DT-Web

DB00247 - Methysergide


Identification
Name Methysergide
Accession Number DB00247 (APRD00463)
Type small molecule
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
MOL SDF PDB SMILES InChI
Categories (*)
Molecular Weight 353.458
Groups approved
Monoisotopic Weight 353.210327123
Pharmacology
Indication For the treatment of vascular headache
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
Protein binding Not Available
Biotransformation Hepatic
Route of elimination 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
Interactions
Drug Interactions
Drug Mechanism of interaction
Acebutolol Ischemia with risk of gangrene
Almotriptan Possible severe and prolonged vasoconstriction
Amyl Nitrite Possible antagonism of action
Atenolol Ischemia with risk of gangrene
Betaxolol Ischemia with risk of gangrene
Bevantolol Ischemia with risk of gangrene
Bisoprolol Ischemia with risk of gangrene
Carteolol Ischemia with risk of gangrene
Carvedilol Ischemia with risk of gangrene
Clarithromycin Risk of ergotism and severe ischemia with this association
Delavirdine The antiretroviral agent may increase the ergot derivative toxicity
Efavirenz The antiretroviral agent may increase the ergot derivative toxicity
Eletriptan Possible severe and prolonged vasoconstriction
Erythrityl Tetranitrate Possible antagonism of action
Erythromycin Possible ergotism and severe ischemia with this combination
Esmolol Ischemia with risk of gangrene
Frovatriptan Possible severe and prolonged vasoconstriction
Isosorbide Dinitrate Possible antagonism of action
Isosorbide Mononitrate Possible antagonism of action
Josamycin Possible ergotism and severe ischemia with this combination
Labetalol Ischemia with risk of gangrene
Metoprolol Ischemia with risk of gangrene
Nadolol Ischemia with risk of gangrene
Naratriptan Possible severe and prolonged vasoconstriction.
Nitroglycerin Possible antagonism of action
Oxprenolol Ischemia with risk of gangrene
Penbutolol Ischemia with risk of gangrene
Pentaerythritol Tetranitrate Possible antagonism of action
Pindolol Ischemia with risk of gangrene
Posaconazole Contraindicated co-administration
Practolol Ischemia with risk of gangrene
Propranolol Ischemia with risk of gangrene
Rizatriptan Possible severe and prolonged vasoconstriction
Sibutramine Possible serotoninergic syndrome
Sotalol Ischemia with risk of gangrene
Sumatriptan Possible severe and prolonged vasoconstriction
Telithromycin Risk of ergotism and severe ischemia with this association
Timolol Ischemia with risk of gangrene
Troleandomycin Possible ergotism and severe ischemia with this combination
Zolmitriptan Possible severe and prolonged vasoconstriction
Food Interactions
  • Take with food to reduce irritation.

Targets


5-hydroxytryptamine 2B receptor
Name 5-hydroxytryptamine 2B receptor
Gene Name HTR2B
Pharmacological action yes
Actions antagonist
References
  • 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
DTHybrid score 0.2732
5-hydroxytryptamine 2C receptor
Name 5-hydroxytryptamine 2C receptor
Gene Name HTR2C
Pharmacological action yes
Actions antagonist
References
  • Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. - Pubmed
  • 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
DTHybrid score 0.3229
5-hydroxytryptamine 2A receptor
Name 5-hydroxytryptamine 2A receptor
Gene Name HTR2A
Pharmacological action yes
Actions antagonist
References
  • 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
  • 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
  • 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
  • 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
  • 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
  • Davidoff, R.A. (2002). _Migraine: Manifestations, pathogenesis, and management._ (p. 438). Oxford University Press, US. -
DTHybrid score 0.4098
5-hydroxytryptamine 1A receptor
Name 5-hydroxytryptamine 1A receptor
Gene Name HTR1A
Pharmacological action yes
Actions agonist
References
  • 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
  • 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
  • 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
  • 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
  • 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
DTHybrid score 0.3516
5-hydroxytryptamine 7 receptor
Name 5-hydroxytryptamine 7 receptor
Gene Name HTR7
Pharmacological action yes
Actions antagonist
References
  • 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
DTHybrid score 0.216

