Bicuculline

Bicuculline

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
Identifiers
CAS Number	485-49-4
ATC code	none
PubChem	CID 10237
IUPHAR/BPS	2312
ChemSpider	9820
UNII	Y37615DVKC
ChEBI	CHEBI:3092
ChEMBL	CHEMBL417990
Chemical data
Formula	C20H17NO6
Molar mass	367.352 g/mol
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 Key:IYGYMKDQCDOMRE-ZWKOTPCHSA-N
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Bicuculline is a light-sensitive competitive antagonist of GABA_A 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 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 and related anxiolytic drugs.

The half-maximal inhibitory concentration (IC₅₀) of bicuculline on GABA_A receptors is 3 μM.

In addition to being a potent GABA_A 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 GABA_A receptors 

See also

• Picrotoxin

References

1. Manske, R. H. F. (1932). "The Alkaloids of Fumaraceous Plants. II. Dicentra cucullaria (L.) Bernh.". Canadian Journal of Research 7: 265–269. doi:10.1139/cjr32-078.
2. Khawaled, R.; Bruening-Wright, A.; Adelman, J. P.; Maylie, J. (1999). "Bicuculline Block of Small-conductance Calcium-activated Potassium Channels". Pflügers Archiv : European Journal of Physiology 438 (3): 314–321. doi:10.1007/s004240050915. ISSN 0031-6768. PMID 10398861.