Methysergide: Difference between revisions

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{{drugbox
{{Methysergide}}
| IUPAC_name = 1-Methyl-d-lysergic acid-(1-hydroxybut-2-yl)amide
{{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
| image = Methysergide.gif
| width = 178
 
| 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
| CAS_number = 361-37-5
| ATC_prefix = N02
| ATC_prefix = N02
| ATC_suffix = CA04
| ATC_suffix = CA04
| ATC_supplemental =
| PubChem = 9681
| PubChem = 9681
| DrugBank = APRD00463
| IUPHAR_ligand = 134
| C = 21 | H = 27 | N = 3 | O = 2
| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| DrugBank = DB00247
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 9300
| UNII_Ref = {{fdacite|correct|FDA}}
| 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
| molecular_weight = 353.458 g/mol
| bioavailability =
| smiles = O=C(N[C@@H](CC)CO)[C@@H]3/C=C2/c4cccc1c4c(cn1C)C[C@H]2N(C3)C
| protein_bound =
| 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
| metabolism =
| InChIKey = KPJZHOPZRAFDTN-ZRGWGRIABM
| elimination_half-life =
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| pregnancy_category =
| 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
| legal_status =
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| routes_of_administration =
| StdInChIKey = KPJZHOPZRAFDTN-ZRGWGRIASA-N
}}
}}__NOTOC__
'''Methysergide''' (UML-491) is a prescription drug used for prophylaxis of [[migraine|migraine headaches]] and is sold under the brand names Sansert and Deseril in 2mg dosages. Methysergide was approved by the [[FDA]] in 1962. Its molecular structure is closely related to that of [[LSD]]. It is a 5-HT (serotonin) antagonist. It is a [[receptor antagonist]] for the [[5-HT receptor 2C]]<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>.
'''''For patient information about Methysergide, click [[Methysergide (patient information)|here]]'''''
 
{{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.
 
==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 is one of the most effective medications for the prevention of migraine, but not for the treatment of an acute attack. 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. [[Novartis]] withdrew it from the U.S. market after taking over [[Sandoz]], but currently lists it as a product.
==Category==


Like LSD, methysergide also produces [[psychedelic]]
Antimigraine Drugs
and [[Psychedelics, dissociatives and deliriants|hallucinogenic]] effects above a dosage of about 4mg.<ref>L. Bender (1970): "Children's Reactions to Psychotomimetic Drugs", Psychotomimetic Drugs, pp. 265-273]</ref> Full effects are felt with dosages of 8-20mg.{{Fact|date=February 2007}}
 
==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]]'''
 
==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.{{Citation needed|date=August 2013}}


==See also==
==See also==
[[Triptan]]
*[[Triptans]]


==References==
==References==
<references/>
{{Reflist|2}}


==External links==
==External links==
*[http://www.pharma.us.novartis.com/products/name/sansert.jsp Novartis Sansert site].  
*[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.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.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.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}}
{{Ergolines}}
{{Antimigraine preparations}}
{{Hallucinogens}}
{{Serotonergics}}
 
[[Category:Antimigraine drugs]]
[[Category:Antimigraine drugs]]
[[Category:Lysergamides]]
[[Category:Lysergamides]]
[[ja:メチセルジド]]
{{WikiDoc Sources}}

Revision as of 19:07, 7 February 2014

Methysergide
SANSERT® FDA Package Insert
Indications and Usage
Dosage and Administration
Contraindications
Warnings and Precautions
Adverse Reactions
Drug Interactions
Use in Specific Populations
Overdosage
Description
Clinical Pharmacology
Nonclinical Toxicology
How Supplied/Storage and Handling
Patient Counseling Information
Clinical Trials on Methysergide
ClinicalTrials.gov
Methysergide
Clinical data
AHFS/Drugs.comMicromedex Detailed Consumer Information
MedlinePlusa603022
Pregnancy
category
  • X
ATC code
Identifiers
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEMBL
E number{{#property:P628}}
ECHA InfoCard{{#property:P2566}}Lua error in Module:EditAtWikidata at line 36: attempt to index field 'wikibase' (a nil value).
Chemical and physical data
FormulaC21H27N3O2
Molar mass353.458 g/mol
3D model (JSmol)
  (verify)

For patient information about Methysergide, click here

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Synonyms / Brand Names: Sansert®

Overview

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. 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.[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]

Category

Antimigraine Drugs

FDA Package Insert

| Indications and Usage | Dosage and Administration | Dosage Forms and Strengths | Contraindications | Warnings and Precautions | Adverse Reactions | Drug Interactions | Use in Specific Populations | Overdosage | Description | Clinical Pharmacology | Nonclinical Toxicology | Clinical Studies | How Supplied/Storage and Handling | Patient Counseling Information | Labels and Packages

Mechanism of Action

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 agonisteffects on some of the other 5-HT receptors as well.[10] Methysergide is metabolised intomethylergometrine in humans, which is responsible for its psychedelic effects.[11]

Historical Perspective

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]

See also

References

  1. ↑ 1.0 1.1 http://www.patient.co.uk/medicine/Methysergide.htm
  2. ↑ 2.0 2.1 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. (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. Unknown parameter |coauthors= ignored (help)

External links

Template:Antimigraine preparations Template:Ergolines

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