Bicuculline
From DrugPedia: A Wikipedia for Drug discovery
| Bicuculline
| |
| Systematic (IUPAC) name | |
| (6R)-6-[(5S)-6-methyl-7,8-dihydro-5H-[1,3]dioxolo[4,5-g]isoquinolin-5-yl]-6H-furo[4,3-g][1,3]benzodioxol-8-one | |
| Identifiers | |
| CAS number | ? |
| ATC code | ? |
| PubChem | |
| Chemical data | |
| Formula | C20H17NO6 |
| Mol. mass | 367.35208 |
| SMILES | & |
| Pharmacokinetic data | |
| Bioavailability | ? |
| Metabolism | ? |
| Half life | ? |
| Excretion | ? |
| Therapeutic considerations | |
| Pregnancy cat. |
? |
| Legal status | |
| Routes | ? |
[edit] Description
Isoquinoline alkaloid from Dicentra cucullaria and other plants that is a competitive antagonist at GABA-A receptors and thus causes convulsions.
Bicuculline (BIC) 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 utilised 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.
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 — however in recent years a new class of ionotropic GABA receptor, defined variously as GABAA or GABAC has been characterised, which is insensitive to both benzodiazepines and bicuculline.
A water soluble form of bicuculline, bicuculline methiodide, is soluble in water to a concentration of 10 mg/mL.
[edit] General Properties
*Molecular Weight
367.35208
*Molecular Formula
C20H17NO6
*IUPAC NAME
(6R)-6-[(5S)-6-methyl-7,8-dihydro-5H-[1,3]dioxolo[4,5-g]isoquinolin-5-yl]-6H-furo[4,3-g][1,3]benzodioxol-8-one
*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
*XLogP
2.8
*Topological Polar Surface Area
66.5
