Bicuculline
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Basic Info
| Common Name | Bicuculline(F05219) |
| 2D Structure | |
| Description | 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. |
| FRCD ID | F05219 |
| CAS Number | 485-49-4 |
| PubChem CID | 10237 |
| Formula | C20H17NO6 |
| IUPAC Name | (6R)-6-[(5S)-6-methyl-7,8-dihydro-5H-[1,3]dioxolo[4,5-g]isoquinolin-5-yl]-6H-furo[3,4-g][1,3]benzodioxol-8-one |
| InChI Key | IYGYMKDQCDOMRE-ZWKOTPCHSA-N |
| InChI | 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 |
| Canonical SMILES | CN1CCC2=CC3=C(C=C2C1C4C5=C(C6=C(C=C5)OCO6)C(=O)O4)OCO3 |
| Isomeric SMILES | CN1CCC2=CC3=C(C=C2[C@H]1[C@H]4C5=C(C6=C(C=C5)OCO6)C(=O)O4)OCO3 |
| Synonyms |
(+)-Bicuculline
bicuculline
d-Bicuculline
485-49-4
Bicculine
Bicucullin
Bicuculline (+)
UNII-Y37615DVKC
NSC 32192
C20H17NO6
|
| Classifies |
Plant Toxin
|
| Update Date | Nov 13, 2018 17:07 |
Chemical Taxonomy
| Kingdom | Organic compounds |
| Superclass | Alkaloids and derivatives |
| Class | Phthalide isoquinolines |
| Subclass | Not available |
| Intermediate Tree Nodes | Not available |
| Direct Parent | Phthalide isoquinolines |
| Alternative Parents | |
| Molecular Framework | Aromatic heteropolycyclic compounds |
| Substituents | Phthalide isoquinoline - Benzofuranone - Phthalide - Isobenzofuranone - Tetrahydroisoquinoline - Benzodioxole - Isocoumaran - Aralkylamine - Benzenoid - Amino acid or derivatives - Carboxylic acid ester - Lactone - Tertiary amine - Tertiary aliphatic amine - Monocarboxylic acid or derivatives - Acetal - Carboxylic acid derivative - Oxacycle - Organoheterocyclic compound - Azacycle - Organic oxide - Organopnictogen compound - Organooxygen compound - Organonitrogen compound - Amine - Organic oxygen compound - Hydrocarbon derivative - Organic nitrogen compound - Aromatic heteropolycyclic compound |
| Description | This compound belongs to the class of organic compounds known as phthalide isoquinolines. These are organic compounds with a structure characterized by an isoquinoline moiety linked to phthalide. |
Properties
| Property Name | Property Value |
|---|---|
| Molecular Weight | 367.357 |
| Hydrogen Bond Donor Count | 0 |
| Hydrogen Bond Acceptor Count | 7 |
| Rotatable Bond Count | 1 |
| Complexity | 615 |
| Monoisotopic Mass | 367.106 |
| Exact Mass | 367.106 |
| XLogP | 2.6 |
| Formal Charge | 0 |
| Heavy Atom Count | 27 |
| Defined Atom Stereocenter Count | 2 |
| Undefined Atom Stereocenter Count | 0 |
| Defined Bond Stereocenter Count | 0 |
| Undefined Bond Stereocenter Count | 0 |
| Isotope Atom Count | 0 |
| Covalently-Bonded Unit Count | 1 |
ADMET
| Model | Result | Probability |
|---|---|---|
| Absorption | ||
| Blood-Brain Barrier | BBB+ | 0.9395 |
| Human Intestinal Absorption | HIA+ | 1.0000 |
| Caco-2 Permeability | Caco2+ | 0.8038 |
| P-glycoprotein Substrate | Substrate | 0.6883 |
| P-glycoprotein Inhibitor | Non-inhibitor | 0.6600 |
| Non-inhibitor | 0.8382 | |
| Renal Organic Cation Transporter | Inhibitor | 0.5210 |
| Distribution | ||
| Subcellular localization | Lysosome | 0.4400 |
| Metabolism | ||
| CYP450 2C9 Substrate | Non-substrate | 0.8238 |
| CYP450 2D6 Substrate | Non-substrate | 0.6170 |
| CYP450 3A4 Substrate | Substrate | 0.6451 |
| CYP450 1A2 Inhibitor | Inhibitor | 0.9107 |
| CYP450 2C9 Inhibitor | Inhibitor | 0.7664 |
| CYP450 2D6 Inhibitor | Non-inhibitor | 0.6229 |
| CYP450 2C19 Inhibitor | Inhibitor | 0.8993 |
