Banner
targets (5)
for drugs
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. [PubChem]
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
  • Methyllysergic acid butanolamide
  • Methysergid
  • Methysergidum [INN-Latin]
  • Metisergide [DCIT]
  • Metisergido [INN-Spanish]
  • N-(1-(Hydroxymethyl)propyl)-1-methyl-dextro-(+)-lysergamide
  • N-(alpha-(Hydroxymethyl)propyl)-1-methyl-dextro-lysergamide
Brand names
  • Deseril
  • Desernil
  • Desernyl
  • Deseryl
  • Sansert
Brand name mixtures Not Available
Categories
  • Vasoconstrictor Agents
  • Sympatholytics
  • Serotonin Antagonists
CAS number 361-37-5
Weight Average: 353.458
Monoisotopic: 353.210327123
Chemical Formula C21H27N3O2
InChI Key InChIKey=KPJZHOPZRAFDTN-ZRGWGRIASA-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
Plain Text
IUPAC Name
(4R,7R)-N-[(2S)-1-hydroxybutan-2-yl]-6,11-dimethyl-6,11-diazatetracyclo[7.6.1.0^{2,7}.0^{12,16}]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)N[C@@H](CC)CO
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Ergolines
  • Indoloquinolines
Substructures
  • Ergolines
  • Hydroxy Compounds
  • Alkanes and Alkenes
  • Indoles and Indole Derivatives
  • Amino Ketones
  • Phenylpropenes
  • Pyrroles
  • Benzene and Derivatives
  • Carboxylic Acids and Derivatives
  • Alcohols and Polyols
  • Aliphatic and Aryl Amines
  • Isoprenes
  • Phenethylamines
  • Heterocyclic compounds
  • Aromatic compounds
  • Carboxamides and Derivatives
  • Tryptamines and Derivatives
  • Amphetamines
  • Indoloquinolines
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.
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
Pharmacoeconomics
Manufacturers
  • Novartis pharmaceuticals corp
Packagers
  • Novartis AG
  • Pharmaceutical Utilization Management Program VA Inc.
  • Professional Co.
Dosage forms
Form Route Strength
Tablet Oral
Prices
Unit description Cost Unit
Methysergide maleate 100% powder 2580.0 USD g
Desyrel 100 mg tablet 4.26 USD tablet
Patents Not Available
Properties
State solid
Melting point 195 oC
Experimental Properties
Property Value Source
logP 1.5 PhysProp
Predicted Properties
Property Value Source
water solubility 2.24e-01 g/l ALOGPS
logP 2.22 ALOGPS
logP 1.82 ChemAxon Molconvert
logS -3.20 ALOGPS
pKa 16.00 ChemAxon Molconvert
hydrogen acceptor count 3 ChemAxon Molconvert
hydrogen donor count 2 ChemAxon Molconvert
polar surface area 57.50 ChemAxon Molconvert
rotatable bond count 4 ChemAxon Molconvert
refractivity 104.47 ChemAxon Molconvert
polarizability 41.08 ChemAxon Molconvert
References
Synthesis Reference Not Available
General Reference Not Available
External Links
Resource Link
KEGG Drug D02357 Link_out
KEGG Compound C07199 Link_out
PubChem Compound 9681 Link_out
PubChem Substance 46506117 Link_out
ChemSpider 9300 Link_out
BindingDB 50031942 Link_out
ChEBI 584020 Link_out
ChEMBL 584020 Link_out
Therapeutic Targets Database DAP000366 Link_out
PharmGKB PA450471 Link_out
Drug Product Database 27499 Link_out
RxList http://www.rxlist.com/cgi/generic3/sansert.htm Link_out
Wikipedia http://en.wikipedia.org/wiki/Methysergide Link_out
ATC Codes
  • N02CA04
AHFS Codes
  • 12:16.00
PDB Entries Not Available
FDA label Not Available
MSDS Not Available
Interactions
Drug Interactions Not Available
Food Interactions
  • Take with food to reduce irritation.
Targets

1. 5-hydroxytryptamine 2B receptor

Pharmacological action: yes
Actions: antagonist

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. This receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system

Organism class: human
UniProt ID: P41595 Link_out
Gene: HTR2B Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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

2. 5-hydroxytryptamine 2C receptor

Pharmacological action: yes
Actions: antagonist

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. This receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system

Organism class: human
UniProt ID: P28335 Link_out
Gene: HTR2C Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed
  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

3. 5-hydroxytryptamine 2A receptor

Pharmacological action: yes
Actions: antagonist

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. This receptor mediates its action by association with G proteins that activate a phosphatidylinositol-calcium second messenger system. This receptor is involved in tracheal smooth muscle contraction, bronchoconstriction, and control of aldosterone production

Organism class: human
UniProt ID: P28223 Link_out
Gene: HTR2A Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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
  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
  3. Shaw AM, Brown C, Irvine J, Bunton DC, MacDonald A: Role of the 5-HTreceptor 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
  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
  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
  6. Davidoff, R.A. (2002). Migraine: Manifestations, pathogenesis, and management. (p. 438). Oxford University Press, US.

4. 5-hydroxytryptamine 1A receptor

Pharmacological action: yes
Actions: agonist

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 inhibit adenylate cyclase activity

Organism class: human
UniProt ID: P08908 Link_out
Gene: HTR1A Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Scrogin KE, Johnson AK, Brooks VL: Methysergide delays the decompensatory responses to severe hemorrhage by activating 5-HT receptors. Am J Physiol Regul Integr Comp Physiol. 2000 Nov;279(5):R1776-86. Pubmed
  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
  3. Sugimoto Y, Inoue K, Yamada J: Involvement of 5-HT receptor in imipramine-induced hyperglycemia in mice. Horm Metab Res. 2003 Sep;35(9):511-6. Pubmed
  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
  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

5. 5-hydroxytryptamine 7 receptor

Pharmacological action: yes
Actions: antagonist

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

Organism class: human
UniProt ID: P34969 Link_out
Gene: HTR7 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

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
Comments
Drug created on June 13, 2005 07:24 / Updated on April 19, 2011 15:02

This project is supported by Genome Alberta & Genome Canada, a not-for-profit organization that is leading Canada's national genomics strategy with $600 million in funding from the federal government. This project is also supported in part by GenomeQuest, Inc., an enterprise genomic information company serving the life science community.