Methysergide: Difference between revisions

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{{DrugProjectFormSinglePage
|authorTag={{SG}}
|genericName=Methysergide maleate
|aOrAn=an
|drugClass=antimigraine
|indicationType=prophylaxis
|indication= vascular headaches
|hasBlackBoxWarning=Yes
|blackBoxWarningTitle=<b><span style="color:#FF0000;">WARNING</span></b>
|blackBoxWarningBody=<i><span style="color:#FF0000;"></span></i> Retroperitoneal Fibrosis, Pleuropulmonary Fibrosis and Fibrotic Thickening of Cardiac Valves May Occur in Patients Receiving Long-term Methysergide Maleate Therapy. Therefore, This Preparation Must Be Reserved for Prophylaxis in Patients Whose Vascular Headaches Are Frequent and/or Severe and Uncontrollable and Who Are Under Close Medical Supervision.
|fdaLIADAdult=*4-8 mg daily.
*Tablets to be given with meals.
*There must be a medication-free interval of 3-4 weeks after every 6-month course of treatment.
|offLabelAdultGuideSupport=There is limited information regarding <i>Off-Label Guideline-Supported Use</i> of Methysergide in adult patients.
|offLabelAdultNoGuideSupport=There is limited information regarding <i>Off-Label Non–Guideline-Supported Use</i> of Methysergide in adult patients.
|offLabelPedGuideSupport=There is limited information regarding <i>Off-Label Guideline-Supported Use</i> of Methysergide in pediatric patients.
|offLabelPedNoGuideSupport=There is limited information regarding <i>Off-Label Non–Guideline-Supported Use</i> of Methysergide in pediatric patients.
|contraindications=Hypersensitivity to the drug or to tartrazine (FD&C Yellow #5) or any other components of the formulation, pregnancy, lactation, peripheral vascular disease, severe arteriosclerosis, severe hypertension, coronary artery disease, phlebitis or cellulitis of the lower limbs, pulmonary disease, collagen diseases or fibrotic processes, impaired liver or renal function, valvular heart disease, debilitated states and serious infections.
|warnings=With long-term, uninterrupted administration, retroperitoneal fibrosis or related conditions — pleuropulmonary fibrosis and cardiovascular disorders with murmurs or vascular bruits have been reported. Patients must be warned to report immediately the following symptoms and to discontinue the drug: cold, numb, and painful hands and feet; leg cramps on walking; any type of girdle, flank, or chest pain, shortness of breath, or any associated symptomatology. Should any of these symptoms develop, methysergide should be discontinued. Continuous administration should not exceed 6 months. There must be a drug-free interval of 3-4 weeks after each 6-month course of treatment. The dosage should be reduced gradually during the last 2-3 weeks of each treatment course to avoid “headache rebound.”
The drug is not recommended for use in children.
|clinicalTrials=ithin the recommended dose levels, the following side effects have been reported:
1)      Fibrotic Complications
Fibrotic changes have been observed in the retroperitoneal, pleuropulmonary, cardiac, and other tissues, either singly or, very rarely, in combination.
Retroperitoneal Fibrosis
This nonspecific fibrotic process is usually confined to the retroperitoneal connective tissue above the pelvic brim and may present clinically with one or more symptoms such as general malaise, fatigue, weight loss, backache, low grade fever (elevated sedimentation rate), urinary obstruction (girdle or flank pain, dysuria, polyuria, oliguria, elevated BUN), vascular insufficiency of the lower limbs (leg pain, Leriche syndrome, edema of legs, thrombophlebitis). The single most useful diagnostic procedure in suspected cases of retroperitoneal fibrosis is intravenous pyelography. Typical deviation and obstruction of one or both ureters may be observed.
Pleuropulmonary Complications
A similar nonspecific fibrotic process, limited to the pleural and immediately subjacent pulmonary tissues, usually presents clinically with dyspnea, tightness and pain in the chest, pleural friction rubs, and pleural effusion. These findings may be confirmed by chest X-ray.
Cardiac Complications
Nonrheumatic fibrotic thickenings of the aortic root and of the aortic and mitral valves usually present clinically with cardiac murmurs and dyspnea.
Other Fibrotic Complications
Several cases of fibrotic plaques, simulating Peyronie’s Disease have been described.
2)      Cardiovascular Complications
Encroachment of retroperitoneal fibrosis on the aorta, inferior vena cava and their common iliac branches may result in vascular insufficiency of the lower limbs, the presenting features of which are mentioned under Retroperitoneal Fibrosis.
Intrinsic vasoconstriction of large and small arteries, involving one or more vessels or merely a segment of a vessel, may occur at any stage of therapy. Depending on the vessel involved, this complication may present with chest pain, abdominal pain, or cold, numb, painful extremities with or without paresthesias and diminished or absent pulses. Progression to ischemic tissue damage has rarely been reported. Prompt withdrawal of the drug at the first signs of impaired circulation is recommended (see WARNINGS) to obviate such effects.
Postural hypotension and tachycardia have also been observed.
3)      Gastrointestinal Symptoms
Nausea, vomiting, diarrhea, heartburn, abdominal pain. These effects tend to appear early and can frequently be obviated by gradual introduction of the medication and by administration of the drug with meals. Constipation and elevation of gastric HCl have also been reported.
4)      CNS Symptoms
Seizure, insomnia, drowsiness, mild euphoria, dizziness, ataxia, lightheadedness, hyperesthesia, unworldly feelings (described variously as “dissociation”, “hallucinatory experiences”, etc.). Some of these symptoms may be associated with vascular headaches, per se, and may, therefore, be unrelated to the drug.
5)      Dermatological Manifestations