Predictions


Id Partner name Gene Name Score
831 D(2) dopamine receptor DRD2 0.2478
23 D(1A) dopamine receptor DRD1 0.1822
318 Alpha-2A adrenergic receptor ADRA2A 0.1659
4119 Cytochrome P450 2D6 CYP2D6 0.1652
638 D(3) dopamine receptor DRD3 0.1602
885 5-hydroxytryptamine 1B receptor HTR1B 0.1551
725 5-hydroxytryptamine 1D receptor HTR1D 0.1424
378 Alpha-2C adrenergic receptor ADRA2C 0.1416
4512 Cytochrome P450 3A4 CYP3A4 0.1342
432 D(4) dopamine receptor DRD4 0.132
629 Alpha-2B adrenergic receptor ADRA2B 0.1233
556 Alpha-1A adrenergic receptor ADRA1A 0.1199
824 Sodium-dependent serotonin transporter SLC6A4 0.1033
163 D(1B) dopamine receptor DRD5 0.1001
492 Histamine H1 receptor HRH1 0.0936
4200 Cytochrome P450 1A2 CYP1A2 0.0893
632 Alpha-1B adrenergic receptor ADRA1B 0.0872
103 Muscarinic acetylcholine receptor M1 CHRM1 0.0765
1588 Multidrug resistance protein 1 ABCB1 0.0756
1256 5-hydroxytryptamine 6 receptor HTR6 0.0661
617 Muscarinic acetylcholine receptor M2 CHRM2 0.058
51 Muscarinic acetylcholine receptor M3 CHRM3 0.0548
274 Muscarinic acetylcholine receptor M5 CHRM5 0.053
450 Muscarinic acetylcholine receptor M4 CHRM4 0.0515
540 Sodium-dependent noradrenaline transporter SLC6A2 0.0504
789 Alpha-1D adrenergic receptor ADRA1D 0.0478
528 5-hydroxytryptamine 1E receptor HTR1E 0.0469
4757 Cytochrome P450 2C9 CYP2C9 0.0456
6016 Cytochrome P450 2C19 CYP2C19 0.0437
94 5-hydroxytryptamine 4 receptor HTR4 0.0426
4118 Cytochrome P450 3A5 CYP3A5 0.0386
6107 Cytochrome P450 3A7 CYP3A7 0.0353
511 5-hydroxytryptamine 1F receptor HTR1F 0.0345
341 5-hydroxytryptamine 3 receptor HTR3A 0.034
193 Beta-1 adrenergic receptor ADRB1 0.0335
766 Beta-2 adrenergic receptor ADRB2 0.0328
6013 Cytochrome P450 2E1 CYP2E1 0.0291
587 Serum albumin ALB 0.028
1181 Alpha-1-acid glycoprotein 1 ORM1 0.0268
124 Histamine H2 receptor HRH2 0.0266
6145 Solute carrier family 22 member 1 SLC22A1 0.0261
3941 Amine oxidase [flavin-containing] A MAOA 0.0257
713 Sodium-dependent dopamine transporter SLC6A3 0.0256
131 Synaptic vesicular amine transporter SLC18A2 0.0222
6030 Cytochrome P450 2B6 CYP2B6 0.0204
734 D1 dopamine receptor-interacting protein calcyon CALY 0.0202
5718 Cytochrome P450 2A6 CYP2A6 0.0198
4924 Cytochrome P450 2C8 CYP2C8 0.0172
6025 UDP-glucuronosyltransferase 1-4 UGT1A4 0.0154
174 Sigma 1-type opioid receptor SIGMAR1 0.0146
6432 Transporter snf 0.0135
474 Acetylcholinesterase ACHE 0.0131
362 Melatonin receptor type 1B MTNR1B 0.0103
571 Melatonin receptor type 1A MTNR1A 0.0103
6101 Dimethylaniline monooxygenase [N-oxide-forming] 3 FMO3 0.0103
20 Prostaglandin G/H synthase 1 PTGS1 0.0102
6144 Solute carrier family 22 member 2 SLC22A2 0.0098
1517 Beta-3 adrenergic receptor ADRB3 0.0094
3923 Cholinesterase BCHE 0.009
750 Voltage-dependent calcium channel gamma-1 subunit CACNG1 0.0089
101 Potassium voltage-gated channel subfamily H member 2 KCNH2 0.0087
696 Kappa-type opioid receptor OPRK1 0.0086
904 Glutathione S-transferase P GSTP1 0.0085
6024 Cytochrome P450 1A1 CYP1A1 0.0081
6176 UDP-glucuronosyltransferase 1-3 UGT1A3 0.0078
923 Glutamate receptor 3 GRIA3 0.0075
1656 CYP2B protein CYP2B 0.0074
6106 Cytochrome P450 2C18 CYP2C18 0.0068
164 Histamine H4 receptor HRH4 0.0063
1632 Solute carrier organic anion transporter family member 2B1 SLCO2B1 0.0052
6104 Dimethylaniline monooxygenase [N-oxide-forming] 1 FMO1 0.0051
921 Glutamate receptor 2 GRIA2 0.0047
847 Mu-type opioid receptor OPRM1 0.0046
3426 Glutamine synthetase glnA 0.0043
3987 Glutamine synthetase GLUL 0.0043
467 Delta-type opioid receptor OPRD1 0.004
5878 Alpha-7 nicotinic cholinergic receptor subunit CHRFAM7A 0.0038
3876 Aromatic-L-amino-acid decarboxylase DDC 0.0037
1898 Cytochrome P450 1B1 CYP1B1 0.0036
6098 Potassium voltage-gated channel subfamily D member 2 KCND2 0.0032
6099 Potassium voltage-gated channel subfamily D member 3 KCND3 0.0032
6100 BDNF/NT-3 growth factors receptor NTRK2 0.0029
706 Glutamate [NMDA] receptor subunit 3A GRIN3A 0.0028
3939 Amine oxidase [flavin-containing] B MAOB 0.0028
872 Gamma-aminobutyric-acid receptor subunit alpha-1 GABRA1 0.0027
776 Bile salt export pump ABCB11 0.0027
1490 Solute carrier organic anion transporter family member 1B1 SLCO1B1 0.0025
6139 Solute carrier organic anion transporter family member 1A2 SLCO1A2 0.0025
1732 ATP-binding cassette sub-family G member 2 ABCG2 0.0024
1618 High affinity nerve growth factor receptor NTRK1 0.0023
1086 Potassium voltage-gated channel subfamily KQT member 2 KCNQ2 0.0021
858 Potassium voltage-gated channel subfamily A member 1 KCNA1 0.0017
464 Glutamate [NMDA] receptor subunit epsilon-2 GRIN2B 0.0017
5251 Carbonyl reductase [NADPH] 1 CBR1 0.0017
465 Calmodulin CALM1 0.0015
1360 Sphingomyelin phosphodiesterase SMPD1 0.0014
833 Organic cation/carnitine transporter 1 SLC22A4 0.0014
6147 Solute carrier family 22 member 3 SLC22A3 0.0014
6018 UDP-glucuronosyltransferase 1-9 UGT1A9 0.0013
118 Organic cation/carnitine transporter 2 SLC22A5 0.0006
↑