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Identification
NameLisuride
Accession NumberDB00589  (APRD00636)
TypeSmall Molecule
GroupsApproved
Description

An ergot derivative that acts as an agonist at dopamine D2 receptors (dopamine agonists). It may also act as an antagonist at dopamine D1 receptors, and as an agonist at some serotonin receptors (serotonin agonists). [PubChem]

Structure
Thumb
Synonyms
Lisurid
Lisurida
Lisuride
Lisuridum
N'-((8alpha)-9,10-didehydro-6-methylergolin-8-yl)-N,N-diethylurea
External Identifiers
  • MIP 2204
  • SH 31072 B
Approved Prescription ProductsNot Available
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International Brands
NameCompany
ArolacLisapharm
DipergonBayer
DoperginBayer
DopergineBayer Santé
ProclacamNot Available
RevanilNot Available
Brand mixturesNot Available
Salts
Name/CASStructureProperties
Lysuride Maleate
ThumbNot applicableDBSALT001034
Categories
UNIIE0QN3D755O
CAS number18016-80-3
WeightAverage: 338.4466
Monoisotopic: 338.210661474
Chemical FormulaC20H26N4O
InChI KeyInChIKey=BKRGVLQUQGGVSM-KBXCAEBGSA-N
InChI
InChI=1S/C20H26N4O/c1-4-24(5-2)20(25)22-14-10-16-15-7-6-8-17-19(15)13(11-21-17)9-18(16)23(3)12-14/h6-8,10-11,14,18,21H,4-5,9,12H2,1-3H3,(H,22,25)/t14-,18+/m0/s1
IUPAC Name
3,3-diethyl-1-[(4S,7R)-6-methyl-6,11-diazatetracyclo[7.6.1.0²,⁷.0¹²,¹⁶]hexadeca-1(16),2,9,12,14-pentaen-4-yl]urea
SMILES
[H][C@@]12CC3=CNC4=CC=CC(=C34)C1=C[C@@H](CN2C)NC(=O)N(CC)CC
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as indoloquinolines. These are polycyclic aromatic compounds containing an indole fused to a quinoline.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassQuinolines and derivatives
Sub ClassIndoloquinolines
Direct ParentIndoloquinolines
Alternative Parents
Substituents
  • Indoloquinoline
  • Ergoline skeleton
  • Benzoquinoline
  • Pyrroloquinoline
  • Alkaloid or derivatives
  • Isoindole or derivatives
  • Indole or derivatives
  • Indole
  • Aralkylamine
  • Tetrahydropyridine
  • Benzenoid
  • Heteroaromatic compound
  • Pyrrole
  • Urea
  • Tertiary aliphatic amine
  • Tertiary amine
  • Azacycle
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organonitrogen compound
  • Amine
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors
Pharmacology
IndicationFor the management of Parkinson's Disease
PharmacodynamicsNot Available
Mechanism of actionLisuride is an anti-Parkinson drug chemically related to the dopaminergic ergoline Parkinson's drugs. Lisuride binds to the 5-HT(1A) and 5-HT(2A/2C) receptors. It is also thought to bind to the dopamine receptor and to act as a dopamine agonist. Evidence has also emerged that Lisuride also binds to the Histamine H1 receptor. Lisuride is also used to lower prolactin and, in low doses, to prevent migraine attacks.
Related Articles
AbsorptionNot Available
Volume of distributionNot Available
Protein bindingabout 15%
MetabolismNot Available
Route of eliminationNot Available
Half lifeNot Available
ClearanceNot Available
ToxicityNot Available
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+0.9382
Caco-2 permeable-0.6106
P-glycoprotein substrateSubstrate0.9135
P-glycoprotein inhibitor IInhibitor0.7002
P-glycoprotein inhibitor IIInhibitor0.7091
Renal organic cation transporterNon-inhibitor0.6231
CYP450 2C9 substrateNon-substrate0.8394
CYP450 2D6 substrateSubstrate0.8919
CYP450 3A4 substrateSubstrate0.7279
CYP450 1A2 substrateInhibitor0.9107
CYP450 2C9 inhibitorNon-inhibitor0.9071
CYP450 2D6 inhibitorInhibitor0.8931
CYP450 2C19 inhibitorNon-inhibitor0.9025
CYP450 3A4 inhibitorInhibitor0.7959
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.5131
Ames testNon AMES toxic0.5
CarcinogenicityNon-carcinogens0.9156
BiodegradationNot ready biodegradable0.9797
Rat acute toxicity3.1801 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.572
hERG inhibition (predictor II)Inhibitor0.617
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage formsNot Available
PricesNot Available
PatentsNot Available
Properties
StateSolid
Experimental Properties
PropertyValueSource
logP2.2Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.14 mg/mLALOGPS
logP2.37ALOGPS
logP2.17ChemAxon
logS-3.4ALOGPS
pKa (Strongest Acidic)15.36ChemAxon
pKa (Strongest Basic)6.88ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area51.37 Å2ChemAxon
Rotatable Bond Count3ChemAxon
Refractivity101.81 m3·mol-1ChemAxon
Polarizability38.81 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
Spectra
Spectrum TypeDescriptionSplash Key
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, NegativeNot Available
References
Synthesis ReferenceNot Available
General ReferencesNot Available
External Links
ATC CodesG02CB02N02CA07
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Interactions
Drug InteractionsNot Available
Food InteractionsNot Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
agonist
General Function:
Potassium channel regulator activity
Specific Function:
Dopamine receptor whose activity is mediated by G proteins which inhibit adenylyl cyclase.
