DrugBank: Ergotamine (DB00696)

targets (10) enzymes (2) transporters (1)

Identification

Name

Ergotamine

Accession Number

DB00696 (APRD00677)

Type

small molecule

Groups

approved

Description

A vasoconstrictor found in ergot of Central Europe. It is an alpha-1 selective adrenergic agonist and is commonly used in the treatment of migraine disorders. [PubChem]

Structure

Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure

Synonyms

Not Available

Salts

Not Available

Brand names

Name	Company
Ergomar
Ergostat
Ergotamin
Ergoton-A
Medihaler Ergotamine
Wigrettes

Brand mixtures

Brand Name	Ingredients
Bellergal Spacetabs	Belladonna + Ergotamine Tartrate + Phenobarbital
Bellergal Tab	Belladonna + Ergotamine (Ergotamine Tartrate) + Phenobarbital
Cafergot Pb Sup	Belladonna + Caffeine + Ergotamine (Ergotamine Tartrate) + Pentobarbital
Cafergot Pb Tab	Belladonna + Caffeine + Ergotamine (Ergotamine Tartrate) + Pentobarbital Sodium
Cafergot Sup	Caffeine + Ergotamine Tartrate
Cafergot Tab	Caffeine + Ergotamine Tartrate
Ergodryl Cap	Caffeine Citrate + Diphenhydramine Hydrochloride + Ergotamine Tartrate
Gravergol Capsules	Caffeine + Dimenhydrinate + Ergotamine Tartrate
Megral Tabs	Caffeine + Cyclizine Hydrochloride + Ergotamine Tartrate
Wigraine Suppositories	Belladonna + Caffeine + Ergotamine Tartrate
Wigraine Tab	Belladonna + Caffeine + Ergotamine Tartrate

Categories

Vasoconstrictor Agents
Sympatholytics
Adrenergic alpha-Agonists
Analgesics, Non-Narcotic

CAS number

113-15-5

Weight

Average: 581.6615
Monoisotopic: 581.263819255

Chemical Formula

C₃₃H₃₅N₅O₅

InChI Key

InChIKey=XCGSFFUVFURLIX-VFGNJEKYSA-N

InChI

InChI=1S/C33H35N5O5/c1-32(35-29(39)21-15-23-22-10-6-11-24-28(22)20(17-34-24)16-25(23)36(2)18-21)31(41)38-26(14-19-8-4-3-5-9-19)30(40)37-13-7-12-27(37)33(38,42)43-32/h3-6,8-11,15,17,21,25-27,34,42H,7,12-14,16,18H2,1-2H3,(H,35,39)/t21-,25-,26+,27+,32-,33+/m1/s1

Plain Text

IUPAC Name

(4R,7R)-N-[(1S,2S,4R,7S)-7-benzyl-2-hydroxy-4-methyl-5,8-dioxo-3-oxa-6,9-diazatricyclo[7.3.0.0^{2,6}]dodecan-4-yl]-6-methyl-6,11-diazatetracyclo[7.6.1.0^{2,7}.0^{12,16}]hexadeca-1(16),2,9,12,14-pentaene-4-carboxamide

SMILES

[H][C@@]12CCCN1C(=O)[C@H](CC1=CC=CC=C1)N1C(=O)[C@](C)(NC(=O)[C@H]3CN(C)[C@]4([H])CC5=CNC6=CC=CC(=C56)C4=C3)O[C@@]21O

Plain Text

Mass Spec

show (12 KB)

Taxonomy

Kingdom

Organic

Classes

Alkaloids and Alkaloid Derivatives
Lactams

Substructures

Ergolines
Hydroxy Compounds
Alkanes and Alkenes
Indoles and Indole Derivatives
Carboxylic Acids and Derivatives
Amino Ketones
Phenylpropenes
Pyrroles
Piperazines
Pyrrolidines
Ethers
Benzene and Derivatives
Aliphatic and Aryl Amines
Alkaloids and Alkaloid Derivatives
Isoprenes
Phenethylamines
Heterocyclic compounds
Aromatic compounds
Carboxamides and Derivatives
Phenylpropylamines
Tryptamines and Derivatives
Lactams
Pyrrolopyrazines
Amphetamines
Indoloquinolines

Pharmacology

Indication

For use as therapy to abort or prevent vascular headache, e.g., migraine, migraine variants, or so called "histaminic cephalalgia".