Facial flush, telangiectasia, and nonspecific rashes have rarely been reported. Increased hair loss may occur, but in many instances the tendency has abated despite continued therapy.
6)      Edema
Peripheral edema, and, more rarely, localized brawny edema may occur.
Dependent edema has responded to lowered doses, salt restriction, or diuretics.
7)      Weight Gain
Weight gain may be a reason to caution patients regarding their caloric intake.
8)      Hematological Manifestations
Neutropenia, eosinophilia, and thrombocytopenia.
9)      Miscellaneous
Weakness, arthralgia, myalgia, fever, and mydriasis.
|administration=====Methysergide maleate tablets, USP====
*Tablets 2 mg
*Bright yellow, coated tablets with “SANDOZ” imprinted on one side, “78-58” imprinted on the other side, in black.
*Bottle of 100……………………………………………….……………..NDC 0078-0058-05
|overdose=Few cases of acute Sansert® (methysergide maleate) intoxication have been reported. The possible symptom complex is therefore not fully known. The following symptoms are based on these few case reports. Euphoria, hyperactivity, tachycardia, dilated pupils, and dizziness have been reported in a child with a dose of 20-24 mg of Sansert® (methysergide maleate). In adults, peripheral vasospasm, with diminished or absent pulses, coldness, mottling and cyanosis, has been observed at a dose of 200 mg. Ischemic tissue damage has not been reported in acute overdosage with Sansert® (methysergide maleate).
Treatment consists of removal of the offending drug by induction of emesis, or gastric lavage in the case of very recent intake, repeat dose administration of activated charcoal and catharsis. There is no evidence that forced diuresis accelerates the elimination of Sansert® (methysergide maleate). However, I.V. fluids may be given as a general supportive measure.
Treatment of peripheral vasospasm should consist of warmth, but not heat, and protection of the ischemic limbs. In reported cases of Sansert® (methysergide maleate) overdosage, the use of vasodilators has not been necessary. However, if vasospasm is persistent, severe, or if there is evidence of impending ischemic tissue damage, these agents may be beneficial. Careful nursing care is recommended in order to prevent tissue damage.
Up-to-date information about the treatment of overdose can often be obtained from a certified Regional Poison Control Center. Telephone numbers of certified Regional Poison Control Centers are listed in the Physicians’ Desk Reference®.*
|mechAction=methysergide maleate) has been shown, in vitro and in vivo, to inhibit or block the effects of serotonin, a substance which may be involved in the mechanism of vascular headaches. Serotonin has been variously described as a central neurohumoral agent or chemical mediator, as a “headache substance” acting directly or indirectly to lower pain threshold (others in this category include tyramine; polypeptides, such as bradykinin; histamine; and acetylcholine), as an intrinsic “motor hormone” of the gastrointestinal tract, and as a “hormone” involved in connective tissue reparative processes. Suggestions have been made by investigators as to the mechanism whereby methysergide produces its clinical effects, but this has not been finally established.
|structure=is a partially synthetic compound structurally related to lysergic acid butanolamide, well-known as methylergonovine in obstetrical practice as an oxytocic agent.
Chemically, methysergide maleate is designated as ergoline-8-carboxamide, 9,10-didehydro-N-[1-(hydroxymethyl)propyl]-1,6-dimethyl-, (8ß)-, (Z)-2-butenedioate (1:1) (salt).
Its structural formula is:
[[File:Methysergide maleate chemical structure (2).png|none|450px]]
Methylation in the number 1 position of the ring structure enormously enhances the antagonism to serotonin which is present to a much lesser degree in the partially methylated compound (methylergonovine maleate) as well as profoundly altering other pharmacologic properties.
|howSupplied=====Methysergide maleate tablets, USP====
*Tablets 2 mg
*Bright yellow, coated tablets with “SANDOZ” imprinted on one side, “78-58” imprinted on the other side, in black.
*Bottle of 100……………………………………………….……………..NDC 0078-0058-05
|storage=*Below 86°F (30°C); tight container.
|packLabel=[[File:Methysergide maleate FDA label.png|none|450px]]
|fdaPatientInfo=Sansert® (methysergide maleate) is intended for use as a preventive agent in the treatment of vascular headaches. It should not be used for acute migraine attacks. If, after a 3-week trial period, Sansert® (methysergide maleate) has not been effective in decreasing the frequency or intensity of headaches, it is unlikely that longer administration of Sansert® (methysergide maleate) will be beneficial.
Patients should be advised to report the following symptoms immediately and to discontinue the drug: cold, numb, and painful hands and feet; leg cramps on walking; any type of girdle, flank, or chest pain; shortness of breath; or any associated symptomatology. There must be a drug-free interval of 3-4 weeks after each 6-month course of treatment.
Sansert® (methysergide maleate) should be taken with meals. Weight gain may necessitate modification of diet.
|alcohol=Alcohol-Methysergide interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.
}}
{{Methysergide}}
{{Drugbox
{{Drugbox
| Watchedfields = changed
| Watchedfields = changed
| verifiedrevid = 462251649
| 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
| 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 chemical structure.png
| width = 150
| width = 150
<!--Clinical data-->
<!--Clinical data-->
| tradename =
| tradename = Deseril, Sansert
| Drugs.com = {{drugs.com|CONS|methysergide}}
| Drugs.com = {{drugs.com|CONS|methysergide}}
| MedlinePlus = a603022
| MedlinePlus = a603022
| pregnancy_category = X
| pregnancy_AU = C
| pregnancy_US = X
| legal_AU = S4
| legal_CA = Rx-only
| legal_UK = POM
| legal_US = Rx-only
 
