Bicuculline (CED0002465)

Record Information

Version

1.0

Creation Date

2014-08-29 05:03:00 UTC

Update Date

2026-08-20 05:01:34 UTC

SynCED ID

CED0002465

Secondary Accession Numbers

CHEM003033
T3D4073

Identification

Common Name

Bicuculline

Class

Small Molecule

Description

Bicuculline is an exogenous solid with the formula C20H17NO6 and an average molecular weight of 367.35 g/mol. Bicuculline belongs to the phthalide isoquinolines, a class of alkaloids and derivatives within the organic compounds. It functions biologically as a GABA antagonist, a GABA-gated chloride channel antagonist, and a neurotoxin. Its protein targets include the histamine H1 receptor (HRH1) and the alpha-1, alpha-3, and alpha-6 subunits of the gamma-aminobutyric acid receptor (GABRA1, GABRA3, and GABRA6). In terms of application, the compound is used as a central nervous system stimulant, a GABA antagonist, and an agrochemical. It is found in 15 recorded sources across multiple sectors, including energy, oil & gas (lubricants); industrial manufacturing & chemical processing (lubricants); healthcare, pharmaceuticals & veterinary products (medical devices); food, food processing & cookware (food packaging); textiles, leather & furnishings (synthetic textiles, carpets and rugs); and electrical & electronic equipment (cell phones, capacitors, wires and cables, batteries, and printed circuit boards). Recorded routes of exposure for the compound include oral, inhalation, and touch.

Contaminant Type

Amine
Ester
Human Neurotoxin
Natural Compound
Organic Compound
PFAS
Phytotoxin
Plant Toxin

Chemical Structure

MOL SDF PDB SMILES InChI

Synonyms

Value	Source
Bicculine	ChEBI
Bicucullin	ChEBI
D-Bicuculline	ChEBI
6-(5,6,7,8-tetrahydro-6-Methyl-1,3-dioxolo(4,5-g)isoquinolin-5-yl)furo(3,4-e)1,3-benzodioxol-8(6H)one	MeSH

Chemical Formula

C₂₀H₁₇NO₆

Average Molecular Mass

367.352 g/mol

Monoisotopic Mass

367.106 g/mol

CAS Registry Number

485-49-4

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 Name

bicuculline

SMILES

[H][C@]1(OC(=O)C2=C1C=CC1=C2OCO1)[C@@]1([H])N(C)CCC2=CC3=C(OCO3)C=C12

InChI Identifier

InChI=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 Key

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.

Kingdom

Organic compounds

Super Class

Alkaloids and derivatives

Class

Phthalide isoquinolines

Sub Class

Not Available

Direct Parent

Phthalide 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 Framework

Aromatic heteropolycyclic compounds

External Descriptors

isoquinoline alkaloid (CHEBI:3092 )
isoquinolines (CHEBI:3092 )
Isoquinoline alkaloids (C09364 )

Biological Properties

Status

Detected and Not Quantified

Origin

Exogenous

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 Locations

Not Available

Tissue Locations

Not Available

Applications

Biological Roles

neurotoxin ?A chemical substance that interferes with the normal functioning of the nervous system
GABA antagonist (PMC10177384 )?
GABA-gated chloride channel antagonist ?
antagonist (PMC5862131 , PMC10831359 )?Substance that attaches to and blocks cell receptors that normally bind naturally occurring substances.
GABAA receptor antagonist (PMC5862131 , PMC5862131 )?

Chemical Roles

Not Available

Organoleptic Effects

Not Available

Physical Properties

State

Solid

Appearance

White powder.

Experimental Properties

Property	Value
Melting Point	Not Available
Boiling Point	Not Available
Solubility	Not Available

Predicted Properties

Property	Value	Source
Water Solubility	0.36 g/L	ALOGPS
logP	1.76	ALOGPS
logP	2.68	ChemAxon
logS	-3	ALOGPS
pKa (Strongest Acidic)	14.72	ChemAxon
pKa (Strongest Basic)	7.43	ChemAxon
Physiological Charge	1	ChemAxon
Hydrogen Acceptor Count	6	ChemAxon
Hydrogen Donor Count	0	ChemAxon
Polar Surface Area	66.46 Å²	ChemAxon
Rotatable Bond Count	1	ChemAxon
Refractivity	93.45 m³·mol⁻¹	ChemAxon
Polarizability	37.3 Å³	ChemAxon
Number of Rings	6	ChemAxon
Bioavailability	Yes	ChemAxon
Rule of Five	Yes	ChemAxon
Ghose Filter	Yes	ChemAxon
Veber's Rule	No	ChemAxon
MDDR-like Rule	No	ChemAxon

