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Product name: Bicuculline
Synonym name: (+)-Bicuculline; d-Bicuculline
Catalogue No.: BP0273
Cas No.: 485-49-4
Formula: C20H17NO6
Mol Weight: 367.357
Botanical Source: Corydalis decumbens （Thunb. ）Pers.
Physical Description:
Type of Compound: Alkaloids
Purity: 95%~99%
Analysis Method: HPLC-DAD or/and HPLC-ELSD
Identification Method: Mass, NMR
Packing: Brown vial or HDPE plastic bottle
Storage: Store in a well closed container, protected from air and light. Put into refrigerate or freeze for long term storage.
Whenever possible, you should prepare and use solutions on the same day. However, if you need to make up stock solutions in advance, we recommend that you store the solution as aliquots in tightly sealed vials at -20℃. Generally, these will be useable for up to two weeks.
The product could be supplied from milligrams to grams
Inquire for bulk scale.
Chengdu Biopurify Phytochemicals Ltd. is a leading company in the research, development, manufacture and marketing of High Quality Phytochemicals and Extracts(especially Active Ingredients from Traditional Chinese Medicine，TCM), Natural Active Pharmaceutical Ingredients worldwide.
The main services:
A. Supply active ingredients and reference standards of TCM, from mgs to kgs scale
B. Custom extraction and purification, target Herb Active Ingredients
C. Custom synthesis and semi-synthesis for Natural Active Ingredients
D. CR(contract research), CM(contract manufacture) and PD(process development) services from lab scale, pilot scale to commercial scale(GMP is also available)
E. TCM compounds library for drug screen,more than 3000 compounds available, many of them are rare and unique.
HPLC of Bicuculline
Storage conditions：Short-term storage at 2~8℃, long-term storage at -20 ~ -80℃
92.0700
1.4900
1.4900
High
.7400
No
No
No
Unknown
No
Unknown
Bicuculline is a natural product with significant neuropharmacological significance, belonging to the benzyl isoquinoline alkaloids. First discovered in 1932 from plant alkaloid extracts, Bikokoulin attracted widespread attention due to its selective antagonistic effects on specific receptors in the central nervous system. As a competitive antagonist of γ-aminobutyric acid type A receptor (GABA_A receptor), Bikoukouling plays an important role in neuroexcitability regulation, seizure mechanism research, and neuropharmacology. This paper will systematically review the chemical structure and physicochemical properties of Bikoukouling, plant origin and extraction methods, pharmacological activity and mechanism of action, druggability evaluation, and pharmacokinetic characteristics, and explore its potential prospects and challenges in clinical application.
The chemical structure of Bikoukouling is 6-methyl-5,6,7,8-tetrahydro[1,3]dioxahecyclo[4,5-g]isoquinoline, with its 5-pro-S position replaced by (6R)-8-oxo-6,8-dihydrofuran-[3,4-e][1,3]benzodioxacyclopentene-6-yl. This structure gives Bikoukouling a unique spatial configuration and biological activity. Its molecular weight is 367.35, and its LogP value is 1.49, indicating moderate lipid solubility, which is beneficial for crossing the blood-brain barrier. The topological pole surface area (TPSA) is 92.07, and the number of hydrogen bond acceptors is 7, indicating moderate molecular polarity and the ability to form multi-point binding with the receptor.
The physicochemical properties of Bikou Ling give it good bioavailability and nervous system penetration in the body. The isoquinoline ring and furan unring system in its structure provide key spatial sites for binding to GABA_A receptors. Additionally, Bikoukouling does not show significant hepatotoxicity, cardiotoxicity, or hERG channel inhibition, indicating good safety potential.
Bikokouling was first isolated from Dicentra cucullaria, a plant of the Pelastaceae family, and was later found in Adlumia fungosa, Fumariaceae, and various Corydalis spp. species. These plants are widely distributed in North America and parts of Asia, and have traditionally been used in folk medicine for treating neurological diseases.
