Methysergide

Methysergide
Clinical data
Trade names	Deseril, Sansert
AHFS/Drugs.com	Micromedex Detailed Consumer Information
MedlinePlus	a603022
Pregnancy; category	AU: C ; US: X (Contraindicated) ; ;
ATC code	N02CA04 (WHO) ;
Legal status
Legal status	AU: S4 (Prescription only) ; CA: ℞-only ; UK: POM (Prescription only) ; US: ℞-only ;
Identifiers
	IUPAC name (6aR,9R)-N-[(2S)-1-Hydroxybutan-2-yl]-4,7-dimethyl-6,6a,8,9-tetrahydroindolo[4,3-fg]quinoline-9-carboxamide;
CAS Number	361-37-5 ;
PubChem CID	9681;
IUPHAR/BPS	134;
DrugBank	DB00247 ;
ChemSpider	9300 ;
UNII	XZA9HY6Z98;
KEGG	D02357 ;
ChEMBL	ChEMBL1065 ;
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
Formula	C21H27N3O2
Molar mass	353.458 g/mol
3D model (JSmol)	Interactive image;
	SMILES O=C(N[C@@H](CC)CO)[C@@H]3/C=C2/c4cccc1c4c(cn1C)C[C@H]2N(C3)C;
	InChI InChI=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 ; Key:KPJZHOPZRAFDTN-ZRGWGRIASA-N ;
(verify)

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

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/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-HT_2B receptor.^[6] Furthermore, it is an antagonist at the 5-HT_2C receptor, while at the 5-HT_1A 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

References

↑ ^1.0 ^1.1 http://www.patient.co.uk/medicine/Methysergide.htm
↑ ^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.
↑ 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.
↑ emedicine.com (2002)
↑ 1997 Mayo Clinic study linking heart disease to Fen Phen Valvular heart disease associated with fenfluramine-phentermine
↑ 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.
↑ Rang, H. P. (2003). Pharmacology. Edinburgh: Churchill Livingstone. ISBN 0-443-07145-4. 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. PMID 2933009.
↑ http://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=9681
↑ 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.
↑ 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

Novartis Sansert site.
Novartis Sansert product description.
Migraines.org More detailed information on methysergide.
neurologychannel.com, general information on migraines.
History of methysergide in migraine.

Template:Antimigraine preparations Template:Ergolines

[patient.co.uk-1] 1.0 ^1.1 http://www.patient.co.uk/medicine/Methysergide.htm

[Tam-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] .com (2002)

[mayo-5] 1997 Mayo Clinic study linking heart disease to Fen Phen Valvular heart disease associated with fenfluramine-phentermine

[pmid8743744-6] 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.

[Rang187-7] Rang, H. P. (2003). Pharmacology. Edinburgh: Churchill Livingstone. ISBN 0-443-07145-4. Page 187

[pmid2933009-8] 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] ttp://pubchem.ncbi.nlm.nih.gov/summary/summary.cgi?cid=9681

[pmid510385-10] 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.

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