Bicuculline

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IUPAC_name = Bicuculline

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CAS_number = 485-49-4
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PubChem = 10237
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smiles = C1=C6C(=CC2=C1CCN( [C@@H] 2 [C@H] 3C4C(C(O3)=O)C5=C(C=C4)OCO5)C)OCO6
C=20 | H=17 | N=1 | O=6
molecular_weight = 367.352 g/mol
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Bicuculline (BIC) is a light-sensitive competitive antagonist of GABA_A receptors. It was originally identified in 1932 in plant alkaloid extracts [Manske, Can. J. Res. 7:265, 1932] 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 utilised 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 (IC50) effect of bicuculline on GABA_A receptors is 3 μM.

In addition to being a potent GABA_A receptor antagonist, bicuculine can be used to block Ca²⁺-activated potassium channels [Khawaled R, Bruening-Wright A, Adelman JP, Maylie J (1999) Bicuculline block of small-conductance calcium-activated potassium channels. Pflügers Arch 438: 314-321] .

Sensitivity to bicuculline is defined by IUPHAR as a major criterion in the definition of GABA_A receptors — however in recent years a new class of ionotropic GABA receptor, defined variously as GABA_A or GABA_C has been characterised, which is insensitive to both benzodiazepines and bicuculline.

A water soluble form of bicuculline, bicuculline methiodide, is soluble in water to a concentration of 10 mg/mL.

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