Spectra

Spectrum Type	Description	Splash Key	Deposition Date	View
LC-MS/MS	LC-MS/MS Spectrum	splash10-056s-2592000000-e3973ba2799d460c3b59	Not Available	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum	splash10-014i-0009000000-7549cdeeb71ef4470dc1	Not Available	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum	splash10-066r-0009000000-d8e744c493912dace636	Not Available	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum	splash10-0a4i-0039000000-01b4f70e0d954ed7658e	Not Available	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum	splash10-004j-0091000000-4bda65b490b53129adf9	Not Available	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum	splash10-0aor-0109000000-40c14a57cb6620310332	Not Available	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum	splash10-0a4i-0309000000-7ca1258f5e6afe7f84cd	Not Available	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum	splash10-01p9-0906000000-4d63889ee99dca8cab11	Not Available	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum	splash10-0a4i-0039000000-b9f59e9657a74348c6a2	Not Available	View Spectrum
LC-MS/MS	LC-MS/MS Spectrum	splash10-056s-2592000000-e3973ba2799d460c3b59	Not Available	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum	splash10-014i-0009000000-c181caec72711cdf90a7	Not Available	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum	splash10-01b9-0309000000-911d653eff0bb92aaf9b	Not Available	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum	splash10-004i-0952000000-1eef2687ebf3adc6ff75	Not Available	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum	splash10-014i-0009000000-6556b5579b30115da7f1	Not Available	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum	splash10-01b9-0019000000-577733de055f298b7dee	Not Available	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum	splash10-00fu-4298000000-9af528a64d0ecefbf9ab	Not Available	View Spectrum

Toxicity Profile

Toxicity Values

Toxicity Value	Organism	Dose Descriptor	Route of Exposure	Predicted or Experimental	Toxicity Rating	Reference
733.0 Log mg/kg [410:1300]	Rat	LD50	oral	predicted	Not Available	Not Available

Toxicity / Toxin Class

Not Available

Mechanism of Toxicity

The 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.

Carcinogenicity (IARC Classification)

No indication of carcinogenicity to humans (not listed by IARC).

Minimum Risk Level

Not Available

Symptoms

Not Available

Treatment

Not Available

Health Effects

Health Effect	Relationship	Direction	Description	Reference

Exposure Sources

Source ID	Source	Sector	Reference
CEDs000007	Pesticides?Pesticides are synthetic chemicals designed to prevent, destroy, or control pests that threaten crops and agricultural productivity.	Agriculture & land management	Not Available
CEDs000120	Wires and cables?Wires and cables are integral components in the transmission of electrical power and signals.	Electrical & Electronic Equipment	Not Available
CEDs000121	Printed circuit boards?Printed circuit boards (PCBs) are essential components in the manufacturing of electronic devices, serving as the backbone for electrical connections and circuit pathways.	Electrical & Electronic Equipment	Not Available
CEDs000125	Batteries?Batteries are devices that store and release electrical energy through electrochemical reactions.	Electrical & Electronic Equipment	Not Available
CEDs000130	Semiconductors?Semiconductors are materials that possess electrical conductivity between that of conductors and insulators, making them essential for various electronic applications, including transistors, diodes, and integrated circuits.	Electrical & Electronic Equipment	Not Available
CEDs000138	Lubricants?Lubricants are synthetic or petroleum-derived substances used to reduce friction between surfaces in machinery and equipment, enhancing operational efficiency and longevity.	Energy, oil & gas	Not Available
CEDs000147	Food packaging?Food packaging often utilizes synthetic chemicals, such as plastics and coatings, to enhance durability, moisture resistance, and shelf life.	Food, food processing & cookware	Not Available
CEDs000174	Lubricants?Lubricants are synthetic or petroleum-based substances used to reduce friction and wear between moving parts in machinery and equipment.	Industrial manufacturing & chemical processing	Not Available
CEDs000234	Medical devices?Medical devices often incorporate synthetic chemicals in their manufacturing processes, which can contribute to contamination in healthcare settings.	Healthcare, pharmaceuticals & veterinary products	Not Available
CEDs000451	Carpets and Rugs?Carpets and rugs are commonly manufactured using synthetic fibers such as nylon, polyester, and polypropylene, which can be derived from petrochemical sources.	Textiles, leather & furnishings	Not Available
CEDs000454	Synthetic textiles?Synthetic textiles are materials derived from man-made fibers, such as polyester, nylon, and acrylic, which are produced through chemical processes involving petrochemicals.	Textiles, leather & furnishings	Not Available
CEDs000490		Personal care & cosmetics	Not Available
CEDs000492	Cell phones?Cell phones contain a variety of synthetic chemicals and materials, including plastics, metals, and glass, which can contribute to environmental contamination.	Electrical & Electronic Equipment	Not Available
CEDs000493	Capacitors?Capacitors are electronic components that store and release electrical energy, often using dielectric materials that can include synthetic chemicals.	Electrical & Electronic Equipment	Not Available
CEDs000511	Conductors Or Conductive Bodies Characterised By The Conductive Materials?Conductors, or conductive bodies, are materials that allow the flow of electrical current, typically made from metals such as copper, aluminum, or silver.	Electrical & Electronic Equipment	PubChem
CEDs000519	Electrodes?Electrodes, used in various electrical and electronic applications, can be a source of synthetic chemical contamination due to the materials from which they are constructed and the processes involved in their manufacturing.	Electrical & Electronic Equipment	PubChem
CEDs000606	Plant Growth Regulators?Plant Growth Regulators (PGRs) are synthetic chemicals designed to influence the growth and development of plants.	Agriculture & land management	PubChem
CEDs000696	Nanotechnology?Nanotechnology involves the manipulation of materials at the molecular or atomic level, typically within the range of 1 to 100 nanometers.	Industrial manufacturing & chemical processing	PubChem

