First identified in 1932 in plant alkaloid extracts from Dicentra cucullaria (Dutchman's breeches), Adlumia fungosa, and Corydalis species, bicuculline is a light-sensitive phthalide-isoquinoline alkaloid.
Bicuculline competitively blocks the orthosteric GABA binding site on ionotropic GABAA receptors, preventing GABA-gated chloride (Cl⁻) influx and disinhibiting neuronal circuits to provoke epileptiform bursting.
In brain-slice patch-clamp electrophysiology, bath application of bicuculline (typically as its water-soluble methiodide or methobromide salt) silences fast GABAergic inhibitory postsynaptic currents (IPSCs) so excitatory glutamatergic transmission can be studied in isolation.