View source for Methysergide

{{Methysergide}}
{{Drugbox
| Watchedfields = changed
| verifiedrevid = 462251649
| IUPAC_name = (6a''R'',9''R'')-''N''-[(2''S'')-1-Hydroxybutan-2-yl]-4,7-dimethyl-6,6a,8,9-tetrahydroindolo[4,3-''fg'']quinoline-9-carboxamide
| image = Methysergide.gif
| width = 150
<!--Clinical data-->
| tradename =
| Drugs.com = {{drugs.com|CONS|methysergide}}
| MedlinePlus = a603022
| pregnancy_category = X
<!--Identifiers-->
| CASNo_Ref = {{cascite|correct|CAS}}
| CAS_number_Ref = {{cascite|correct|??}}
| CAS_number = 361-37-5
| ATC_prefix = N02
| ATC_suffix = CA04
| PubChem = 9681
| IUPHAR_ligand = 134
| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| DrugBank = DB00247
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
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| UNII = XZA9HY6Z98
| KEGG_Ref = {{keggcite|correct|kegg}}
| KEGG = D02357
| ChEMBL_Ref = {{ebicite|correct|EBI}}
| ChEMBL = 1065
<!--Chemical data-->
| C=21 | H=27 | N=3 | O=2
| molecular_weight = 353.458 g/mol
| smiles = O=C(N[C@@H](CC)CO)[C@@H]3/C=C2/c4cccc1c4c(cn1C)C[C@H]2N(C3)C
| InChI = 1/C21H27N3O2/c1-4-15(12-25)22-21(26)14-8-17-16-6-5-7-18-20(16)13(10-23(18)2)9-19(17)24(3)11-14/h5-8,10,14-15,19,25H,4,9,11-12H2,1-3H3,(H,22,26)/t14-,15+,19-/m1/s1
| InChIKey = KPJZHOPZRAFDTN-ZRGWGRIABM
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| StdInChI = 1S/C21H27N3O2/c1-4-15(12-25)22-21(26)14-8-17-16-6-5-7-18-20(16)13(10-23(18)2)9-19(17)24(3)11-14/h5-8,10,14-15,19,25H,4,9,11-12H2,1-3H3,(H,22,26)/t14-,15+,19-/m1/s1
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = KPJZHOPZRAFDTN-ZRGWGRIASA-N
}}__NOTOC__

{{CMG}}

{{SB}} Sansert<sup>®</sup>

==Overview==

'''Methysergide''' ('''1-[[methyl]]-''D''-[[lysergic acid]] [[butanol]][[amide]]''' or '''UML-491''') is a prescription drug formerly used for prophylaxis of [[cluster headaches]]/[[migraine headaches]], but is no longer recommended due to [[retroperitoneal fibrosis|retroperitoneal]]/retropulmonary fibrosis. It was sold under the brand names Sansert and Deseril in 2&nbsp;mg dosages.

==Category==

Antimigraine Drugs

==FDA Package Insert==

'''| [[Methysergide indications and usage|Indications and Usage]]'''
'''| [[Methysergide dosage and administration|Dosage and Administration]]'''
'''| [[Methysergide dosage forms and strengths|Dosage Forms and Strengths]]'''
'''| [[Methysergide contraindications|Contraindications]]'''
'''| [[Methysergide warnings and precautions|Warnings and Precautions]]'''
'''| [[Methysergide adverse reactions|Adverse Reactions]]'''
'''| [[Methysergide drug interactions|Drug Interactions]]'''
'''| [[Methysergide use in specific populations|Use in Specific Populations]]'''
'''| [[Methysergide overdosage|Overdosage]]'''
'''| [[Methysergide description|Description]]'''
'''| [[Methysergide clinical pharmacology|Clinical Pharmacology]]'''
'''| [[Methysergide nonclinical toxicology|Nonclinical Toxicology]]'''
'''| [[Methysergide clinical studies|Clinical Studies]]'''
'''| [[Methysergide how supplied storage and handling|How Supplied/Storage and Handling]]'''
'''| [[Methysergide patient counseling information|Patient Counseling Information]]'''
'''| [[Methysergide labels and packages|Labels and Packages]]'''