Common methods for extracting Bikouling include organic solvent extraction extraction, acid-base separation, and column chromatography purification. Typically, ethanol or methanol is used for reflux extraction of dried plant materials, followed by acid-base adjustment to precipitate the alkaloid as hydrochloride, followed by alkalization to release free alkalis, followed by solvent extraction and silica gel column chromatography for separation and purification. In recent years, ultrasound-assisted extraction and high-performance liquid chromatography (HPLC) technologies have been introduced to improve extraction efficiency and purity.
As a competitive antagonist of GABA_A receptors, Bikokoulin exhibits significant excitatory effects in the nervous system. GABA_A receptors are the main inhibitory neurotransmitter receptors in the central nervous system, mediating the opening of chloride ion channels, leading to neuronal hyperpolarization and inhibitory synaptic transmission. Bikoukouling competes for GABA binding sites, blocking the influx of GABA-mediated chloride ions, relieving neuronal inhibition, and inducing neuronal excitation.
In vitro and in vivo experiments, Bikouling has been widely used to induce epileptic discharges and neural excitability models, becoming an important tool for studying seizure mechanisms. It has high affinity for GABA_A receptors of various neuronal subtypes, significantly enhancing neuronal excitatory responses. In addition, Bikoukoulin also affects the functions of calcium channels (CACNA1H, CACNA1A) and potassium channels (KCNQ2), which are involved in regulating neuronal membrane potential and excitability.
The main molecular target of Bikoukoulin is GABA_A receptors, especially receptor complexes containing GABRA1 and GABRB2 subunits. By competitively binding to the ligand-binding site of the GABA receptor, Bikoulin blocks GABA-mediated chloride channel opening, reducing inhibitory neurotransmission, and increasing neuronal excitability.
In addition, the effects of Bikoukouling involve various epilepsy-related ion channels and receptor proteins, including:
By modulating the functions of these targets, Bikoukouling indirectly affects the excitability balance of neurons, making it an important molecular tool for studying neuroexcitatory diseases such as epilepsy.
The druggability parameters of Bikoukouling indicate that it has good pharmacokinetic potential. The molecular weight is moderate, and the LogP value indicates moderate lipid solubility, which facilitates blood-brain barrier penetration and meets the ideal characteristics of central nervous system drugs. Its TPSA and hydrogen bond receptor counts are moderate, supporting its high affinity for binding to targets.
In terms of safety, Bikoukouling did not show significant hepatotoxicity or cardiotoxicity, nor did it inhibit hERG channels, reducing the risk of arrhythmias. Although the results of Ames' mutagenicity tests are not yet clear, existing data support its safe application in neuropharmacological research.
Pharmacokinetic studies have shown that Bikoukouling is well absorbed orally, has high blood-brain barrier permeability, and can rapidly reach central nervous system targets. Its metabolic pathway is mainly metabolized by hepatic enzyme systems, and the activity and toxicity of these metabolites require further research.
As a classic GABA_A receptor antagonist, Bikouling is mainly used in basic neuroscience research, especially in the fields of seizure mechanisms and neuroexcitatory regulation. Its ability to induce epileptic-like seizures makes it an important tool for establishing animal epilepsy models, providing a powerful means for screening antiepileptic drugs and mechanistic studies.
Although Bikoukoulin itself has limited its direct clinical application due to its strong neuroexcitatory effects and potential epileptic risk, its structure and mechanism of action provide an important molecular basis for designing novel GABA_A receptor modulators. In the future, through structural modification and drug design, it is expected that derivatives with selective modulatory functions and higher safety will be developed to treat epilepsy and other neurological diseases.
In addition, the application of Bikoukouling in neuropharmacological research can be extended to exploring the pathological mechanisms of diseases such as cognitive impairment and anxiety disorders, providing theoretical support for related drug development.
As an important natural product, Bikoukouling holds an irreplaceable position in neuroscience research due to its unique chemical structure and photosensitive competitive antagonism of GABA_A receptors. Its application in the study of seizure mechanisms has greatly advanced neuropharmacology. Although Bikouling has not yet become a clinical therapeutic drug, its favorable druggability parameters and clear mechanism of action lay a solid foundation for the development of new neuromodulators in the future. With advances in molecular pharmacology and drug design technologies, the potential of Bikoulin and its derivatives in the treatment of neurological diseases deserves ongoing attention and deeper exploration.
Shenshuai
Wenjing
Hedandan
