Identification

Name
Methysergide
Accession Number
DB00247  (APRD00463)
Type
Small Molecule
Groups
Approved
Description

An ergot derivative that is a congener of lysergic acid diethylamide. It antagonizes the effects of serotonin in blood vessels and gastrointestinal smooth muscle, but has few of the properties of other ergot alkaloids. Methysergide is used prophylactically in migraine and other vascular headaches and to antagonize serotonin in the carcinoid syndrome.

Structure
Thumb
Synonyms
  • (+)-9,10-Didehydro-N-(1-(hydroxymethyl)propyl)-1,6-dimethylergoline-8beta-carboxamide
  • (+)-N-(1-(Hydroxymethyl)propyl)-1-methyl-D-lysergamide
  • 1-Methyl-D-lysergic acid butanolamide
  • 1-Methyl-dextro-lysergic acid (+)-1-hydroxy-2-butylamide
  • 1-Methyllysergic acid butanolamide
  • 1-Methylmethylergonovine
  • 9,10-Didehydro-N-(1-(hydroxymethyl)propyl)-1,6-dimethylergoline-8-carboxamide
  • Methysergide
  • Methysergidum
  • Metisergida
  • Metisergido
  • N-(1-(Hydroxymethyl)propyl)-1-methyl-dextro-(+)-lysergamide
Product Ingredients
IngredientUNIICASInChI Key
Methysergide maleate2U7H1466GH129-49-7LWYXFDXUMVEZKS-ZVFOLQIPSA-N
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
SansertTablet2 mgOralNovartis1962-12-312009-02-16Canada
SansertTablet, coated2 mg/1OralNovartis1962-02-122008-09-17Us
International/Other Brands
Deseril / Desernil
Categories
UNII
XZA9HY6Z98
CAS number
361-37-5
Weight
Average: 353.458
Monoisotopic: 353.210327123
Chemical Formula
C21H27N3O2
InChI Key
KPJZHOPZRAFDTN-NQUBZZJWSA-N
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
IUPAC Name
(4R,7R)-N-(1-hydroxybutan-2-yl)-6,11-dimethyl-6,11-diazatetracyclo[7.6.1.0²,⁷.0¹²,¹⁶]hexadeca-1(15),2,9,12(16),13-pentaene-4-carboxamide
SMILES
[H][C@@]12CC3=CN(C)C4=C3C(=CC=C4)C1=C[C@H](CN2C)C(=O)NC(CC)CO

Pharmacology

Indication

For the treatment of vascular headache

Pharmacodynamics

Methysergide 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, as an intrinsic "motor hormone" of the gastrointestinal tract, and as a "hormone" involved in connective tissue reparative processes.

Mechanism of action

Methysergide is serotonin antagonists acts on central nervous system (CNS), which directly stimulates the smooth muscle leading to vasoconstriction. Some alpha-adrenergic blocking activity has been reported. Suggestions have been made by investigators as to the mechanism whereby Methysergide produces its clinical effects, but this has not been finally established, although it may be related to the antiserotonin effect.

TargetActionsOrganism
A5-hydroxytryptamine receptor 2B
antagonist
Human
A5-hydroxytryptamine receptor 2C
antagonist
Human
A5-hydroxytryptamine receptor 2A
antagonist
Human
A5-hydroxytryptamine receptor 1A
agonist
Human
A5-hydroxytryptamine receptor 7
antagonist
Human
U5-hydroxytryptamine receptor 1B
binder
Human
U5-hydroxytryptamine receptor 1F
binder
Human
U5-hydroxytryptamine receptor 1E
binder
Human
Absorption

Rapid

Volume of distribution
Not Available
Protein binding
Not Available
Metabolism

Hepatic

Route of elimination
Not Available
Half life
Not Available
Clearance
Not Available
Toxicity

Few cases of acute methysergide 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 methysergide. 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 methysergide.