| CYP450 3A4 Inhibitor | Inhibitor | 0.7959 |
| CYP Inhibitory Promiscuity | Low CYP Inhibitory Promiscuity | 0.5366 |
| Excretion | ||
| Toxicity | ||
| Human Ether-a-go-go-Related Gene Inhibition | Weak inhibitor | 0.9026 |
| Non-inhibitor | 0.9560 | |
| AMES Toxicity | Non AMES toxic | 0.7435 |
| Carcinogens | Non-carcinogens | 0.9600 |
| Fish Toxicity | High FHMT | 0.9286 |
| Tetrahymena Pyriformis Toxicity | High TPT | 0.8177 |
| Honey Bee Toxicity | Low HBT | 0.7016 |
| Biodegradation | Not ready biodegradable | 0.5435 |
| Acute Oral Toxicity | III | 0.7155 |
| Carcinogenicity (Three-class) | Non-required | 0.5613 |
| Model | Value | Unit |
|---|---|---|
| Absorption | ||
| Aqueous solubility | -3.1453 | LogS |
| Caco-2 Permeability | 1.5282 | LogPapp, cm/s |
| Distribution | ||
| Metabolism | ||
| Excretion | ||
| Toxicity | ||
| Rat Acute Toxicity | 2.4222 | LD50, mol/kg |
| Fish Toxicity | 0.8972 | pLC50, mg/L |
| Tetrahymena Pyriformis Toxicity | 0.4388 | pIGC50, ug/L |
References
| Title | Journal | Date | Pubmed ID |
|---|---|---|---|
| Apolipoprotein A-IV Inhibits AgRP/NPY Neurons and Activates Pro-Opiomelanocortin Neurons in the Arcuate Nucleus. | Neuroendocrinology | 2016 | 26337236 |
| GABA signalling modulates plant growth by directly regulating the activity of plant-specific anion transporters. | Nat Commun | 2015 Jul 29 | 26219411 |
| Prefrontal cortical GABA modulation of spatial reference and working memory. | Int J Neuropsychopharmacol | 2014 Oct 31 | 25552433 |
| Manipulation of GABA in the ventral pallidum, but not the nucleus accumbens, induces intense, preferential, fat consumption in rats. | Behav Brain Res | 2014 Aug 15 | 24867334 |
| Glutamic acid decarboxylase gene disruption reveals signalling pathway(s)governing complex morphogenic and metabolic events in Trichoderma atroviride. | Antonie Van Leeuwenhoek | 2013 Nov | 23912446 |
| Effects of GABA ligands injected into the nucleus accumbens shell on fear/anxiety-like and feeding behaviours in food-deprived rats. | Pharmacol Biochem Behav | 2012 Mar | 22130445 |
| Baclofen into the lateral parabrachial nucleus induces hypertonic sodium chlorideand sucrose intake in rats. | Neuroscience | 2011 Jun 2 | 21419196 |
| High-fat feeding alters the cardiovascular role of the hypothalamic paraventricular nucleus. | Am J Physiol Regul Integr Comp Physiol | 2010 Mar | 20042687 |
| GABAergic influences on ORX receptor-dependent abnormal motor behaviors and neurodegenerative events in fish. | Toxicol Appl Pharmacol | 2010 Feb 15 | 19931293 |
| Amygdala regulates risk of predation in rats foraging in a dynamic fear environment. | Proc Natl Acad Sci U S A | 2010 Dec 14 | 21115817 |
| The infralimbic cortex regulates the consolidation of extinction after cocaine self-administration. | Learn Mem | 2010 Apr | 20332188 |
| The effects of bicuculline and muscimol on glutamate-induced feeding behavior in broiler cockerels. | J Comp Physiol A Neuroethol Sens Neural Behav Physiol | 2009 Aug | 19415297 |
| Role of ventral medial prefrontal cortex in incubation of cocaine craving. | Neuropharmacology | 2009 | 18565549 |
| GABAergic mechanisms of the lateral parabrachial nucleus on sodium appetite. | Brain Res Bull | 2007 Jul 12 | 17562389 |
| Analysis of responses to kava kava in the feline pulmonary vascular bed. | J Med Food | 2006 Spring | 16579730 |
| GABA(A) receptors mediate orexin-A induced stimulation of food intake. | Neuropharmacology | 2006 Jan | 16168444 |
