Tmic
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Record Information
Version2.0
Creation Date2014-08-29 05:03:00 UTC
Update Date2014-12-24 20:26:37 UTC
Accession NumberT3D4073
Identification
Common NameBicuculline
ClassSmall Molecule
DescriptionBicuculline is a light-sensitive competitive antagonist of GABAA receptors. It was originally identified in 1932 in plant alkaloid extracts and has been isolated from Dicentra cucullaria, Adlumia fungosa, Fumariaceae, and several Corydalis species. Since it blocks the inhibitory action of GABA receptors, the action of bicuculline mimics epilepsy. This property is utilized in laboratories across the world in the in vitro study of epilepsy, generally in hippocampal or cortical neurons in prepared brain slices from rodents. This compound is also routinely used to isolate glutamatergic (excitatory amino acid) receptor function.
Compound Type
  • Amine
  • Ester
  • Natural Compound
  • Organic Compound
  • Plant Toxin
Chemical Structure
Thumb
Synonyms
Synonym
Bicculine
Bicucullin
D-Bicuculline
Chemical FormulaC20H17NO6
Average Molecular Mass367.352 g/mol
Monoisotopic Mass367.106 g/mol
CAS Registry Number485-49-4
IUPAC Name(10R)-10-[(5S)-6-methyl-2H,5H,6H,7H,8H-[1,3]dioxolo[4,5-g]isoquinolin-5-yl]-3,5,11-trioxatricyclo[7.3.0.0²,⁶]dodeca-1(9),2(6),7-trien-12-one
Traditional Namebicuculline
SMILES[H][C@]1(OC(=O)C2=C1C=CC1=C2OCO1)[C@@]1([H])N(C)CCC2=CC3=C(OCO3)C=C12
InChI IdentifierInChI=1S/C20H17NO6/c1-21-5-4-10-6-14-15(25-8-24-14)7-12(10)17(21)18-11-2-3-13-19(26-9-23-13)16(11)20(22)27-18/h2-3,6-7,17-18H,4-5,8-9H2,1H3/t17-,18+/m0/s1
InChI KeyInChIKey=IYGYMKDQCDOMRE-ZWKOTPCHSA-N
Chemical Taxonomy
Description belongs to the class of organic compounds known as phthalide isoquinolines. These are organic compounds with a structure characterized by an isoquinoline moiety linked to phthalide.
KingdomOrganic compounds
Super ClassAlkaloids and derivatives
ClassPhthalide isoquinolines
Sub ClassNot Available
Direct ParentPhthalide isoquinolines
Alternative Parents
Substituents
  • Phthalide isoquinoline
  • Benzofuranone
  • Phthalide
  • Isobenzofuranone
  • Tetrahydroisoquinoline
  • Benzodioxole
  • Isocoumaran
  • Aralkylamine
  • Benzenoid
  • Amino acid or derivatives
  • Carboxylic acid ester
  • Lactone
  • Tertiary amine
  • Tertiary aliphatic amine
  • Monocarboxylic acid or derivatives
  • Acetal
  • Carboxylic acid derivative
  • Oxacycle
  • Organoheterocyclic compound
  • Azacycle
  • Organic oxide
  • Organopnictogen compound
  • Organooxygen compound
  • Organonitrogen compound
  • Amine
  • Organic oxygen compound
  • Hydrocarbon derivative
  • Organic nitrogen compound
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors
Biological Properties
StatusDetected and Not Quantified
OriginExogenous
Cellular Locations
  • Cell junction
  • Cell surface
  • Cytoskeleton
  • Endoplasmic reticulum
  • Extracellular
  • Golgi apparatus
  • Lysosome
  • Membrane
  • Membrane Fraction
  • Mitochondrion
  • Nerve Fiber
  • Nuclear Membrane
  • Plasma Membrane
  • Synaptic Vesicle
Biofluid LocationsNot Available
Tissue LocationsNot Available
Pathways
NameSMPDB LinkKEGG Link
Long-term potentiationNot Availablemap04720
Gastric acid secretionNot Availablemap04971
ProteasomeNot AvailableNot Available
AnticonvulsantsNot AvailableNot Available
Long-term depressionNot Availablemap04730
Circadian rhythmNot Availablemap04710
Opioid AnalgesicsNot AvailableNot Available
EicosanoidsNot AvailableNot Available
Renin-angiotensin systemNot Availablemap04614
Metabolic PathwaysNot AvailableNot Available
Glycerolipid MetabolismSMP00039 map00561
Gabaergic synapseNot Availablemap04727
ApoptosisNot Availablemap04210
AnxiolyticsNot AvailableNot Available
Applications
Biological Roles
Chemical RolesNot Available
Physical Properties
StateSolid
AppearanceWhite powder.