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
(R)-warfarinThe metabolism of Methysergide can be decreased when combined with (R)-warfarin.
(S)-WarfarinThe metabolism of Methysergide can be decreased when combined with (S)-Warfarin.
2,5-Dimethoxy-4-ethylthioamphetamineThe risk or severity of adverse effects can be increased when Methysergide is combined with 2,5-Dimethoxy-4-ethylthioamphetamine.
3,4-MethylenedioxyamphetamineThe risk or severity of adverse effects can be increased when Methysergide is combined with 3,4-Methylenedioxyamphetamine.
3,5-diiodothyropropionic acidThe metabolism of Methysergide can be decreased when combined with 3,5-diiodothyropropionic acid.
4-Bromo-2,5-dimethoxyamphetamineThe risk or severity of adverse effects can be increased when Methysergide is combined with 4-Bromo-2,5-dimethoxyamphetamine.
4-hydroxycoumarinThe metabolism of 4-hydroxycoumarin can be decreased when combined with Methysergide.
4-MethoxyamphetamineMethysergide may increase the hypertensive and vasoconstricting activities of 4-Methoxyamphetamine.
5-androstenedioneThe metabolism of Methysergide can be decreased when combined with 5-androstenedione.
5-methoxy-N,N-dimethyltryptamineMethysergide may increase the vasoconstricting activities of 5-methoxy-N,N-dimethyltryptamine.
Food Interactions
  • Take with food to reduce irritation.

References

General References
Not Available
External Links
Human Metabolome Database
HMDB0014392
KEGG Drug
D02357
KEGG Compound
C07199
PubChem Compound
6540428
PubChem Substance
46506117
ChemSpider
5022813
BindingDB
50031942
ChEBI
584020
ChEMBL
CHEMBL485253
Therapeutic Targets Database
DAP000366
PharmGKB
PA164743265
IUPHAR
134
Guide to Pharmacology
GtP Drug Page
RxList
RxList Drug Page
Wikipedia
Methysergide
ATC Codes
N02CA04 — Methysergide

