Bicuculline
Encyclopedia
Bicuculline is a light-sensitive competitive antagonist
of GABAA
receptors. It was originally identified in 1932 in plant alkaloid extracts 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.
Bicuculline is also a pharmcological agent that, when used, increases the frequency of occurrence of ocular saccades during visual fixation.
The action of bicuculline is primarily on the ionotropic GABAA
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 GABAA receptors is 3 μM.
In addition to being a potent GABAA receptor antagonist, bicuculine can be used to block Ca2+-activated potassium channels.
Sensitivity to bicuculline is defined by IUPHAR as a major criterion in the definition of GABAA receptors
A water soluble form of bicuculline, bicuculline methiodide (BMI), is soluble in water to a concentration of 10 mg/mL.
Receptor antagonist
A receptor antagonist is a type of receptor ligand or drug that does not provoke a biological response itself upon binding to a receptor, but blocks or dampens agonist-mediated responses...
of GABAA
GABA A receptor
The GABAA receptor is an ionotropic receptor and ligand-gated ion channel. Its endogenous ligand is γ-aminobutyric acid , the major inhibitory neurotransmitter in the central nervous system. Upon activation, the GABAA receptor selectively conducts Cl- through its pore, resulting in...
receptors. It was originally identified in 1932 in plant alkaloid extracts 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
Epilepsy
Epilepsy is a common chronic neurological disorder characterized by seizures. These seizures are transient signs and/or symptoms of abnormal, excessive or hypersynchronous neuronal activity in the brain.About 50 million people worldwide have epilepsy, and nearly two out of every three new cases...
. This property is utilized in laboratories across the world in the in vitro study of epilepsy, generally in hippocampal
Hippocampus
The hippocampus is a major component of the brains of humans and other vertebrates. It belongs to the limbic system and plays important roles in the consolidation of information from short-term memory to long-term memory and spatial navigation. Humans and other mammals have two hippocampi, one in...
or cortical
Cerebral cortex
The cerebral cortex is a sheet of neural tissue that is outermost to the cerebrum of the mammalian brain. It plays a key role in memory, attention, perceptual awareness, thought, language, and consciousness. It is constituted of up to six horizontal layers, each of which has a different...
neurons in prepared brain slices from rodents. This compound is also routinely used to isolate glutamatergic (excitatory amino acid) receptor function.
Bicuculline is also a pharmcological agent that, when used, increases the frequency of occurrence of ocular saccades during visual fixation.
The action of bicuculline is primarily on the ionotropic GABAA
GABA A receptor
The GABAA receptor is an ionotropic receptor and ligand-gated ion channel. Its endogenous ligand is γ-aminobutyric acid , the major inhibitory neurotransmitter in the central nervous system. Upon activation, the GABAA receptor selectively conducts Cl- through its pore, resulting in...
receptors, which are ligand-gated ion
Ion
An ion is an atom or molecule in which the total number of electrons is not equal to the total number of protons, giving it a net positive or negative electrical charge. The name was given by physicist Michael Faraday for the substances that allow a current to pass between electrodes in a...
channels concerned chiefly with the passing of chloride ions across the cell membrane, thus promoting an inhibitory influence on the target neuron
Neuron
A neuron is an electrically excitable cell that processes and transmits information by electrical and chemical signaling. Chemical signaling occurs via synapses, specialized connections with other cells. Neurons connect to each other to form networks. Neurons are the core components of the nervous...
. These receptors are the major targets for benzodiazepines and related anxiolytic
Anxiolytic
An anxiolytic is a drug used for the treatment of anxiety, and its related psychological and physical symptoms...
drugs.
The half-maximal inhibitory concentration (IC50
IC50
The half maximal inhibitory concentration is a measure of the effectiveness of a compound in inhibiting biological or biochemical function. This quantitative measure indicates how much of a particular drug or other substance is needed to inhibit a given biological process by half...
) of bicuculline on GABAA receptors is 3 μM.
In addition to being a potent GABAA receptor antagonist, bicuculine can be used to block Ca2+-activated potassium channels.
Sensitivity to bicuculline is defined by IUPHAR as a major criterion in the definition of GABAA receptors
A water soluble form of bicuculline, bicuculline methiodide (BMI), is soluble in water to a concentration of 10 mg/mL.