Experimental Properties
PropertyValue
Melting PointNot Available
Boiling PointNot Available
SolubilityNot Available
LogPNot Available
Predicted Properties
PropertyValueSource
Water Solubility0.36 g/LALOGPS
logP1.76ALOGPS
logP2.68ChemAxon
logS-3ALOGPS
pKa (Strongest Acidic)14.72ChemAxon
pKa (Strongest Basic)7.43ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count6ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area66.46 ŲChemAxon
Rotatable Bond Count1ChemAxon
Refractivity93.45 m³·mol⁻¹ChemAxon
Polarizability37.3 ųChemAxon
Number of Rings6ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Spectra
Spectrum TypeDescriptionSplash Key
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-qTof , Positivesplash10-056s-2592000000-e3973ba2799d460c3b59View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-014i-0009000000-7549cdeeb71ef4470dc1View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-066r-0009000000-d8e744c493912dace636View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-0a4i-0039000000-01b4f70e0d954ed7658eView in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-QTOF , positivesplash10-004j-0091000000-4bda65b490b53129adf9View in MoNA
LC-MS/MSLC-MS/MS Spectrum - LC-ESI-ITFT , positivesplash10-0aor-0109000000-40c14a57cb6620310332View in MoNA
LC-MS/MSLC-MS/MS Spectrum - Linear Ion Trap , positivesplash10-0a4i-0309000000-7ca1258f5e6afe7f84cdView in MoNA
LC-MS/MSLC-MS/MS Spectrum - Linear Ion Trap , positivesplash10-01p9-0906000000-4d63889ee99dca8cab11View in MoNA
LC-MS/MSLC-MS/MS Spectrum - Linear Ion Trap , positivesplash10-0a4i-0039000000-b9f59e9657a74348c6a2View in MoNA
LC-MS/MSLC-MS/MS Spectrum - , positivesplash10-056s-2592000000-e3973ba2799d460c3b59View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-014i-0009000000-c181caec72711cdf90a7View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-01b9-0309000000-911d653eff0bb92aaf9bView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-004i-0952000000-1eef2687ebf3adc6ff75View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-014i-0009000000-6556b5579b30115da7f1View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-01b9-0019000000-577733de055f298b7deeView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-00fu-4298000000-9af528a64d0ecefbf9abView in MoNA
1D NMR1H NMR SpectrumNot AvailableView in JSpectraViewer
1D NMR13C NMR SpectrumNot AvailableView in JSpectraViewer
Toxicity Profile
Route of ExposureNot Available
Mechanism of ToxicityThe action of bicuculline is primarily on the ionotropic GABAA receptors, which are ligand-gated ion channels concerned chiefly with the passing of chloride ions across the cell membrane, thus promoting an inhibitory influence on the target neuron. These receptors are the major targets for benzodiazepines and related anxiolytic drugs. The half-maximal inhibitory concentration (IC50) of bicuculline on GABAA receptors is 3 μM. In addition to being a potent GABAA receptor antagonist, bicuculline can be used to block Ca2+-activated potassium channels. Sensitivity to bicuculline is defined by IUPHAR as a major criterion in the definition of GABAA receptors.
MetabolismNot Available
Toxicity ValuesNot Available
Lethal DoseNot Available
Carcinogenicity (IARC Classification)No indication of carcinogenicity to humans (not listed by IARC).
Uses/SourcesIt was originally identified in 1932 in plant alkaloid extracts and has been isolated from Dicentra cucullaria, Adlumia fungosa, Fumariaceae, and several Corydalis species. This compound is also routinely used to isolate glutamatergic (excitatory amino acid) receptor function.