Pharmacodynamics

Ergotamine is a vasoconstrictor and alpha adrenoreceptor antagonist. The pharmacological properties of ergotamine are extremely complex; some of its actions are unrelated to each other, and even mutually antagonistic. The drug has partial agonist and/or antagonist activity against tryptaminergic, dopaminergic and alpha adrenergic receptors depending upon their site, and it is a highly active uterine stimulant. It causes constriction of peripheral and cranial blood vessels and produces depression of central vasomotor centers. The pain of a migraine attack is believed to be due to greatly increased amplitude of pulsations in the cranial arteries, especially the meningeal branches of the external carotid artery. Ergotamine reduces extracranial blood flow, causes a decline in the amplitude of pulsation in the cranial arteries, and decreases hyperperfusion of the territory of the basilar artery. It does not reduce cerebral hemispheric blood flow.

Mechanism of action

Ergotamine acts on migraine by one of two proposed mechanisms: 1) activation of 5-HT_1D receptors located on intracranial blood vessels, including those on arterio-venous anastomoses, leads to vasoconstriction, which correlates with the relief of migraine headache, and 2) activation of 5-HT_1D receptors on sensory nerve endings of the trigeminal system results in the inhibition of pro-inflammatory neuropeptide release.

Absorption

The bioavailability of sublingually administered ergotamine has not been determined.

Volume of distribution

Not Available

Protein binding

Not Available

Metabolism

Hepatic. Ergotamine is metabolized by the liver by largely undefined pathways, and 90% of the metabolites are excreted in the bile.

Route of elimination

Not Available

Half life

2 hours

Clearance

Not Available

Toxicity

Signs of overexposure include irritation, nausea, vomiting, headache, diarrhea, thirst, coldness of skin, pruritus, weak pulse, numbness, tingling of extremities, and confusion.

Affected organisms

Humans and other mammals

Pathways

Not Available

Pharmacoeconomics

Manufacturers

3m pharmaceuticals inc
Rosedale therapeutics
Parke davis div warner lambert co
Organon usa inc

Packagers

Dosage forms

Form	Route	Strength
Tablet	Sublingual

Prices

Unit description	Cost	Unit
Ergotamine tartrate powder	224.35 USD	powder
Ergomar 2 mg tablet sl	8.97 USD	tablet
Migergot suppository	7.39 USD	suppository
Cafergot tablet	1.89 USD	tablet
Ergotamine-caffeine tablet	1.14 USD	tablet

DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.

Patents

Not Available

Properties

State

solid

Experimental Properties

Property	Value	Source
melting point	213.5 dec °C	PhysProp
water solubility	Slight	Not Available
logP	2	Not Available

Predicted Properties

Property	Value	Source
water solubility	2.23e-01 g/l	ALOGPS
logP	2.95	ALOGPS
logP	2.6	ChemAxon
logS	-3.4	ALOGPS
pKa (strongest acidic)	9.7	ChemAxon
pKa (strongest basic)	7.78	ChemAxon
physiological charge	1	ChemAxon
hydrogen acceptor count	6	ChemAxon
hydrogen donor count	3	ChemAxon
polar surface area	118.21	ChemAxon
rotatable bond count	4	ChemAxon
refractivity	160.17	ChemAxon
polarizability	61.69	ChemAxon

References

Synthesis Reference

Not Available

General Reference

Tfelt-Hansen P, Saxena PR, Dahlof C, Pascual J, Lainez M, Henry P, Diener H, Schoenen J, Ferrari MD, Goadsby PJ: Ergotamine in the acute treatment of migraine: a review and European consensus. Brain. 2000 Jan;123 ( Pt 1):9-18. Pubmed
Schardl CL, Panaccione DG, Tudzynski P: Ergot alkaloids—biology and molecular biology. Alkaloids Chem Biol. 2006;63:45-86. Pubmed

