Methysergide

From Wikipedia, the free encyclopedia
Jump to: navigation, search
Methysergide
Methysergide chemical structure.svg
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 Micromedex Detailed Consumer Information
MedlinePlus a603022
Pregnancy cat.
Legal status
Identifiers
CAS number 361-37-5 YesY
ATC code N02CA04
PubChem CID 9681
IUPHAR ligand 134
DrugBank DB00247
ChemSpider 9300 YesY
UNII XZA9HY6Z98 YesY
KEGG D02357 YesY
ChEMBL CHEMBL1065 YesY
Chemical data
Formula C21H27N3O2 
Mol. mass 353.458 g/mol
 YesY (what is this?)  (verify)

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.

Medical uses[edit]

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[edit]

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[edit]

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[edit]

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.[citation needed]

Synthesis[edit]

Methysergide synthesis: Sandoz Ltd. GB 811964 

See also[edit]

References[edit]

  1. ^ a b http://www.patient.co.uk/medicine/Methysergide.htm
  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. doi:10.1046/j.1540-8175.2003.03027.x. PMID 12848667. 
  3. ^ Sporer, KA (1995). "The Serotonin Syndrome Implicated Drugs, Pathophysiology and Management". Drug Safety 13 (2): 94–104. doi:10.2165/00002018-199513020-00004. PMID 7576268. 
  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. doi:10.1111/j.1460-9568.1996.tb01583.x. PMID 8743744. 
  7. ^ Rang, H. P. (2003). Pharmacology. Edinburgh: Churchill Livingstone. ISBN 0-443-07145-4.  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. PMID 2933009. 
  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. doi:10.1016/0014-2999(79)90326-1. PMID 510385. 
  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. doi:10.1007/BF00614199. PMID 3709634. 

External links[edit]