5-carboxamidotryptamine, a selective agonist of 5-HT1 receptors". Arch Int Pharmacodyn Ther 277 (2): 235–52.  
  9. ^ http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=9681
  10. ^ Colpaert FC, Niemegeers CJ, Janssen PA (October 1979). "In vivo evidence of partial agonist activity exerted by purported 5-hydroxytryptamine antagonists". Eur. J. Pharmacol. 58 (4): 505–9.  
  11. ^ Bredberg, U.; Eyjolfsdottir, G. S.; Paalzow, L.; Tfelt-Hansen, P.; Tfelt-Hansen, V. (1 January 1986). "Pharmacokinetics of methysergide and its metabolite methylergometrine in man". European Journal of Clinical Pharmacology 30 (1): 75–77.  

External links

  • Novartis Sansert site.
  • Novartis Sansert product description.
  • Migraines.org More detailed information on methysergide.
  • neurologychannel.com, general information on migraines.
  • History of methysergide in migraine.