<!--Identifiers-->
<!--Identifiers-->
| CASNo_Ref = {{cascite|correct|CAS}}
| CASNo_Ref = {{cascite|correct|CAS}}
Line 128: Line 26:
| IUPHAR_ligand = 134
| IUPHAR_ligand = 134
| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| DrugBank = DB00247
| DrugBank = DB00247
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 9300
| ChemSpiderID = 9300
Line 137: Line 35:
| ChEMBL_Ref = {{ebicite|correct|EBI}}
| ChEMBL_Ref = {{ebicite|correct|EBI}}
| ChEMBL = 1065
| ChEMBL = 1065
<!--Chemical data-->
<!--Chemical data-->
| C=21 | H=27 | N=3 | O=2
| C=21 | H=27 | N=3 | O=2  
| molecular_weight = 353.458 g/mol
| 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
| smiles = O=C(N[C@@H](CC)CO)[C@@H]3/C=C2/c4cccc1c4c(cn1C)C[C@H]2N(C3)C
Line 147: Line 46:
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| StdInChIKey = KPJZHOPZRAFDTN-ZRGWGRIASA-N
| StdInChIKey = KPJZHOPZRAFDTN-ZRGWGRIASA-N
}}__NOTOC__
}}
 
__NOTOC__
{{CMG}}
{{CMG}}
{{SB}} Sansert<sup>®</sup>


==Overview==
==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.
'''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==
 
====Sansert (methysergide maleate) Tablet, Coated====
 
'''  [[Methysergide indications and usage|Indications and Usage]]'''
'''| [[Methysergide dosage and administration|Dosage and Administration]]'''
'''| [[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 how supplied storage and handling|How Supplied/Storage and Handling]]'''
'''| [[Methysergide patient counseling information|Patient Counseling Information]]'''
 
{|
| [[File:Ms01.png|800px|thumb]]
|}


==Medical uses==
==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.
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>
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==
==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.
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>
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==
==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>
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>


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>
==History==
 
Methysergide was approved by the [[Food and Drug Administration (United States)|U.S. Food and Drug Administration]] (FDA) in 1962.
==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}}


[[Novartis]] withdrew it from the U.S. market after taking over [[Sandoz]], but currently lists it as a product.
==Synthesis==
[[File:Methysergide synthesis.png|thumb|center|500px|Methysergide synthesis: [[Sandoz]] Ltd.]]


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


==References==
==References==
{{Reflist|2}}
{{Reflist|2}}


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.

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