Pathways

14 pathwaysPathway Source: PathBank

Long-term potentiation

Gastric acid secretion

Renin-angiotensin system

Metabolic Pathways

Glycerolipid Metabolism

Gabaergic synapse

View all 14 pathways

Targets

Structure	Protein	UniProt ID	Organism	Relationship	Details
Click to view 3D structure	D(2) dopamine receptor	P14416	Humans	Predicted (SEA)	Prediction Confidence Score 0.362 Applicability Domain 0.418 Statistical Significance 0.0335 Supporting Reference Compounds 1103 E-value 260.873
Click to view 3D structure	Alpha-1A adrenergic receptor	P35348	Humans	Predicted (SEA)	Prediction Confidence Score 0.354 Applicability Domain 0.443 Statistical Significance 0.0138 Supporting Reference Compounds 376 E-value 107.354
Click to view 3D structure	D(1A) dopamine receptor	P21728	Humans	Predicted (SEA)	Prediction Confidence Score 0.348 Applicability Domain 0.356 Statistical Significance 0.0148 Supporting Reference Compounds 425 E-value 114.905
Click to view 3D structure	D(2) dopamine receptor	P61169	Rat	Predicted (SEA)	Prediction Confidence Score 0.345 Applicability Domain 0.443 Statistical Significance 0.0266 Supporting Reference Compounds 528 E-value 207.001
Click to view 3D structure	D(1A) dopamine receptor	P18901	Rattus norvegicus	Predicted (SEA)	Prediction Confidence Score 0.336 Applicability Domain 0.443 Statistical Significance 0.0126 Supporting Reference Compounds 206 E-value 98.4793
Click to view 3D structure	5-hydroxytryptamine receptor 1A	P08908	Humans	Predicted (SEA)	Prediction Confidence Score 0.33 Applicability Domain 0.353 Statistical Significance 0.0426 Supporting Reference Compounds 953 E-value 331.404
Click to view 3D structure	Zinc finger protein mex-5	Q9XUB2	Caenorhabditis elegans	Predicted (SEA)	Prediction Confidence Score 0.329 Applicability Domain 0.476 Statistical Significance 5.70e-04 Supporting Reference Compounds 88 E-value 4.43741
Click to view 3D structure	Alpha-1D adrenergic receptor	P25100	Humans	Predicted (SEA)	Prediction Confidence Score 0.326 Applicability Domain 0.443 Statistical Significance 0.014 Supporting Reference Compounds 258 E-value 108.833
Click to view 3D structure	Tissue factor	P13726	Humans	Predicted (SEA)	Prediction Confidence Score 0.323 Applicability Domain 0.356 Statistical Significance 0.003 Supporting Reference Compounds 29 E-value 23.1212
Click to view 3D structure	5-hydroxytryptamine receptor 1A	P19327	Rattus norvegicus	Predicted (SEA)	Prediction Confidence Score 0.321 Applicability Domain 0.333 Statistical Significance 0.0357 Supporting Reference Compounds 541 E-value 278.311
Click to view 3D structure	5-hydroxytryptamine receptor 7	P32305	Rattus norvegicus	Predicted (SEA)	Prediction Confidence Score 0.321 Applicability Domain 0.333 Statistical Significance 0.0116 Supporting Reference Compounds 115 E-value 90.6943
Click to view 3D structure	D(3) dopamine receptor	P35462	Humans	Predicted (SEA)	Prediction Confidence Score 0.317 Applicability Domain 0.353 Statistical Significance 0.0506 Supporting Reference Compounds 861 E-value 393.606
Click to view 3D structure	X-box-binding protein 1	Q9R1S4	Rattus norvegicus	Predicted (SEA)	Prediction Confidence Score 0.315 Applicability Domain 0.315 Statistical Significance 5.00e-05 Supporting Reference Compounds 1 E-value 0.389246