Clinical Trials

Clinical Trials
Not Available

Pharmacoeconomics

Manufacturers
  • Novartis pharmaceuticals corp
Packagers
  • Novartis AG
  • Pharmaceutical Utilization Management Program VA Inc.
  • Professional Co.
Dosage forms
FormRouteStrength
TabletOral2 mg
Tablet, coatedOral2 mg/1
Prices
Unit descriptionCostUnit
Methysergide maleate 100% powder2580.0USD g
Desyrel 100 mg tablet4.26USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)195 °CPhysProp
logP1.5Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.224 mg/mLALOGPS
logP2.22ALOGPS
logP1.82ChemAxon
logS-3.2ALOGPS
pKa (Strongest Acidic)15.01ChemAxon
pKa (Strongest Basic)7.85ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area57.5 Å2ChemAxon
Rotatable Bond Count4ChemAxon
Refractivity104.47 m3·mol-1ChemAxon
Polarizability40.41 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+1.0
Blood Brain Barrier+0.7015
Caco-2 permeable-0.8064
P-glycoprotein substrateSubstrate0.8396
P-glycoprotein inhibitor INon-inhibitor0.8782
P-glycoprotein inhibitor IINon-inhibitor0.7515
Renal organic cation transporterNon-inhibitor0.8129
CYP450 2C9 substrateNon-substrate0.8536
CYP450 2D6 substrateNon-substrate0.8474
CYP450 3A4 substrateSubstrate0.6889
CYP450 1A2 substrateNon-inhibitor0.791
CYP450 2C9 inhibitorNon-inhibitor0.9071
CYP450 2D6 inhibitorInhibitor0.8931
CYP450 2C19 inhibitorNon-inhibitor0.8867
CYP450 3A4 inhibitorNon-inhibitor0.8309
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9161
Ames testNon AMES toxic0.5241
CarcinogenicityNon-carcinogens0.8906
BiodegradationNot ready biodegradable0.8144
Rat acute toxicity3.3039 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9569
hERG inhibition (predictor II)Inhibitor0.6274
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as lysergamides. These are amides of Lysergic acids.
Kingdom
Organic compounds
Super Class
Alkaloids and derivatives
Class
Ergoline and derivatives
Sub Class
Lysergic acids and derivatives
Direct Parent
Lysergamides
Alternative Parents
Indoloquinolines / Benzoquinolines / Quinoline-3-carboxamides / Pyrroloquinolines / 3-alkylindoles / N-alkylindoles / Isoindoles and derivatives / Aralkylamines / N-methylpyrroles / Benzenoids
show 10 more
Substituents
Lysergic acid amide / Indoloquinoline / Benzoquinoline / Pyrroloquinoline / Quinoline-3-carboxamide / N-alkylindole / Quinoline / 3-alkylindole / Indole / Indole or derivatives
show 27 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
monocarboxylic acid amide, ergot alkaloid (CHEBI:584020)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Antagonist
General Function
Serotonin receptor activity
Specific Function
G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for various ergot alkaloid derivatives and psychoactive substances. Ligand binding causes a conformation...
Gene Name
HTR2B
Uniprot ID
P41595
Uniprot Name
5-hydroxytryptamine receptor 2B
Molecular Weight
54297.41 Da
References
  1. Schmuck K, Ullmer C, Kalkman HO, Probst A, Lubbert H: Activation of meningeal 5-HT2B receptors: an early step in the generation of migraine headache? Eur J Neurosci. 1996 May;8(5):959-67. [PubMed:8743744]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Antagonist
General Function
Serotonin receptor activity
Specific Function
G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for various drugs and psychoactive substances, including ergot alkaloid derivatives, 1-2,5,-dimethoxy-4-...
Gene Name
HTR2C
Uniprot ID
P28335
Uniprot Name
5-hydroxytryptamine receptor 2C
Molecular Weight
51820.705 Da
References
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]
  2. Johnson MP, Lea RA, Curtain RP, MacMillan JC, Griffiths LR: An investigation of the 5-HT2C receptor gene as a migraine candidate gene. Am J Med Genet B Neuropsychiatr Genet. 2003 Feb;117B(1):86-9. [PubMed:12555241]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Antagonist
General Function
Virus receptor activity
Specific Function
G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for various drugs and psychoactive substances, including mescaline, psilocybin, 1-(2,5-dimethoxy-4-iodop...
Gene Name
HTR2A
Uniprot ID
P28223
Uniprot Name
5-hydroxytryptamine receptor 2A
Molecular Weight
52602.58 Da
References
  1. Castilho VM, Avanzi V, Brandao ML: Antinociception elicited by aversive stimulation of the inferior colliculus. Pharmacol Biochem Behav. 1999 Mar;62(3):425-31. [PubMed:10080233]
  2. Geerts IS, Matthys KE, Herman AG, Bult H: Involvement of 5-HT1B receptors in collar-induced hypersensitivity to 5-hydroxytryptamine of the rabbit carotid artery. Br J Pharmacol. 1999 Jul;127(6):1327-36. [PubMed:10455282]
  3. Shaw AM, Brown C, Irvine J, Bunton DC, MacDonald A: Role of the 5-HT(2A)receptor and alpha(1)-adrenoceptor in the contractile response of rat pulmonary artery to 5-HT in the presence and absence of nitric oxide. Pulm Pharmacol Ther. 2000;13(6):277-85. [PubMed:11061982]
  4. Prins NH, Akkermans LM, Lefebvre RA, Schuurkes JA: Characterization of the receptors involved in the 5-HT-induced excitation of canine antral longitudinal muscle. Br J Pharmacol. 2001 Nov;134(6):1351-9. [PubMed:11704657]
  5. Connor JD, Rasheed H, Gilani AH, Cheema M, Rizvi Z, Saeed SA: Second messengers in platelet aggregation evoked by serotonin and A23187, a calcium ionophore. Life Sci. 2001 Oct 26;69(23):2759-64. [PubMed:11720080]
