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{{drugbox
{{Drugbox
| IUPAC_name = 1-Methyl-d-lysergic acid-(1-hydroxybut-2-yl)amide
| Watchedfields = changed
| image = Methysergide.gif
| verifiedrevid = 462251649
| width = 178
| 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 chemical structure.png
| width = 150
 
<!--Clinical data-->
| tradename =  Deseril, Sansert
| Drugs.com = {{drugs.com|CONS|methysergide}}
| MedlinePlus = a603022
| pregnancy_AU = C
| pregnancy_US = X
| legal_AU = S4
| legal_CA = Rx-only
| legal_UK = POM
| legal_US = Rx-only
 
<!--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
}}
}}
'''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>.
__NOTOC__
{{CMG}}
 
==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.
 
==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|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>
 
==Pharmacology==
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.|author2=Eyjolfsdottir, G. S. |author3=Paalzow, L. |author4=Tfelt-Hansen, P. |author5=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>
 
==History==
Methysergide was approved by the [[Food and Drug Administration (United States)|U.S. Food and Drug Administration]] (FDA) in 1962.


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.
[[Novartis]] withdrew it from the U.S. market after taking over [[Sandoz]], but currently lists it as a product.{{Citation needed|date=August 2013}}


Like LSD, methysergide also produces [[psychedelic]]
==Synthesis==
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}}
[[File:Methysergide synthesis.png|thumb|center|500px|Methysergide synthesis: [[Sandoz]] Ltd.]]


==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}}

Latest revision as of 18:41, 21 January 2015

Methysergide
Clinical data
Trade namesDeseril, Sansert
AHFS/Drugs.comMicromedex Detailed Consumer Information
MedlinePlusa603022
Pregnancy
category
  • AU: C
  • US: X (Contraindicated)
ATC code
Legal status
Legal status
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)

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

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.

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.[citation needed]

Synthesis

Methysergide synthesis: Sandoz Ltd.

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.; 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

Template:Antimigraine preparations Template:Ergolines

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