Bicuculline

Bicuculline is a phthalide-isoquinoline compound that is a light-sensitive competitive antagonist of GABA_A receptors.^[1] It was originally identified in 1932 in plant alkaloid extracts^[2] and has been isolated from Dicentra cucullaria, Adlumia fungosa, and several Corydalis species (all in subfamily Fumarioideae, previously known as family Fumariaceae). Since it blocks the inhibitory action of GABA receptors, the action of bicuculline mimics epilepsy; it also causes convulsions. This property is utilized in laboratories around 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.

Bicuculline

Clinical data
ATC code	none
Identifiers
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
CAS Number	485-49-4 Y
PubChem CID	10237
IUPHAR/BPS	2312
ChemSpider	9820 Y
UNII	Y37615DVKC
ChEBI	CHEBI:3092 N
ChEMBL	ChEMBL417990 N
PDB ligand	H0Z (PDBe, RCSB PDB)
CompTox Dashboard (EPA)	DTXSID3042687
ECHA InfoCard	100.006.927
Chemical and physical data
Formula	C20H17NO6
Molar mass	367.357 g·mol−1
3D model (JSmol)	Interactive image
Melting point	215 °C (419 °F)
SMILES O=C1O[C@H](c3c1c2OCOc2cc3)[C@@H]5c4cc6OCOc6cc4CCN5C
InChI 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 Y Key:IYGYMKDQCDOMRE-ZWKOTPCHSA-N Y
NY (what is this?)  (verify)

The action of bicuculline is primarily on the ionotropic GABA_A 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, z-drugs, and related anxiolytic drugs.

The half-maximal inhibitory concentration (IC₅₀) of bicuculline on GABA_A receptors is 3 μM.^{[citation needed]}

In addition to being a potent GABA_A receptor antagonist, bicuculline can be used to block Ca²⁺-activated potassium channels.^[3]

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

See also

• Picrotoxin
• Hydrastine (very similar in structure)