BICUCULLINE

Investigational

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C20H17NO6
Molecular Weight	367.3521
Optical Activity	UNSPECIFIED
Defined Stereocenters	2 / 2
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CN1CCC2=CC3=C(OCO3)C=C2[C@H]1[C@@H]4OC(=O)C5=C6OCOC6=CC=C45

InChI

InChIKey=IYGYMKDQCDOMRE-ZWKOTPCHSA-N

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

HIDE SMILES / InChI

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/23425285
Curator's Comment: description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/15369839 | https://www.ncbi.nlm.nih.gov/pubmed/27780724 | https://www.ncbi.nlm.nih.gov/pubmed/27520081

Bicuculline is a phthalide-isoquinoline compound that 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.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
GABA-A receptor; anion channel 203 Target ID: CHEMBL2093872 Sources: https://www.ncbi.nlm.nih.gov/pubmed/1331456	Antagonist 2849		44.0 µM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Unknown 2596

PubMed

Title	Date	PubMed
Early onset of glutamatergic and GABAergic synaptic activity in the visual layers of the rodent superior colliculus.	2001-06	11337194
Real-time multisite observation of glutamate release in rat hippocampal slices.	2001-05-18	11335067
Zn2+ differentially modulates signals from red- and short wavelength-sensitive cones to horizontal cells in carp retina.	2001-05-04	11325351
Presynaptic mechanisms underlying cannabinoid inhibition of excitatory synaptic transmission in rat striatal neurons.	2001-05-01	11313442
Seizure-like activity in the disinhibited CA1 minislice of adult guinea-pigs.	2001-05-01	11313441
The functional role of a bicuculline-sensitive Ca2+-activated K+ current in rat medial preoptic neurons.	2001-05-01	11313434
Ionotropic histamine receptors and H2 receptors modulate supraoptic oxytocin neuronal excitability and dye coupling.	2001-05-01	11312281
Effects of serotonin, GABA and neuropeptide Y on seabream gonadotropin releasing hormone release in vitro from preoptic-anterior hypothalamus and pituitary of red seabream, Pagrus major.	2001-05	11328447
Effects of retigabine on rhythmic synchronous activity of human neocortical slices.	2001-05	11325571
Polysynaptic excitatory pathways induce heterosynaptic depression in the rat auditory cortex.	2001-05	11311407
Effect of alpha subunit on allosteric modulation of ion channel function in stably expressed human recombinant gamma-aminobutyric acid(A) receptors determined using (36)Cl ion flux.	2001-05	11306694
GABAergic modulation of ventilation and peak oxygen consumption in obese Zucker rats.	2001-05	11299259
Unitary synaptic currents between lacunosum-moleculare interneurones and pyramidal cells in rat hippocampus.	2001-04-15	11306657
Rapid signaling at inhibitory synapses in a dentate gyrus interneuron network.	2001-04-15	11306622
GABA transaminase inhibition induces spontaneous and enhances depolarization-evoked GABA efflux via reversal of the GABA transporter.	2001-04-15	11306616
Cataleptic effect of neurosteroid 3alpha-hydroxy-5alpha-pregnan-20-one in mice: modulation by serotonergic agents.	2001-04-13	11292445
Endogenous acetylcholine facilitates epileptogenesis in immature rat neocortex.	2001-04-13	11278103
Acute exposure to trichloroethylene differentially alters the susceptibility to chemoconvulsants in mice.	2001-04-12	11311456
The anxiolytic effect of allopregnanolone is associated with gonadal hormonal status in female rats.	2001-04-06	11301065
Functional modulation of gamma-aminobutyric acid(A) receptors by etifoxine and allopregnanolone in rodents.	2001-04-06	11257430
Contribution of intralaminar thalamic nuclei to spike-and-wave-discharges during spontaneous seizures in a genetic rat model of absence epilepsy.	2001-04	11328348
NMDA-evoked calcium transients and currents in the suprachiasmatic nucleus: gating by the circadian system.	2001-04	11298803
Spontaneous GABAergic postsynaptic currents in Cajal-Retzius cells in neonatal rat cerebral cortex.	2001-04	11298799
The effects of propofol in the area postrema of rats.	2001-04	11273930
Distinct functional and pharmacological properties of tonic and quantal inhibitory postsynaptic currents mediated by gamma-aminobutyric acid(A) receptors in hippocampal neurons.	2001-04	11259626
Central GABAergic mechanisms are involved in apnea induced by SLN stimulation in piglets.	2001-04	11247962
Effect of beta-estradiol on voltage-gated Ca(2+) channels in rat hippocampal neurons: a comparison with dehydroepiandrosterone.	2001-03-30	11290370
Effects of pituitary adenylate cyclase activating polypeptide on lumbosacral preganglionic neurons in the neonatal rat spinal cord.	2001-03-23	11259781
Cardiorespiratory and metabolic responses to injection of bicuculline into the hypothalamic paraventricular nucleus (PVN) of conscious rats.	2001-03-23	11259757
Female gastrin-releasing peptide receptor (GRP-R)-deficient mice exhibit altered social preference for male conspecifics: implications for GRP/GRP-R modulation of GABAergic function.	2001-03-16	11251202
Involvement of GABA in medullary raphe-evoked modulation of neuronal activity in the periaqueductal grey matter in the rat.	2001-03	11315550
Immortalized gonadotropin-releasing hormone neurons (GT1-7 cells) exhibit synchronous bursts of action potentials.	2001-03	11307034
Anticonvulsant properties and bio-guided isolation of palmitone from leaves of Annona diversifolia.	2001-03	11301859
Endogenous cannabinoids mediate retrograde signals from depolarized postsynaptic neurons to presynaptic terminals.	2001-03	11301031
GABA(A) receptors in the ventral tegmental area control bidirectional reward signalling between dopaminergic and non-dopaminergic neural motivational systems.	2001-03	11264674
Acute phenobarbital administration induces hyperalgesia: pharmacological evidence for the involvement of supraspinal GABA-A receptors.	2001-03	11262592
Distinct effect of pregnenolone sulfate on NMDA receptor subtypes.	2001-03	11249958
2-deoxyglucose enhances epileptic tolerance evoked by transient incomplete brain ischemia in mice.	2001-03	11248539
Immunocytochemical and electrophysiological characterization of GABA receptors in the frog and turtle retina.	2001-03	11248259
Excitatory synaptic input to granule cells increases with time after kainate treatment.	2001-03	11247977
Expansion of receptive fields in raccoon somatosensory cortex in vivo by GABA(A) receptor antagonism: implications for cortical reorganization.	2001-02	11291725
Induction of wakefulness and inhibition of active (REM) sleep by GABAergic processes in the nucleus pontis oralis.	2001-02	11256181
The pharmacodynamics of anticonvulsant and subconvulsant effects of ethanol in CBA and C57BL/6 mice.	2001-01	11282448
Effects of sweetened ethanol solutions on ethanol self-administration and blood ethanol levels.	2001-01	11274703
The polysialylated neural cell adhesion molecule reaches cell surfaces of hypothalamic neurons and astrocytes via the constitutive pathway.	2001	11311794
GABA(A) agents injected into the ventral pallidum differentially affect dopaminergic pivoting and cholinergic circling elicited from the shell of the nucleus accumbens.	2001	11311536
GABA promotes survival but not proliferation of parvalbumin-immunoreactive interneurons in rodent neostriatum: an in vivo study with stereology.	2001	11311534
Fragile X mice develop sensory hyperreactivity to auditory stimuli.	2001	11301211
Effects of neurotensin on discharge rates of rat suprachiasmatic nucleus neurons in vitro.	2001	11274786
Slow inhibitory potentials in the teleost Mauthner cell.	2001	11246169