| Orexin A in the rostrolateral hypothalamic area induces feeding by modulating GABAergic transmission. | Brain Res | 2006 Dec 13 | 17092492 |
| GABA receptor subtype antagonists in the nucleus accumbens shell and ventraltegmental area differentially alter feeding responses induced by deprivation,glucoprivation and lipoprivation in rats. | Brain Res | 2006 Apr 12 | 16516868 |
| The neurotransmitters glycine and GABA stimulate glucagon-like peptide-1 release from the GLUTag cell line. | J Physiol | 2005 Dec 15 | 16223757 |
| GABA(A) receptor activation in the lateral parabrachial nucleus induces water and hypertonic NaCl intake. | Neuroscience | 2005 | 16009500 |
Targets
- General Function:
- Histamine receptor activity
- Specific Function:
- In peripheral tissues, the H1 subclass of histamine receptors mediates the contraction of smooth muscles, increase in capillary permeability due to contraction of terminal venules, and catecholamine release from adrenal medulla, as well as mediating neurotransmission in the central nervous system.
- Gene Name:
- HRH1
- Uniprot ID:
- P35367
- Molecular Weight:
- 55783.61 Da
References
- Kanba S, Richelson E: Histamine H1 receptors in human brain labelled with [3H]doxepin. Brain Res. 1984 Jun 18;304(1):1-7. [6146381 ]
- General Function:
- Inhibitory extracellular ligand-gated ion channel activity
- Specific Function:
- Component of the heteropentameric receptor for GABA, the major inhibitory neurotransmitter in the vertebrate brain. Functions also as histamine receptor and mediates cellular responses to histamine. Functions as receptor for diazepines and various anesthetics, such as pentobarbital; these are bound at a separate allosteric effector binding site. Functions as ligand-gated chloride channel (By similarity).
- Gene Name:
- GABRA1
- Uniprot ID:
- P14867
- Molecular Weight:
- 51801.395 Da
References
- Ebert B, Thompson SA, Saounatsou K, McKernan R, Krogsgaard-Larsen P, Wafford KA: Differences in agonist/antagonist binding affinity and receptor transduction using recombinant human gamma-aminobutyric acid type A receptors. Mol Pharmacol. 1997 Dec;52(6):1150-6. [9396785 ]
- General Function:
- Inhibitory extracellular ligand-gated ion channel activity
- Specific Function:
- GABA, the major inhibitory neurotransmitter in the vertebrate brain, mediates neuronal inhibition by binding to the GABA/benzodiazepine receptor and opening an integral chloride channel.
- Gene Name:
- GABRA3
- Uniprot ID:
- P34903
- Molecular Weight:
- 55164.055 Da
References
- Ebert B, Thompson SA, Saounatsou K, McKernan R, Krogsgaard-Larsen P, Wafford KA: Differences in agonist/antagonist binding affinity and receptor transduction using recombinant human gamma-aminobutyric acid type A receptors. Mol Pharmacol. 1997 Dec;52(6):1150-6. [9396785 ]
- General Function:
- Inhibitory extracellular ligand-gated ion channel activity
- Specific Function:
- GABA, the major inhibitory neurotransmitter in the vertebrate brain, mediates neuronal inhibition by binding to the GABA/benzodiazepine receptor and opening an integral chloride channel.
- Gene Name:
- GABRA6
- Uniprot ID:
- Q16445
- Molecular Weight:
- 51023.69 Da
References
- Ebert B, Thompson SA, Saounatsou K, McKernan R, Krogsgaard-Larsen P, Wafford KA: Differences in agonist/antagonist binding affinity and receptor transduction using recombinant human gamma-aminobutyric acid type A receptors. Mol Pharmacol. 1997 Dec;52(6):1150-6. [9396785 ]