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Identification
NameMethysergide
Accession NumberDB00247  (APRD00463)
TypeSmall Molecule
GroupsApproved
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
External Identifiers Not Available
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Sanserttablet2 mgoralNovartis Pharmaceuticals Canada Inc1962-12-312009-02-16Canada
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International Brands
NameCompany
DeserilNot Available
DesernilNot Available
Brand mixturesNot Available
Salts
Name/CASStructureProperties
Methysergide maleate
ThumbNot applicableDBSALT000895
Categories
UNIIXZA9HY6Z98
CAS number361-37-5
WeightAverage: 353.458
Monoisotopic: 353.210327123
Chemical FormulaC21H27N3O2
InChI KeyInChIKey=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[[email protected]](CN2C)C(=O)NC(CC)CO
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as lysergamides. These are amides of Lysergic acids.
KingdomOrganic compounds
Super ClassAlkaloids and derivatives
ClassErgoline and derivatives
Sub ClassLysergic acids and derivatives
Direct ParentLysergamides
Alternative Parents
Substituents
  • Lysergic acid amide
  • Indoloquinoline
  • Benzoquinoline
  • Quinoline-3-carboxamide
  • Pyrroloquinoline
  • Quinoline
  • Isoindole or derivatives
  • Indole or derivatives
  • Indole
  • Aralkylamine
  • Tetrahydropyridine
  • Benzenoid
  • Substituted pyrrole
  • N-methylpyrrole
  • Heteroaromatic compound
  • Pyrrole
  • Tertiary aliphatic amine
  • Tertiary amine
  • Secondary carboxylic acid amide
  • Carboxamide group
  • Azacycle
  • Organoheterocyclic compound
  • Carboxylic acid derivative
  • Carboxylic acid amide
  • Hydrocarbon derivative
  • Primary alcohol
  • Organooxygen compound
  • Organonitrogen compound
  • Carbonyl group
  • Amine
  • Alcohol
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors
Pharmacology
IndicationFor the treatment of vascular headache
PharmacodynamicsMethysergide 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 actionMethysergide 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.
Related Articles
AbsorptionRapid
Volume of distributionNot Available
Protein bindingNot Available
Metabolism

Hepatic

Route of eliminationNot Available
Half lifeNot Available
ClearanceNot Available
ToxicityFew 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
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
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 )
Pharmacoeconomics
Manufacturers
  • Novartis pharmaceuticals corp
Packagers
  • Novartis AG
  • Pharmaceutical Utilization Management Program VA Inc.
  • Professional Co.
Dosage forms
FormRouteStrength
Tabletoral2 mg
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.
PatentsNot Available
Properties
StateSolid
Experimental Properties
PropertyValueSource
melting point195 °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 RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
SpectraNot Available
References
Synthesis ReferenceNot Available
General ReferencesNot Available
External Links
ATC CodesN02CA04
AHFS Codes
  • 12:16.00
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Interactions
Drug InteractionsNot Available
Food InteractionsNot Available

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 change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors. Beta-arrestin family members inhibit signaling via G proteins ...
Gene Name:
HTR2B
Uniprot ID:
P41595
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-iodophenyl-2-aminopropane (DOI) and lysergic acid diethylamide (LSD). Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modul...
Gene Name:
HTR2C
Uniprot ID:
P28335
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-iodophenyl)-2-aminopropane (DOI) and lysergic acid diethylamide (LSD). Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates...
Gene Name:
HTR2A
Uniprot ID:
P28223
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 signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors, such as adenylate cyclase. Beta-arrestin family members inhibit signaling via G pro...
Gene Name:
HTR1A
Uniprot ID:
P08908
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 is mediated by G proteins that stimulate adenylate cyclase.
Gene Name:
HTR7
Uniprot ID:
P34969
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 substances, such as lysergic acid diethylamide (LSD). Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of ...
Gene Name:
HTR1B
Uniprot ID:
P28222
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 triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors, such as adenylate cyclase. Signaling inhibits adenylate cyclase activity.
Gene Name:
HTR1F
Uniprot ID:
P30939
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 triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors, such as adenylate cyclase. Signaling inhibits adenylate cyclase activity.
Gene Name:
HTR1E
Uniprot ID:
P28566
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 ]
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Drug created on June 13, 2005 07:24 / Updated on April 21, 2016 14:15