Bicuculline is a

phthalide Phthalide is an organic chemical compound with the molecular formula C8H6O2. A white solid, it is the simplest benzo lactone. It is prepared from hydroxymethylbenzoic acid. Phthalides The phthalide core is found a variety of more complex chemic ...

-isoquinoline compound that is a light-sensitive competitive

antagonist An antagonist is a character in a story who is presented as the chief foe of the protagonist. Etymology The English word antagonist comes from the Greek ἀνταγωνιστής – ''antagonistēs'', "opponent, competitor, villain, enemy, riv ...

of GABA_A receptors. It was originally identified in 1932 in plant

alkaloid Alkaloids are a class of basic, naturally occurring organic compounds that contain at least one nitrogen atom. This group also includes some related compounds with neutral and even weakly acidic properties. Some synthetic compounds of similar ...

extracts and has been isolated from ''

Dicentra cucullaria ''Dicentra cucullaria'', Dutchman's britches, or Dutchman's breeches, is a perennial herbaceous plant, native to rich woods of eastern North America, with a disjunct population in the Columbia Basin. The common name Dutchman's breeches derives ...

'', '' Adlumia fungosa'', and several ''

Corydalis ''Corydalis'' (from Greek ''korydalís'' "crested lark") is a genus of about 470 species of annual and perennial herbaceous plants in the family Papaveraceae, native to the temperate Northern Hemisphere and the high mountains of tropical eastern ...

'' species (all in

subfamily In biological classification, a subfamily (Latin: ', plural ') is an auxiliary (intermediate) taxonomic rank, next below family but more inclusive than genus. Standard nomenclature rules end subfamily botanical names with "-oideae", and zoologi ...

Fumarioideae Fumarioideae is a subfamily of the family Papaveraceae (the poppy family). It was formerly treated as a separate family, the Fumariaceae (the fumitory, fumewort or bleeding-heart family). It consists of about 575 species of herbaceous plants in 20 ...

, previously known as

family Family (from la, familia) is a Social group, group of people related either by consanguinity (by recognized birth) or Affinity (law), affinity (by marriage or other relationship). The purpose of the family is to maintain the well-being of its ...

Fumariaceae). Since it blocks the inhibitory action of GABA receptors, the action of bicuculline mimics

epilepsy Epilepsy is a group of non-communicable neurological disorders characterized by recurrent epileptic seizures. Epileptic seizures can vary from brief and nearly undetectable periods to long periods of vigorous shaking due to abnormal electrical ...

; it also causes

convulsion A convulsion is a medical condition where the body muscles contract and relax rapidly and repeatedly, resulting in uncontrolled shaking. Because epileptic seizures typically include convulsions, the term ''convulsion'' is sometimes used as a s ...

s. This property is utilized in laboratories around the world in the ''in vitro'' study of epilepsy, generally in

hippocampal The hippocampus (via Latin from Greek , 'seahorse') is a major component of the brain of humans and other vertebrates. Humans and other mammals have two hippocampi, one in each side of the brain. The hippocampus is part of the limbic system, an ...

or cortical neurons in prepared brain slices from rodents. This compound is also routinely used to isolate

glutamatergic Glutamatergic means "related to glutamate". A glutamatergic agent (or drug) is a chemical that directly modulates the excitatory amino acid (glutamate/ aspartate) system in the body or brain. Examples include excitatory amino acid receptor agonist ...

(excitatory amino acid) receptor function. The action of bicuculline is primarily on the

ionotropic Ligand-gated ion channels (LICs, LGIC), also commonly referred to as ionotropic receptors, are a group of transmembrane ion-channel proteins which open to allow ions such as Na+, K+, Ca2+, and/or Cl− to pass through the membrane in res ...

GABA_A receptors, which are ligand-gated

ion An ion () is an atom or molecule with a net electrical charge. The charge of an electron is considered to be negative by convention and this charge is equal and opposite to the charge of a proton, which is considered to be positive by conve ...

channels concerned chiefly with the passing of chloride ions across the cell membrane, thus promoting an inhibitory influence on the target

neuron A neuron, neurone, or nerve cell is an electrically excitable cell that communicates with other cells via specialized connections called synapses. The neuron is the main component of nervous tissue in all animals except sponges and placozoa. N ...

. These receptors are the major targets for

benzodiazepines Benzodiazepines (BZD, BDZ, BZs), sometimes called "benzos", are a class of depressant drugs whose core chemical structure is the fusion of a benzene ring and a diazepine ring. They are prescribed to treat conditions such as anxiety disorders, i ...

and related

anxiolytic An anxiolytic (; also antipanic or antianxiety agent) is a medication or other intervention that reduces anxiety. This effect is in contrast to anxiogenic agents which increase anxiety. Anxiolytic medications are used for the treatment of anxi ...

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. Sensitivity to bicuculline is defined by

IUPHAR The International Union of Basic and Clinical Pharmacology (IUPHAR) is a voluntary, non-profit association representing the interests of scientists in pharmacology-related fields to facilitate ''Better Medicines through Global Education and Resear ...

as a major criterion in the definition of GABA_A receptors

References

{{Glycinergics GABAA receptor antagonists Glycine receptor antagonists Convulsants 3-(5,6,7,8-tetrahydro-(1,3)dioxolo(4,5-g)isoquinolin-5-yl)-3H-2-benzofuran-1-ones Benzylisoquinoline alkaloids

See also

References