Gene Name:
DRD2
Uniprot ID:
P14416
Molecular Weight:
50618.91 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. Kvernmo T, Houben J, Sylte I: Receptor-binding and pharmacokinetic properties of dopaminergic agonists. Curr Top Med Chem. 2008;8(12):1049-67. [PubMed:18691132 ]
Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
agonist
General Function:
G-protein coupled amine receptor activity
Specific Function:
Dopamine receptor whose activity is mediated by G proteins which inhibit adenylyl cyclase. Promotes cell proliferation.
Gene Name:
DRD3
Uniprot ID:
P35462
Molecular Weight:
44224.335 Da
References
  1. Kvernmo T, Houben J, Sylte I: Receptor-binding and pharmacokinetic properties of dopaminergic agonists. Curr Top Med Chem. 2008;8(12):1049-67. [PubMed:18691132 ]
Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
agonist
General Function:
Sh3 domain binding
Specific Function:
Dopamine receptor responsible for neuronal signaling in the mesolimbic system of the brain, an area of the brain that regulates emotion and complex behavior. Its activity is mediated by G proteins which inhibit adenylyl cyclase. Modulates the circadian rhythm of contrast sensitivity by regulating the rhythmic expression of NPAS2 in the retinal ganglion cells (By similarity).
Gene Name:
DRD4
Uniprot ID:
P21917
Molecular Weight:
48359.86 Da
References
  1. Kvernmo T, Houben J, Sylte I: Receptor-binding and pharmacokinetic properties of dopaminergic agonists. Curr Top Med Chem. 2008;8(12):1049-67. [PubMed:18691132 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
antagonist
General Function:
G-protein coupled amine receptor activity
Specific Function:
Dopamine receptor whose activity is mediated by G proteins which activate adenylyl cyclase.
Gene Name:
DRD1
Uniprot ID:
P21728
Molecular Weight:
49292.765 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284 ]
  2. 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:17016423 ]
  3. Kvernmo T, Houben J, Sylte I: Receptor-binding and pharmacokinetic properties of dopaminergic agonists. Curr Top Med Chem. 2008;8(12):1049-67. [PubMed:18691132 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
antagonist
General Function:
G-protein coupled amine receptor activity
Specific Function:
Dopamine receptor whose activity is mediated by G proteins which activate adenylyl cyclase.
Gene Name:
DRD5
Uniprot ID:
P21918
Molecular Weight:
52950.5 Da
References
  1. Kvernmo T, Houben J, Sylte I: Receptor-binding and pharmacokinetic properties of dopaminergic agonists. Curr Top Med Chem. 2008;8(12):1049-67. [PubMed:18691132 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
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. Kimura K, Akai T, Nakamura K, Yamaguchi M, Nakagawa H, Oshino N: Dual activation by lisuride of central serotonin 5-HT(1A) and dopamine D(2) receptor sites: drug discrimination and receptor binding studies. Behav Pharmacol. 1991 Apr;2(2):105-112. [PubMed:11224054 ]
  2. Kvernmo T, Houben J, Sylte I: Receptor-binding and pharmacokinetic properties of dopaminergic agonists. Curr Top Med Chem. 2008;8(12):1049-67. [PubMed:18691132 ]
  3. Marona-Lewicka D, Kurrasch-Orbaugh DM, Selken JR, Cumbay MG, Lisnicchia JG, Nichols DE: Re-evaluation of lisuride pharmacology: 5-hydroxytryptamine1A receptor-mediated behavioral effects overlap its other properties in rats. Psychopharmacology (Berl). 2002 Oct;164(1):93-107. Epub 2002 Jul 19. [PubMed:12373423 ]
  4. Akai T, Takahashi M, Nakada Y, Ohnishi R, Ikoma Y, Yamaguchi M: [Anxiolytic effects of lisuride and its agonistic action to central 5-HT1A receptors]. Nihon Yakurigaku Zasshi. 1991 Apr;97(4):209-20. [PubMed:1678728 ]
  5. Miyazawa T, Murayama C, Nakagawa H: [Effect of lisuride on experimental cerebral infarction in rats]. Nihon Yakurigaku Zasshi. 1991 Dec;98(6):449-56. [PubMed:1783326 ]
  6. Cunningham KA, Callahan PM, Appel JB: Discriminative stimulus properties of 8-hydroxy-2-(di-n-propylamino)tetralin (8-OHDPAT): implications for understanding the actions of novel anxiolytics. Eur J Pharmacol. 1987 Jun 12;138(1):29-36. [PubMed:2887435 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
agonist
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. 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 c...