Minimum Risk LevelNot Available
Health EffectsNot Available
SymptomsNot Available
TreatmentNot Available
Normal Concentrations
Not Available
Abnormal Concentrations
Not Available
DrugBank IDNot Available
HMDB IDNot Available
PubChem Compound ID10237
ChEMBL IDCHEMBL417990
ChemSpider ID9820
KEGG IDC09364
UniProt IDNot Available
OMIM ID
ChEBI IDCHEBI:3092
BioCyc IDNot Available
CTD IDNot Available
Stitch IDNot Available
PDB IDNot Available
ACToR IDNot Available
Wikipedia LinkNot Available
References
Synthesis ReferenceNot Available
MSDST3D4073.pdf
General ReferencesNot Available
Gene Regulation
Up-Regulated GenesNot Available
Down-Regulated GenesNot Available

Targets

General Function:
Inhibitory extracellular ligand-gated ion channel activity
Specific Function:
Component of the heteropentameric receptor for GABA, the major inhibitory neurotransmitter in the vertebrate brain. Functions also as histamine receptor and mediates cellular responses to histamine. Functions as receptor for diazepines and various anesthetics, such as pentobarbital; these are bound at a separate allosteric effector binding site. Functions as ligand-gated chloride channel (By similarity).
Gene Name:
GABRA1
Uniprot ID:
P14867
Molecular Weight:
51801.395 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory4.57088 uMNot AvailableBindingDB 50000693
Inhibitory>10 uMNot AvailableBindingDB 50000693
References
  1. Ebert B, Thompson SA, Saounatsou K, McKernan R, Krogsgaard-Larsen P, Wafford KA: Differences in agonist/antagonist binding affinity and receptor transduction using recombinant human gamma-aminobutyric acid type A receptors. Mol Pharmacol. 1997 Dec;52(6):1150-6. [9396785 ]
General Function:
Inhibitory extracellular ligand-gated ion channel activity
Specific Function:
GABA, the major inhibitory neurotransmitter in the vertebrate brain, mediates neuronal inhibition by binding to the GABA/benzodiazepine receptor and opening an integral chloride channel.
Gene Name:
GABRA3
Uniprot ID:
P34903
Molecular Weight:
55164.055 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory2.81838 uMNot AvailableBindingDB 50000693
References
  1. Ebert B, Thompson SA, Saounatsou K, McKernan R, Krogsgaard-Larsen P, Wafford KA: Differences in agonist/antagonist binding affinity and receptor transduction using recombinant human gamma-aminobutyric acid type A receptors. Mol Pharmacol. 1997 Dec;52(6):1150-6. [9396785 ]
General Function:
Inhibitory extracellular ligand-gated ion channel activity
Specific Function:
GABA, the major inhibitory neurotransmitter in the vertebrate brain, mediates neuronal inhibition by binding to the GABA/benzodiazepine receptor and opening an integral chloride channel.
Gene Name:
GABRA6
Uniprot ID:
Q16445
Molecular Weight:
51023.69 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory>10 uMNot AvailableBindingDB 50000693
References
  1. Ebert B, Thompson SA, Saounatsou K, McKernan R, Krogsgaard-Larsen P, Wafford KA: Differences in agonist/antagonist binding affinity and receptor transduction using recombinant human gamma-aminobutyric acid type A receptors. Mol Pharmacol. 1997 Dec;52(6):1150-6. [9396785 ]
General Function:
Histamine receptor activity
Specific Function:
In peripheral tissues, the H1 subclass of histamine receptors mediates the contraction of smooth muscles, increase in capillary permeability due to contraction of terminal venules, and catecholamine release from adrenal medulla, as well as mediating neurotransmission in the central nervous system.
Gene Name:
HRH1
Uniprot ID:
P35367
Molecular Weight:
55783.61 Da
Binding/Activity Constants
TypeValueAssay TypeAssay Source
Inhibitory>10 uMNot AvailableBindingDB 50000693
References
  1. Kanba S, Richelson E: Histamine H1 receptors in human brain labelled with [3H]doxepin. Brain Res. 1984 Jun 18;304(1):1-7. [6146381 ]