External Links

Resource	Link
KEGG Compound	C07544
PubChem Compound	8223
PubChem Substance	46507632
ChemSpider	7930
Therapeutic Targets Database	DAP000141
PharmGKB	PA164747651
Drug Product Database	328952
RxList	http://www.rxlist.com/cgi/generic2/ergotamine.htm
Drugs.com	http://www.drugs.com/cdi/ergotamine.html
PDRhealth	http://www.pdrhealth.com/drug_info/rxdrugprofiles/drugs/caf1060.shtml
Wikipedia	http://en.wikipedia.org/wiki/Ergotamine

ATC Codes

N02CA01
N02CA02

AHFS Codes

Not Available

PDB Entries

Not Available

FDA label

Not Available

MSDS

show (53.1 KB)

Interactions

Drug Interactions

Drug	Interaction
Acebutolol	Ischemia with risk of gangrene
Almotriptan	Possible severe and prolonged vasoconstriction
Amprenavir	Amprenavir may increase the effect and toxicity of ergotamine.
Amyl Nitrite	Possible antagonism of action
Atazanavir	Atazanavir may increase the effect and toxicity of ergotamine.
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
Desvenlafaxine	Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
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
Fluconazole	Possible ergotism and severe ischemia with this combination
Fluoxetine	Possible ergotism and severe ischemia with this combination
Fluvoxamine	Possible ergotism and severe ischemia with this combination
Fosamprenavir	Amprenavir increases the effect and toxicity of ergot derivative
Frovatriptan	Possible severe and prolonged vasoconstriction
Indinavir	Indinavir may increase the serum concentration of ergotamine. Concomitant therapy is contraindicated.
Isosorbide Dinitrate	Possible antagonism of action
Isosorbide Mononitrate	Possible antagonism of action
Itraconazole	Possible ergotism and severe ischemia with this combination
Josamycin	Possible ergotism and severe ischemia with this combination
Ketoconazole	Possible ergotism and severe ischemia with this combination.
Labetalol	Ischemia with risk of gangrene
Lorcaserin	Avoid all combinations with any ergot derivative such as ergotamine. The combination can increase the risk of developing serotonin syndrome and/or valvular heart disease.
Metoprolol	Ischemia with risk of gangrene
Nadolol	Ischemia with risk of gangrene
Naratriptan	Possible severe and prolonged vasoconstriction.
Nefazodone	Possible ergotism and severe ischemia with this combination
Nelfinavir	Nelfinavir increases the effect and toxicity of ergot derivative
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
Ritonavir	The protease inhibitor, ritonavir, may increase the effect and toxicity of the ergot derivative, ergotamine.
Rizatriptan	Possible severe and prolonged vasoconstriction
Saquinavir	The protease inhibitor, saquinavir, may increase the effect and toxicity of the ergot derivative, ergotamine.
Sibutramine	Possible serotoninergic syndrome with this combination
Sotalol	Ischemia with risk of gangrene
Sumatriptan	Possible severe and prolonged vasoconstriction
Telaprevir	Telaprevir increases levels by affecting CYP3A4 metabolism. Concomitant therapy is contraindicated.
Telithromycin	Telithromycin may reduce clearance of Ergotamine. Concomitant therapy is contraindicated.
Timolol	Ischemia with risk of gangrene
Tipranavir	Tipranavir, co-administered with Ritonavir, may increase the plasma concentration of Ergotamine. Concomitant therapy is contraindicated.
Tramadol	Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
Tranylcypromine	Increased risk of serotonin syndrome. Use caution during concomitant therapy and monitor for symptoms of serotonin syndrome.
Trazodone	Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
Trimipramine	Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
Troleandomycin	Possible ergotism and severe ischemia with this combination
Venlafaxine	Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
Voriconazole	Voriconazole, a strong CYP3A4 inhibitor, may increase the serum concentration of ergotamine by decreasing its metabolism. Concomitant therapy is contraindicated.
Zileuton	Possible ergotism and severe ischemia with this combination
Zolmitriptan	Concomitant use of the serotonin 5-HT1D receptor agonist, zolmitriptan, and the ergot derivative, ergotamine, may result in additive vasoconstrictive effects. Concomitant use within 24 hours is contraindicated.