Gene Name:
HTR1D
Uniprot ID:
P28221
Molecular Weight:
41906.38 Da
References
  1. Kvernmo T, Houben J, Sylte I: Receptor-binding and pharmacokinetic properties of dopaminergic agonists. Curr Top Med Chem. 2008;8(12):1049-67. [PubMed:18691132 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
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. Kvernmo T, Houben J, Sylte I: Receptor-binding and pharmacokinetic properties of dopaminergic agonists. Curr Top Med Chem. 2008;8(12):1049-67. [PubMed:18691132 ]
Kind
Protein
Organism
Human
Pharmacological action
yes
Actions
agonist
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. Kvernmo T, Houben J, Sylte I: Receptor-binding and pharmacokinetic properties of dopaminergic agonists. Curr Top Med Chem. 2008;8(12):1049-67. [PubMed:18691132 ]
  2. Egan CT, Herrick-Davis K, Miller K, Glennon RA, Teitler M: Agonist activity of LSD and lisuride at cloned 5HT2A and 5HT2C receptors. Psychopharmacology (Berl). 1998 Apr;136(4):409-14. [PubMed:9600588 ]
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, 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. Kvernmo T, Houben J, Sylte I: Receptor-binding and pharmacokinetic properties of dopaminergic agonists. Curr Top Med Chem. 2008;8(12):1049-67. [PubMed:18691132 ]
  2. Egan CT, Herrick-Davis K, Miller K, Glennon RA, Teitler M: Agonist activity of LSD and lisuride at cloned 5HT2A and 5HT2C receptors. Psychopharmacology (Berl). 1998 Apr;136(4):409-14. [PubMed:9600588 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
agonist
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. Kvernmo T, Houben J, Sylte I: Receptor-binding and pharmacokinetic properties of dopaminergic agonists. Curr Top Med Chem. 2008;8(12):1049-67. [PubMed:18691132 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
other/unknown
General Function:
Thioesterase binding
Specific Function:
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 = mianser...
Gene Name:
ADRA2A
Uniprot ID:
P08913
Molecular Weight:
48956.275 Da
References
  1. Kvernmo T, Houben J, Sylte I: Receptor-binding and pharmacokinetic properties of dopaminergic agonists. Curr Top Med Chem. 2008;8(12):1049-67. [PubMed:18691132 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
other/unknown
General Function:
Epinephrine binding
Specific Function:
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 > phent...
Gene Name:
ADRA2B
Uniprot ID:
P18089
Molecular Weight:
49565.8 Da
References
  1. Kvernmo T, Houben J, Sylte I: Receptor-binding and pharmacokinetic properties of dopaminergic agonists. Curr Top Med Chem. 2008;8(12):1049-67. [PubMed:18691132 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
other/unknown
General Function:
Protein homodimerization activity
Specific Function:
Alpha-2 adrenergic receptors mediate the catecholamine-induced inhibition of adenylate cyclase through the action of G proteins.
Gene Name:
ADRA2C
Uniprot ID:
P18825
Molecular Weight:
49521.585 Da
References
  1. Kvernmo T, Houben J, Sylte I: Receptor-binding and pharmacokinetic properties of dopaminergic agonists. Curr Top Med Chem. 2008;8(12):1049-67. [PubMed:18691132 ]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Steroid hydroxylase activity
Specific Function:
Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic antidepressants.
Gene Name:
CYP2D6
Uniprot ID:
P10635
Molecular Weight:
55768.94 Da
References
  1. Kvernmo T, Houben J, Sylte I: Receptor-binding and pharmacokinetic properties of dopaminergic agonists. Curr Top Med Chem. 2008;8(12):1049-67. [PubMed:18691132 ]
  2. 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. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]
Kind
Protein
Organism
Human
Pharmacological action
unknown
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 reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4-hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiot...
Gene Name:
CYP3A4
Uniprot ID:
P08684
Molecular Weight:
57342.67 Da
References
  1. Kvernmo T, Houben J, Sylte I: Receptor-binding and pharmacokinetic properties of dopaminergic agonists. Curr Top Med Chem. 2008;8(12):1049-67. [PubMed:18691132 ]
  2. 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. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]
Comments
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Drug created on June 13, 2005 07:24 / Updated on August 17, 2016 12:23