Click to view 3D structure	5-hydroxytryptamine receptor 7	P34969	Humans	Predicted (SEA)	Prediction Confidence Score 0.309 Applicability Domain 0.333 Statistical Significance 0.0415 Supporting Reference Compounds 565 E-value 322.919
Click to view 3D structure	D(4) dopamine receptor	P21917	Humans	Predicted (SEA)	Prediction Confidence Score 0.307 Applicability Domain 0.353 Statistical Significance 0.0489 Supporting Reference Compounds 524 E-value 380.527
Click to view 3D structure	Alpha-1B adrenergic receptor	P35368	Humans	Predicted (SEA)	Prediction Confidence Score 0.305 Applicability Domain 0.443 Statistical Significance 0.0251 Supporting Reference Compounds 298 E-value 195.402
Click to view 3D structure	5-hydroxytryptamine receptor 2A	P28223	Humans	Predicted (SEA)	Prediction Confidence Score 0.305 Applicability Domain 0.333 Statistical Significance 0.0731 Supporting Reference Compounds 955 E-value 568.922
Click to view 3D structure	D(1B) dopamine receptor	P21918	Humans	Predicted (SEA)	Prediction Confidence Score 0.304 Applicability Domain 0.353 Statistical Significance 0.0207 Supporting Reference Compounds 209 E-value 161.148
Click to view 3D structure	Sodium-dependent serotonin transporter	P31652	Rattus norvegicus	Predicted (SEA)	Prediction Confidence Score 0.303 Applicability Domain 0.323 Statistical Significance 0.0288 Supporting Reference Compounds 297 E-value 224.595
Click to view 3D structure	5-hydroxytryptamine receptor 2B	P41595	Humans	Predicted (SEA)	Prediction Confidence Score 0.3 Applicability Domain 0.333 Statistical Significance 0.0534 Supporting Reference Compounds 686 E-value 416.104
Click to view 3D structure	Alpha-2A adrenergic receptor	P08913	Humans	Predicted (SEA)	Prediction Confidence Score 0.299 Applicability Domain 0.333 Statistical Significance 0.0426 Supporting Reference Compounds 487 E-value 331.793
Click to view 3D structure	Alpha-2B adrenergic receptor	P18089	Humans	Predicted (SEA)	Prediction Confidence Score 0.297 Applicability Domain 0.333 Statistical Significance 0.0298 Supporting Reference Compounds 340 E-value 232.224
Click to view 3D structure	Alpha-2C adrenergic receptor	P18825	Humans	Predicted (SEA)	Prediction Confidence Score 0.297 Applicability Domain 0.333 Statistical Significance 0.0334 Supporting Reference Compounds 386 E-value 260.172
Click to view 3D structure	Cholinesterase	P81908	Equus caballus	Predicted (SEA)	Prediction Confidence Score 0.294 Applicability Domain 0.443 Statistical Significance 0.0292 Supporting Reference Compounds 201 E-value 227.164
Click to view 3D structure	Cytochrome P450 2C9	P11712	Humans	Predicted (SEA)	Prediction Confidence Score 0.293 Applicability Domain 0.578 Statistical Significance 0.1611 Supporting Reference Compounds 1245 E-value 1254.0
Click to view 3D structure	Gamma-aminobutyric acid receptor subunit alpha-1	P14867	Humans	Known	Not Available
Click to view 3D structure	Gamma-aminobutyric acid receptor subunit alpha-3	P34903	Humans	Known	Not Available
Click to view 3D structure	Gamma-aminobutyric acid receptor subunit alpha-6	Q16445	Humans	Known	Not Available
Click to view 3D structure	Histamine H1 receptor	P35367	Humans	Known	Not Available