Food Interactions

Caffeine increases absorption.
Take without regard to meals.

Targets
1. 5-hydroxytryptamine 1D 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: P28221 Gene: HTR1D Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: Silberstein SD, McCrory DC: Ergotamine and dihydroergotamine: history, pharmacology, and efficacy. Headache. 2003 Feb;43(2):144-66. Pubmed Lovenberg TW, Erlander MG, Baron BM, Racke M, Slone AL, Siegel BW, Craft CM, Burns JE, Danielson PE, Sutcliffe JG: Molecular cloning and functional expression of 5-HT1E-like rat and human 5-hydroxytryptamine receptor genes. Proc Natl Acad Sci U S A. 1993 Mar 15;90(6):2184-8. Pubmed Hoyer D, Lery H, Waeber C, Bruinvels AT, Nozulak J, Palacios JM: “5-HT1R” or 5-HT1D sites? Evidence for 5-HT1D binding sites in rabbit brain. Naunyn Schmiedebergs Arch Pharmacol. 1992 Sep;346(3):249-54. Pubmed Sanchez-Lopez A, Centurion D, Vazquez E, Arulmani U, Saxena PR, Villalon CM: Pharmacological profile of the 5-HT-induced inhibition of cardioaccelerator sympathetic outflow in pithed rats: correlation with 5-HT1 and putative 5-ht5A/5B receptors. Br J Pharmacol. 2003 Oct;140(4):725-35. Epub 2003 Sep 22. Pubmed Deliganis AV, Peroutka SJ: 5-Hydroxtryptamine1D receptor agonism predicts antimigraine efficacy. Headache. 1991 Apr;31(4):228-31. Pubmed 2. 5-hydroxytryptamine 1B 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: P28222 Gene: HTR1B Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: Villalon CM, De Vries P, Rabelo G, Centurion D, Sanchez-Lopez A, Saxena P: Canine external carotid vasoconstriction to methysergide, ergotamine and dihydroergotamine: role of 5-HT1B/1D receptors and alpha2-adrenoceptors. Br J Pharmacol. 1999 Feb;126(3):585-94. Pubmed Willems EW, Trion M, De Vries P, Heiligers JP, Villalon CM, Saxena PR: Pharmacological evidence that alpha1-and alpha2-adrenoceptors mediate vasoconstriction of carotid arteriovenous anastomoses in anaesthetized pigs. Br J Pharmacol. 1999 Jul;127(5):1263-71. Pubmed Cohen ML, Schenck K: Contractile responses to sumatriptan and ergotamine in the rabbit saphenous vein: effect of selective 5-HT receptor agonists and PGF. Br J Pharmacol. 2000 Oct;131(3):562-8. Pubmed Valdivia LF, Centurion D, Arulmani U, Saxena PR, Villalon CM: 5-HT1B receptors, alpha2A/2C- and, to a lesser extent, alpha1-adrenoceptors mediate the external carotid vasoconstriction to ergotamine in vagosympathectomised dogs. Naunyn Schmiedebergs Arch Pharmacol. 2004 Jul;370(1):46-53. Epub 2004 Jun 29. Pubmed 3. 5-hydroxytryptamine 2A 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. 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 Gene: HTR2A Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: Bom AH, Heiligers JP, Saxena PR, Verdouw PD: Reduction of cephalic arteriovenous shunting by ergotamine is not mediated by 5-HT1-like or 5-HT2 receptors. Br J Pharmacol. 1989 Jun;97(2):383-90. Pubmed Panconesi A, Anselmi B, Curradi C, Perfetto F, Piluso A, Franchi G: Comparison between venoconstrictor effects of sumatriptan and ergotamine in migraine patients. Headache. 1994 Apr;34(4):194-7. Pubmed Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed 4. D(2) dopamine receptor Pharmacological action: unknown Actions: agonist This is one of the five types (D1 to D5) of receptors for dopamine. The activity of this receptor is mediated by G proteins which inhibit adenylyl cyclase Organism class: human UniProt ID: P14416 Gene: DRD2 Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: Verhoeff NP, Visser WH, Ferrari MD, Saxena PR, van Royen EA: Dopamine D2-receptor imaging with 123I-iodobenzamide SPECT in migraine patients abusing ergotamine: does ergotamine cross the blood brain barrier? Cephalalgia. 