Pale yellow crystalline powder
D-BICUCULLINE/BICUCULLINE (+)/(+)-Bicuculline/PLUS-BICUCULLINE/bicucculine/(6R)-6-[(5S)-6-Methyl-5,6,7,8-tetrahydro[1,3]dioxolo[4,5-g]isoquinolin-5-yl]furo[3,4-e][1,3]benzodioxol-8(6H)-one/Bicuculline/Furo[3,4-e]-1,3-benzodioxol-8(6H)-one, 6-[(5S)-5,6,7,8-tetrahydro-6-methyl-1,3-dioxolo[4,5-g]isoquinolin-5-yl]-, (6R)-/bicucullin
(+)-Bicuculline is a light-sensitive competitive antagonist of GABA-A receptor.
Chloroform; Ethyl Acetate; Benzene
542.3±50.0 °C at 760 mmHg
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Personal Projective Equipment
For Reference Standard and R&D, Not for Human Use Directly.
provides coniferyl ferulate(CAS#:485-49-4) MSDS, density, melting point, boiling point, structure, formula, molecular weight etc. Articles of coniferyl ferulate are included as well.>> amp version: coniferyl ferulate
Benzodiazepines (BZDs) produce various pharmacological actions by binding to and allosterically regulating GABAA receptors. Several in vitro studies have demonstrated diazepam, the prototypic BZD, produces a high-dose action that cannot be countered with the classical BZD-binding site antagonist flumazenil. Here, we investigate the existence and behavioral relevance of non-classical BZD binding sites in zebrafish larvae.
Zebrafish larvae were treated with a series of BZDs alone or combined with flumazenil, bicuculline (a non-selective GABAA receptor antagonist), or RO 15-4513 (a general BZD antagonist and a proposed antagonist interacting with α+/β- interfaces in α4/6/β3δ receptors), and their locomotor activities and behavioral phenotypes were recorded.
Diazepam-induced hypolocomotion (sedation-like state) at low doses (10 and 20 mg L-1) was effectively antagonized by flumazenil or bicuculline, while diazepam-induced immobility (anesthesia-like state) at higher dose (30 mg L-1) was prevented by bicuculline (3 mg L-1) but not flumazenil, even at doses up to 150 mg L-1. Ro 15-4513 also failed to efficiently antagonize diazepam-induced immobility. Immobility induced by high dose of another 1,4-BZD, clonazepam, was also resistant to flumazenil.
These results provide direct in vivo evidence for non-classical BZD-binding sites, which may be located at the second transmembrane domain of GABAA receptors and contribute to BZD-induced anesthesia.
Copyright © 2019 Elsevier Inc. All rights reserved.
Benzodiazepine; GABA(A) receptor; Immobility; Nonclassical binding site; Zebrafish
Flumazenil-insensitive benzodiazepine binding sites in GABAA receptors contribute to benzodiazepine-induced immobility in zebrafish larvae.
Cao Y1, Yan H1, Yu G2, Su R3.
2019 Dec 15
Basal forebrain; Bicuculline; Feeding; Locomotion
Dissociable effects of dopamine D1 and D2 receptors on compulsive ingestion and pivoting movements elicited by disinhibiting the ventral pallidum.
Reichard RA1,2, Parsley KP3, Subramanian S3, Zahm DS4.
GABAA receptors (GABAARs) are targets for important classes of clinical agents (e.g., anxiolytics, anticonvulsants, and general anesthetics) that act as positive allosteric modulators (PAMs). Previously, using photoreactive analogs of etomidate ([3H]azietomidate) and mephobarbital [[3H]1-methyl-5-allyl-5-(m-trifluoromethyl-diazirynylphenyl)barbituric acid ([3H]R-mTFD-MPAB)], we identified two homologous but pharmacologically distinct classes of general anesthetic binding sites in the α1β3γ2 GABAAR transmembrane domain at β +-α – (β + sites) and α +-β -/γ +-β – (β – sites) subunit interfaces. We now use competition photolabeling with [3H]azietomidate and [3H]R-mTFD-MPAB to identify para-substituted propofol analogs and other drugs that bind selectively to intersubunit anesthetic sites. Propofol and 4-chloro-propofol bind with 5-fold selectivity to β +, while derivatives with bulkier lipophilic substitutions [4-(tert-butyl)-propofol and 4-(hydroxyl(phenyl)methyl)-propofol] bind with ∼10-fold higher affinity to β – sites. Similar to R-mTFD-MPAB and propofol, these drugs bind in the presence of GABA with similar affinity to the α +-β – and γ +-β – sites. However, we discovered four compounds that bind with different affinities to the two β – interface sites. Two of these bind with higher affinity to one of the β – sites than to the β + sites. We deduce that 4-benzoyl-propofol binds with >100-fold higher affinity to the γ +-β – site than to the α +-β – or β +-α – sites, whereas loreclezole, an anticonvulsant, binds with 5- and 100-fold higher affinity to the α +-β – site than to the β + and γ +-β – sites. These studies provide a first identification of PAMs that bind selectively to a single intersubunit site in the GABAAR transmembrane domain, a property that may facilitate the development of subtype selective GABAAR PAMs.
Copyright © 2019 by The American Society for Pharmacology and Experimental Therapeutics.
Identifying Drugs that Bind Selectively to Intersubunit General Anesthetic Sites in the α1β3γ2 GABAAR Transmembrane Domain.
Jayakar SS1, Zhou X1, Chiara DC1, Jarava-Barrera C1, Savechenkov PY1, Bruzik KS1, Tortosa M1, Miller KW1, Cohen JB2.