  6. Robert A. Davidoff (2002). Migraine : Manifestations, Pathogenesis, and Management (pp. 438). Oxford University Press. [ISBN:0198031351]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Agonist
General Function
Serotonin receptor activity
Specific Function
G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for various drugs and psychoactive substances. Ligand binding causes a conformation change that triggers...
Gene Name
HTR1A
Uniprot ID
P08908
Uniprot Name
5-hydroxytryptamine receptor 1A
Molecular Weight
46106.335 Da
References
  1. Scrogin KE, Johnson AK, Brooks VL: Methysergide delays the decompensatory responses to severe hemorrhage by activating 5-HT(1A) receptors. Am J Physiol Regul Integr Comp Physiol. 2000 Nov;279(5):R1776-86. [PubMed:11049861]
  2. Sugimoto Y, Inoue K, Yamada J: The tricyclic antidepressant clomipramine increases plasma glucose levels of mice. J Pharmacol Sci. 2003 Sep;93(1):74-9. [PubMed:14501155]
  3. Sugimoto Y, Inoue K, Yamada J: Involvement of 5-HT(2) receptor in imipramine-induced hyperglycemia in mice. Horm Metab Res. 2003 Sep;35(9):511-6. [PubMed:14517765]
  4. Skyba DA, Radhakrishnan R, Rohlwing JJ, Wright A, Sluka KA: Joint manipulation reduces hyperalgesia by activation of monoamine receptors but not opioid or GABA receptors in the spinal cord. Pain. 2003 Nov;106(1-2):159-68. [PubMed:14581123]
  5. Pranzatelli MR, Balletti J: Characterization of 5-hydroxytryptamine 1A-like binding sites in human ganglioneuroblastoma. Neurosci Lett. 1991 Oct 28;132(1):117-20. [PubMed:1838579]
Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Antagonist
General Function
Serotonin receptor activity
Specific Function
This is one of the several different receptors for 5-hydroxytryptamine (serotonin), a biogenic hormone that functions as a neurotransmitter, a hormone, and a mitogen. The activity of this receptor ...
Gene Name
HTR7
Uniprot ID
P34969
Uniprot Name
5-hydroxytryptamine receptor 7
Molecular Weight
53554.43 Da
References
  1. Sugimoto Y, Inoue K, Yamada J: The tricyclic antidepressant clomipramine increases plasma glucose levels of mice. J Pharmacol Sci. 2003 Sep;93(1):74-9. [PubMed:14501155]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Binder
General Function
Serotonin receptor activity
Specific Function
G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for ergot alkaloid derivatives, various anxiolytic and antidepressant drugs and other psychoactive subst...
Gene Name
HTR1B
Uniprot ID
P28222
Uniprot Name
5-hydroxytryptamine receptor 1B
Molecular Weight
43567.535 Da
References
  1. Matsumoto I, Combs MR, Jones DJ: Characterization of 5-hydroxytryptamine1B receptors in rat spinal cord via [125I]iodocyanopindolol binding and inhibition of [3H]-5-hydroxytryptamine release. J Pharmacol Exp Ther. 1992 Feb;260(2):614-26. [PubMed:1738111]
  2. Saxena PR, Tfel-Hansen P (2005). Triptans, 5-HT 1B/1D receptor agonists in the acute treatment of migraines. In Headaches (3rd ed., pp. 469-503, 459-467). Lippincott Williams & Wilkins. [ISBN:978-0781754002]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Binder
General Function
Serotonin receptor activity
Specific Function
G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for various alkaloids and psychoactive substances. Ligand binding causes a conformation change that trig...
Gene Name
HTR1F
Uniprot ID
P30939
Uniprot Name
5-hydroxytryptamine receptor 1F
Molecular Weight
41708.505 Da
References
  1. Adham N, Kao HT, Schecter LE, Bard J, Olsen M, Urquhart D, Durkin M, Hartig PR, Weinshank RL, Branchek TA: Cloning of another human serotonin receptor (5-HT1F): a fifth 5-HT1 receptor subtype coupled to the inhibition of adenylate cyclase. Proc Natl Acad Sci U S A. 1993 Jan 15;90(2):408-12. [PubMed:8380639]
  2. Saxena PR, Tfel-Hansen P (2005). Triptans, 5-HT 1B/1D receptor agonists in the acute treatment of migraines. In Headaches (3rd ed., pp. 469-503, 459-467). Lippincott Williams & Wilkins. [ISBN:978-0781754002]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Binder
General Function
Serotonin receptor activity
Specific Function
G-protein coupled receptor for 5-hydroxytryptamine (serotonin). Also functions as a receptor for various alkaloids and psychoactive substances. Ligand binding causes a conformation change that trig...
Gene Name
HTR1E
Uniprot ID
P28566
Uniprot Name
5-hydroxytryptamine receptor 1E
Molecular Weight
41681.57 Da
References
  1. Adham N, Kao HT, Schecter LE, Bard J, Olsen M, Urquhart D, Durkin M, Hartig PR, Weinshank RL, Branchek TA: Cloning of another human serotonin receptor (5-HT1F): a fifth 5-HT1 receptor subtype coupled to the inhibition of adenylate cyclase. Proc Natl Acad Sci U S A. 1993 Jan 15;90(2):408-12. [PubMed:8380639]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
No
Actions
Substrate
General Function
Vitamin d3 25-hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
Gene Name
CYP3A4
Uniprot ID
P08684
Uniprot Name
Cytochrome P450 3A4
Molecular Weight
57342.67 Da
References
  1. Marcucci C., Hutchens M., Wittwer E., Weingarten T., Sprung J., Nicholson W., Lalwani K., Metro D., Dull R., Swide C., Seagull F., Kirsch J. and Sandson N. (2015). A case approach to perioperative drug-drug interactions. Springer. [ISBN:978-1-4614-7495-1]

Drug created on June 13, 2005 07:24 / Updated on November 02, 2018 08:43