Patents

Sample Use Guides

In Vivo Use Guide

Chicks of 4–6 days old weighing approximately 100 g were used in the experiments. Bicuculline was dissolved in 0.85% saline and intraperitoneally (i.p.)injected at doses of 0.0036, 0.036, 0.36 and 36 mg/kg body weight at a final volume of 100 mkL. The final dose of bicuculline methiodideused for co-administration with ghrelin produced no behavioral effects per se.

Route of Administration: Intraperitoneal

In Vitro Use Guide

Rat primary cortical cultures was used for study spontaneous and pharmacologically-induced neural network function. Changes in number of total extracellularly-recorded action potential spikes (total spikes; TS) and active electrodes (AE), relative to controls, were assessed 1, 24, and 48 h after exposure to AgNO3. After the 48 h recording, the response to a pharmacological challenge with the GABAA antagonist, bicuculline (25uM), was assessed.

Name

Type

Language

BICUCULLINE

Common Name

English

NSC-32192

Preferred Name

English

BICUCULLINE [MI]

Common Name

English

(6R)-6-((5S)-6-METHYL-5,6,7,8-TETRAHYDRO(1,3)DIOXOLO(4,5-G)ISOQUINOLIN-5-YL)FURO(3,4-E)(1,3BENZODIOXOL-8(6H)-ONE

Common Name

English

Code System Code Type Description

WIKIPEDIA

BICUCULLINE