'''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 mg dosages.
'''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 mg dosages.
==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>
'''| [[Methysergide labels and packages|Labels and Packages]]'''
'''| [[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==
==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>
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>
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Methysergide was approved by the [[Food and Drug Administration (United States)|U.S. Food and Drug Administration]] (FDA) in 1962.
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.{{Citation needed|date=August 2013}}
[[Novartis]] withdrew it from the U.S. market after taking over [[Sandoz]], but currently lists it as a product.
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.
↑ 2.02.1Joseph 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. PMID12848667.CS1 maint: Multiple names: authors list (link)
↑Sporer, KA (1995). "The Serotonin Syndrome Implicated Drugs, Pathophysiology and Management". Drug Safety. 13 (2): 94–104. doi:10.2165/00002018-199513020-00004. PMID7576268.CS1 maint: Date and year (link)
↑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. PMID8743744.CS1 maint: Multiple names: authors list (link)
↑Rang, H. P. (2003). Pharmacology. Edinburgh: Churchill Livingstone. ISBN0-443-07145-4. Page 187
↑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. PMID2933009.
↑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. PMID510385.CS1 maint: Multiple names: authors list (link)
↑Bredberg, U. (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. PMID3709634. Unknown parameter |coauthors= ignored (help)