==Medical uses==

Methysergide is used to treat headaches such as migraine and other recurrent throbbing headaches.<ref name="patient.co.uk">http://www.patient.co.uk/medicine/Methysergide.htm</ref> Methysergide is one of the most effective<ref name=Tam>{{cite journal |author=Joseph T, Tam SK, Kamat BR, Mangion JR |title=Successful repair of aortic and mitral incompetence induced by methylsergide maleate: confirmation by intraoperative transesophageal echocardiography |journal=Echocardiography |volume=20 |issue=3 |pages=283–7 |year=2003|pmid=12848667 |doi=10.1046/j.1540-8175.2003.03027.x}}</ref> 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]].<ref name="patient.co.uk"/> It may also be used in the treatment of serotonin syndrome.<ref>{{cite journal|last=Sporer|first=KA|title=The Serotonin Syndrome Implicated Drugs, Pathophysiology and Management|journal=Drug Safety|date=1995|year=1995|volume=13|issue=2|pages=94-104|pmid=7576268|doi=10.2165/00002018-199513020-00004}}</ref>

==Side effects==

It has a known [[adverse drug reaction|side effect]], [[retroperitoneal fibrosis]],<ref>[http://www.emedicine.com/radio/topic605.htm emedicine.com (2002)]</ref> 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]].<ref name=Tam/><ref name=mayo>[http://pph.poweradvocates.com/fen_phen_study_mayo.html 1997 Mayo Clinic study linking heart disease to Fen Phen] Valvular heart disease associated with fenfluramine-phentermine</ref>

==Mechanism of Action==

Methysergide interacts with [[5-HT receptor|serotonin (5-HT) receptors]]. Its [[therapeutic effect]] in migraine [[prophylaxis]] has been associated with its antagonism at the [[5-HT2B|5-HT<sub>2B</sub> receptor]].<ref name="pmid8743744">{{cite journal |author=Schmuck K, Ullmer C, Kalkman HO, Probst A, Lubbert H|title=Activation of meningeal 5-HT2B receptors: an early step in the generation of migraine headache?|journal=Eur. J. Neurosci. |volume=8 |issue=5 |pages=959–67 |date=May 1996 |pmid=8743744 |doi= 10.1111/j.1460-9568.1996.tb01583.x|url=}}</ref>

Furthermore, it is an [[receptor antagonist|antagonist]] at the [[5-HT2C|5-HT<sub>2C</sub> receptor]], while at the [[5-HT1A|5-HT<sub>1A</sub> receptor]] it serves as a partial agonist.<ref name=Rang187>{{cite book|author=Rang, H. P. |title=Pharmacology |publisher=Churchill Livingstone |location=Edinburgh |year=2003 |pages=|isbn=0-443-07145-4 |oclc= |doi=}} Page 187</ref><ref name="pmid2933009">{{cite journal |author=Saxena PR, Lawang A |title=A comparison of cardiovascular and smooth muscle effects of 5-hydroxytryptamine and 5-carboxamidotryptamine, a selective agonist of 5-HT1 receptors |journal=Arch Int Pharmacodyn Ther |volume=277|issue=2 |pages=235–52 |date=October 1985 |pmid=2933009 |doi= |url=}}</ref><ref>http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=9681</ref> It is known to have [[partial agonist]]effects on some of the other 5-HT receptors as well.<ref name="pmid510385">{{cite journal |author=Colpaert FC, Niemegeers CJ, Janssen PA |title=In vivo evidence of partial agonist activity exerted by purported 5-hydroxytryptamine antagonists |journal=Eur. J. Pharmacol. |volume=58 |issue=4 |pages=505–9 |date=October 1979 |pmid=510385 |doi= 10.1016/0014-2999(79)90326-1|url=}}</ref> Methysergide is metabolised into[[methylergometrine]] in humans, which is responsible for its psychedelic effects.<ref>{{cite journal|last=Bredberg|first=U.|coauthors=Eyjolfsdottir, G. S., Paalzow, L., Tfelt-Hansen, P., Tfelt-Hansen, V.|title=Pharmacokinetics of methysergide and its metabolite methylergometrine in man|journal=European Journal of Clinical Pharmacology|date=1 January 1986|volume=30|issue=1|pages=75–77|doi=10.1007/BF00614199|pmid=3709634}}</ref>

==Historical Perspective==

Methysergide was approved by the [[Food and Drug Administration (United States)|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==

*[[Triptans]]

==References==

{{Reflist|2}}

==External links==
*[http://www.pharma.us.novartis.com/products/name/sansert.jsp Novartis Sansert site].
*[http://www.pharma.us.novartis.com/product/pi/pdf/Sansert.pdf Novartis Sansert product description].
*[http://www.migraines.org/treatment/tsmthysr.htm Migraines.org More detailed information] on methysergide.
*[http://www.neurologychannel.com/migraine/ neurologychannel.com], general information on migraines.
*[http://www.ncbi.nlm.nih.gov/pubmed/18644039 History of methysergide in migraine.]

{{Antimigraine preparations}}
{{Ergolines}}
{{Hallucinogens}}
{{Serotonergics}}

[[Category:Antimigraine drugs]]
[[Category:Lysergamides]]