1993 Oct;13(5):325-9. Pubmed Larson BT, Samford MD, Camden JM, Piper EL, Kerley MS, Paterson JA, Turner JT: Ergovaline binding and activation of D2 dopamine receptors in GH4ZR7 cells. J Anim Sci. 1995 May;73(5):1396-400. Pubmed 5. Alpha-1A adrenergic receptor Pharmacological action: yes Actions: partial agonist This alpha-adrenergic receptor mediates its action by association with G proteins that activate a phosphatidylinositol- calcium second messenger system. Its effect is mediated by G(q) and G(11) proteins Organism class: human UniProt ID: P35348 Gene: ADRA1A Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed Gornemann T, Jahnichen S, Schurad B, Latte KP, Horowski R, Tack J, Flieger M, Pertz HH: Pharmacological properties of a wide array of ergolines at functional alpha(1)-adrenoceptor subtypes. Naunyn Schmiedebergs Arch Pharmacol. 2008 Jan;376(5):321-30. Epub 2007 Dec 8. Pubmed 6. Alpha-1B adrenergic receptor Pharmacological action: yes Actions: partial agonist This alpha-adrenergic receptor mediates its action by association with G proteins that activate a phosphatidylinositol- calcium second messenger system Organism class: human UniProt ID: P35368 Gene: ADRA1B Protein Sequence: FASTA SNPs: SNPJam Report References: Gornemann T, Jahnichen S, Schurad B, Latte KP, Horowski R, Tack J, Flieger M, Pertz HH: Pharmacological properties of a wide array of ergolines at functional alpha(1)-adrenoceptor subtypes. Naunyn Schmiedebergs Arch Pharmacol. 2008 Jan;376(5):321-30. Epub 2007 Dec 8. Pubmed 7. Alpha-1D adrenergic receptor Pharmacological action: yes Actions: partial agonist This alpha-adrenergic receptor mediates its effect through the influx of extracellular calcium Organism class: human UniProt ID: P25100 Gene: ADRA1D Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: Gornemann T, Jahnichen S, Schurad B, Latte KP, Horowski R, Tack J, Flieger M, Pertz HH: Pharmacological properties of a wide array of ergolines at functional alpha(1)-adrenoceptor subtypes. Naunyn Schmiedebergs Arch Pharmacol. 2008 Jan;376(5):321-30. Epub 2007 Dec 8. Pubmed 8. Alpha-2A adrenergic receptor Pharmacological action: unknown Actions: partial agonist Alpha-2 adrenergic receptors mediate the catecholamine- induced inhibition of adenylate cyclase through the action of G proteins. The rank order of potency for agonists of this receptor is oxymetazoline > clonidine > epinephrine > norepinephrine > phenylephrine > dopamine > p-synephrine > p-tyramine > serotonin = p-octopamine. For antagonists, the rank order is yohimbine > phentolamine = mianserine > chlorpromazine = spiperone = prazosin > propanolol > alprenolol = pindolol Organism class: human UniProt ID: P08913 Gene: ADRA2A Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed Gornemann T, Jahnichen S, Schurad B, Latte KP, Horowski R, Tack J, Flieger M, Pertz HH: Pharmacological properties of a wide array of ergolines at functional alpha(1)-adrenoceptor subtypes. Naunyn Schmiedebergs Arch Pharmacol. 2008 Jan;376(5):321-30. Epub 2007 Dec 8. Pubmed 9. Alpha-2B adrenergic receptor Pharmacological action: unknown Actions: agonist, partial agonist Alpha-2 adrenergic receptors mediate the catecholamine- induced inhibition of adenylate cyclase through the action of G proteins. The rank order of potency for agonists of this receptor is clonidine > norepinephrine > epinephrine = oxymetazoline > dopamine > p-tyramine = phenylephrine > serotonin > p-synephrine / p-octopamine. For antagonists, the rank order is yohimbine > chlorpromazine > phentolamine > mianserine > spiperone > prazosin > alprenolol > propanolol > pindolol Organism class: human UniProt ID: P18089 Gene: ADRA2B Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed 10. Sodium-dependent noradrenaline transporter Pharmacological action: unknown Actions: inhibitor Amine transporter. Terminates the action of noradrenaline by its high affinity sodium-dependent reuptake into presynaptic terminals Organism class: human UniProt ID: P23975 Gene: SLC6A2 Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed

Targets

1. 5-hydroxytryptamine 1D 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: P28221 Link_out

Gene: HTR1D Link_out

Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:

Silberstein SD, McCrory DC: Ergotamine and dihydroergotamine: history, pharmacology, and efficacy. Headache. 2003 Feb;43(2):144-66. Pubmed
Lovenberg TW, Erlander MG, Baron BM, Racke M, Slone AL, Siegel BW, Craft CM, Burns JE, Danielson PE, Sutcliffe JG: Molecular cloning and functional expression of 5-HT1E-like rat and human 5-hydroxytryptamine receptor genes. Proc Natl Acad Sci U S A. 1993 Mar 15;90(6):2184-8. Pubmed
Hoyer D, Lery H, Waeber C, Bruinvels AT, Nozulak J, Palacios JM: “5-HT1R” or 5-HT1D sites? Evidence for 5-HT1D binding sites in rabbit brain. Naunyn Schmiedebergs Arch Pharmacol. 1992 Sep;346(3):249-54. Pubmed
Sanchez-Lopez A, Centurion D, Vazquez E, Arulmani U, Saxena PR, Villalon CM: Pharmacological profile of the 5-HT-induced inhibition of cardioaccelerator sympathetic outflow in pithed rats: correlation with 5-HT1 and putative 5-ht5A/5B receptors. Br J Pharmacol. 2003 Oct;140(4):725-35. Epub 2003 Sep 22. Pubmed
Deliganis AV, Peroutka SJ: 5-Hydroxtryptamine1D receptor agonism predicts antimigraine efficacy. Headache. 1991 Apr;31(4):228-31. Pubmed

2. 5-hydroxytryptamine 1B receptor

Pharmacological action: yes
Actions: agonist

Organism class: human
UniProt ID: P28222 Link_out

Gene: HTR1B Link_out

Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:

Villalon CM, De Vries P, Rabelo G, Centurion D, Sanchez-Lopez A, Saxena P: Canine external carotid vasoconstriction to methysergide, ergotamine and dihydroergotamine: role of 5-HT1B/1D receptors and alpha2-adrenoceptors. Br J Pharmacol. 1999 Feb;126(3):585-94. Pubmed
Willems EW, Trion M, De Vries P, Heiligers JP, Villalon CM, Saxena PR: Pharmacological evidence that alpha1-and alpha2-adrenoceptors mediate vasoconstriction of carotid arteriovenous anastomoses in anaesthetized pigs. Br J Pharmacol. 1999 Jul;127(5):1263-71. Pubmed
Cohen ML, Schenck K: Contractile responses to sumatriptan and ergotamine in the rabbit saphenous vein: effect of selective 5-HT receptor agonists and PGF. Br J Pharmacol. 2000 Oct;131(3):562-8. Pubmed
Valdivia LF, Centurion D, Arulmani U, Saxena PR, Villalon CM: 5-HT1B receptors, alpha2A/2C- and, to a lesser extent, alpha1-adrenoceptors mediate the external carotid vasoconstriction to ergotamine in vagosympathectomised dogs. Naunyn Schmiedebergs Arch Pharmacol. 2004 Jul;370(1):46-53. Epub 2004 Jun 29. Pubmed

3. 5-hydroxytryptamine 2A 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. 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:

Bom AH, Heiligers JP, Saxena PR, Verdouw PD: Reduction of cephalic arteriovenous shunting by ergotamine is not mediated by 5-HT1-like or 5-HT2 receptors. Br J Pharmacol. 1989 Jun;97(2):383-90. Pubmed
Panconesi A, Anselmi B, Curradi C, Perfetto F, Piluso A, Franchi G: Comparison between venoconstrictor effects of sumatriptan and ergotamine in migraine patients. Headache. 1994 Apr;34(4):194-7. Pubmed
Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed

4. D(2) dopamine receptor

Pharmacological action: unknown
Actions: agonist

This is one of the five types (D1 to D5) of receptors for dopamine. The activity of this receptor is mediated by G proteins which inhibit adenylyl cyclase

Organism class: human
UniProt ID: P14416 Link_out

Gene: DRD2 Link_out

Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:

Verhoeff NP, Visser WH, Ferrari MD, Saxena PR, van Royen EA: Dopamine D2-receptor imaging with 123I-iodobenzamide SPECT in migraine patients abusing ergotamine: does ergotamine cross the blood brain barrier? Cephalalgia. 1993 Oct;13(5):325-9. Pubmed
Larson BT, Samford MD, Camden JM, Piper EL, Kerley MS, Paterson JA, Turner JT: Ergovaline binding and activation of D2 dopamine receptors in GH4ZR7 cells. J Anim Sci. 1995 May;73(5):1396-400. Pubmed

5. Alpha-1A adrenergic receptor

Pharmacological action: yes
Actions: partial agonist

This alpha-adrenergic receptor mediates its action by association with G proteins that activate a phosphatidylinositol- calcium second messenger system. Its effect is mediated by G(q) and G(11) proteins

Organism class: human
UniProt ID: P35348 Link_out

Gene: ADRA1A Link_out

Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:

Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed
Gornemann T, Jahnichen S, Schurad B, Latte KP, Horowski R, Tack J, Flieger M, Pertz HH: Pharmacological properties of a wide array of ergolines at functional alpha(1)-adrenoceptor subtypes. Naunyn Schmiedebergs Arch Pharmacol. 2008 Jan;376(5):321-30. Epub 2007 Dec 8. Pubmed

6. Alpha-1B adrenergic receptor

Pharmacological action: yes
Actions: partial agonist

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

Organism class: human
UniProt ID: P35368 Link_out

Gene: ADRA1B Link_out

Protein Sequence: FASTA
SNPs: SNPJam Report Link_out

References:

Gornemann T, Jahnichen S, Schurad B, Latte KP, Horowski R, Tack J, Flieger M, Pertz HH: Pharmacological properties of a wide array of ergolines at functional alpha(1)-adrenoceptor subtypes. Naunyn Schmiedebergs Arch Pharmacol. 2008 Jan;376(5):321-30. Epub 2007 Dec 8. Pubmed

7. Alpha-1D adrenergic receptor

Pharmacological action: yes
Actions: partial agonist

This alpha-adrenergic receptor mediates its effect through the influx of extracellular calcium

Organism class: human
UniProt ID: P25100 Link_out

Gene: ADRA1D Link_out

Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:

Gornemann T, Jahnichen S, Schurad B, Latte KP, Horowski R, Tack J, Flieger M, Pertz HH: Pharmacological properties of a wide array of ergolines at functional alpha(1)-adrenoceptor subtypes. Naunyn Schmiedebergs Arch Pharmacol. 2008 Jan;376(5):321-30. Epub 2007 Dec 8. Pubmed

8. Alpha-2A adrenergic receptor

Pharmacological action: unknown
Actions: partial agonist

Alpha-2 adrenergic receptors mediate the catecholamine- induced inhibition of adenylate cyclase through the action of G proteins. The rank order of potency for agonists of this receptor is oxymetazoline > clonidine > epinephrine > norepinephrine > phenylephrine > dopamine > p-synephrine > p-tyramine > serotonin = p-octopamine. For antagonists, the rank order is yohimbine > phentolamine = mianserine > chlorpromazine = spiperone = prazosin > propanolol > alprenolol = pindolol

Organism class: human
UniProt ID: P08913 Link_out

Gene: ADRA2A Link_out

Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:

Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed
Gornemann T, Jahnichen S, Schurad B, Latte KP, Horowski R, Tack J, Flieger M, Pertz HH: Pharmacological properties of a wide array of ergolines at functional alpha(1)-adrenoceptor subtypes. Naunyn Schmiedebergs Arch Pharmacol. 2008 Jan;376(5):321-30. Epub 2007 Dec 8. Pubmed

