Bicuculline

Title: Bicuculline
CAS Registry Number: 485-49-4
CAS Name: (6R)-6-[(5S)-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
Molecular Formula: C20H17NO6
Molecular Weight: 367.35
Percent Composition: C 65.39%, H 4.66%, N 3.81%, O 26.13%
Literature References: Alkaloid naturally occurring in the d-form; found in Dicentra cucullaria (L.) Bernh., Adlumia fungosa (Ait.) Greene, Fumariaceae, and several Corydalis species: Manske, Can. J. Res. 7, 265 (1932); 8, 210, 407 (1933); 9, 436 (1933); Edwards, Handa, Can. J. Chem. 39, 1801 (1961). Synthesis of dl-form: Groenewoud, Robinson, J. Chem. Soc. 1936, 199. Resolution of isomers: Haworth et al., Nature 165, 529 (1950). Stereoisomer of adlumidine, q.v., and of capnoidine: Manske, J. Am. Chem. Soc. 72, 3207 (1950). Preliminary stereochemical studies: Safe, Moir, Can. J. Chem. 42, 160 (1964). Revised stereochemistry: Blaha et al., Collect. Czech. Chem. Commun. 29, 2328 (1964); Snatzke et al., Tetrahedron 25, 5059 (1969). Crystal and molecular structure: Gorinsky, Moss, J. Cryst. Mol. Struct. 3, 299 (1973). Shows GABA (q.v.) antagonist activity: Curtis et al., Nature 226, 1222 (1970).
Properties: Elongated plates from chloroform-methanol, mp 215°; also reported as mp 177°, solidifies and remelts 193-195°: Manske, Can. J. Res. 21B, 13 (1943). uv max (acidified ethanol): 225, 296, 324 nm (e 36700, 6390, 5870). [a]D25 +130.5° (CHCl3). pKa 4.84. Sol in benzene, chloroform, ethyl acetate. Sparingly sol in alc and ether.
Melting point: mp 215°; mp 177°
pKa: pKa 4.84
Optical Rotation: [a]D25 +130.5° (CHCl3)
Absorption maximum: uv max (acidified ethanol): 225, 296, 324 nm (e 36700, 6390, 5870)
Bidisomide Bietamiverine Bietanautine Bietaserpine Bifemelane

Bicuculline
Bicuculline.svg
Systematic (IUPAC) name
(6R)-​6-​[(5S)-​6-​methyl-​5,​6,​7,​8-​tetrahydro​[1,3]dioxolo​[4,5-g]​isoquinolin-​5-​yl]​furo[3,4-e]​[1,3]​benzodioxol-​8(6H)-​one
Clinical data
Legal status  ?
Identifiers
CAS number 485-49-4 YesY
ATC code None
PubChem CID 10237
IUPHAR ligand 2312
ChemSpider 9820 YesY
UNII Y37615DVKC N
ChEBI CHEBI:3092 N
ChEMBL CHEMBL417990 N
Chemical data
Formula C20H17NO6 
Mol. mass 367.352 g/mol
 N (what is this?)  (verify)

Bicuculline is a light-sensitive competitive antagonist of GABAA receptors. It was originally identified in 1932 in plant alkaloid extracts[1] 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.

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.[2]

Sensitivity to bicuculline is defined by IUPHAR as a major criterion in the definition of GABAA receptors