9. Alpha-2B adrenergic receptor

Pharmacological action: unknown
Actions: agonist, partial agonist

Alpha-2 adrenergic receptors mediate the catecholamine- induced inhibition of adenylate cyclase through the action of G proteins. The rank order of potency for agonists of this receptor is clonidine > norepinephrine > epinephrine = oxymetazoline > dopamine > p-tyramine = phenylephrine > serotonin > p-synephrine / p-octopamine. For antagonists, the rank order is yohimbine > chlorpromazine > phentolamine > mianserine > spiperone > prazosin > alprenolol > propanolol > pindolol

Organism class: human
UniProt ID: P18089 Link_out

Gene: ADRA2B Link_out

Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:

Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed

10. Sodium-dependent noradrenaline transporter

Pharmacological action: unknown
Actions: inhibitor

Amine transporter. Terminates the action of noradrenaline by its high affinity sodium-dependent reuptake into presynaptic terminals

Organism class: human
UniProt ID: P23975 Link_out

Gene: SLC6A2 Link_out

Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:

Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. Pubmed

Enzymes
1. Cytochrome P450 3A4 Actions: substrate, inhibitor 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 reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4- hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. The enzyme also hydroxylates etoposide UniProt ID: P08684 Gene: CYP3A4 Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed 2. Cytochrome P450 1A2 Actions: substrate Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Most active in catalyzing 2-hydroxylation. Caffeine is metabolized primarily by cytochrome CYP1A2 in the liver through an initial N3-demethylation. Also acts in the metabolism of aflatoxin B1 and acetaminophen UniProt ID: P05177 Gene: CYP1A2 Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

Enzymes

1. Cytochrome P450 3A4

Actions: substrate, inhibitor

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 reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4- hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. The enzyme also hydroxylates etoposide

UniProt ID: P08684 Link_out

Gene: CYP3A4
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:

Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

2. Cytochrome P450 1A2

Actions: substrate

Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Most active in catalyzing 2-hydroxylation. Caffeine is metabolized primarily by cytochrome CYP1A2 in the liver through an initial N3-demethylation. Also acts in the metabolism of aflatoxin B1 and acetaminophen

UniProt ID: P05177 Link_out

Gene: CYP1A2
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:

Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

Transporters
1. Multidrug resistance protein 1 Actions: inhibitor Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells UniProt ID: P08183 Gene: ABCB1 Protein Sequence: FASTA Gene Sequence: FASTA SNPs: SNPJam Report References: Ekins S, Kim RB, Leake BF, Dantzig AH, Schuetz EG, Lan LB, Yasuda K, Shepard RL, Winter MA, Schuetz JD, Wikel JH, Wrighton SA: Three-dimensional quantitative structure-activity relationships of inhibitors of P-glycoprotein. Mol Pharmacol. 2002 May;61(5):964-73. Pubmed Yasuda K, Lan LB, Sanglard D, Furuya K, Schuetz JD, Schuetz EG: Interaction of cytochrome P450 3A inhibitors with P-glycoprotein. J Pharmacol Exp Ther. 2002 Oct;303(1):323-32. Pubmed

Transporters

1. Multidrug resistance protein 1

Actions: inhibitor

Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells

UniProt ID: P08183 Link_out

Gene: ABCB1 Link_out

Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:

Ekins S, Kim RB, Leake BF, Dantzig AH, Schuetz EG, Lan LB, Yasuda K, Shepard RL, Winter MA, Schuetz JD, Wikel JH, Wrighton SA: Three-dimensional quantitative structure-activity relationships of inhibitors of P-glycoprotein. Mol Pharmacol. 2002 May;61(5):964-73. Pubmed
Yasuda K, Lan LB, Sanglard D, Furuya K, Schuetz JD, Schuetz EG: Interaction of cytochrome P450 3A inhibitors with P-glycoprotein. J Pharmacol Exp Ther. 2002 Oct;303(1):323-32. Pubmed

Comments

Drug created on June 13, 2005 07:24 / Updated on February 08, 2013 16:19