Product name: Guvacine HCl
Synonym name: Guvacine 498-96-4
Catalogue No.: BP4087
Cas No.: 6027-91-4
Formula: C₆H₉NO₂(Free Base)
Mol Weight: 127.143
Botanical Source: 1,2,5,6-Tetrahydronicotinic acid
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.

For Reference Standard and R&D, Not for Human Use Directly.

Storage conditions：Short-term storage at 2~8℃, long-term storage at -20 ~ -80℃

Introduction/Overview

Guvacine HCl hydrochloride (CAS number: 6027-91-4) is a naturally occurring alkaloid found in Areca catechu, which has attracted attention for its unique neuromodulatory activity. As an effective inhibitor of γ-aminobutyric acid (GABA) uptake, desmethylacezoine hydrochloride holds significant pharmacological value in neuroscience research. As the main inhibitory neurotransmitter of the central nervous system, GABA's uptake regulation is crucial for maintaining the balance between neural excitation and inhibition. Noracezodiamine hydrochloride demonstrates the potential to regulate neurotransmitter dynamics by inhibiting GABA transporters (GATs), especially GAT-1, GAT-2, and GAT-3, thereby influencing the pathological processes of various neuropsychiatric diseases.

In recent years, with deeper understanding of neuroregulatory mechanisms, the mechanism, molecular targets, and druggability parameters of desmethylene arecaine hydrochloride have gradually been revealed, promoting its potential application research in the treatment of neurological diseases. This paper aims to systematically review the chemical structure and physicochemical properties, plant origin and extraction methods, pharmacological activity, mechanism of action, druggability evaluation, and clinical application prospects of Arcane Hydrochloride, aiming to provide scientific basis and research directions for further development of this compound.

Chemical structure and physicochemical properties

The molecular formula of demethylated betel quarine hydrochloride is C6H13NO2, and its molecular weight is 127.1430. Its structure is an organic base containing nitrogen atoms, specifically in the hydrochloride form of desmethyl betel quacaine. The compound had a LogP value of -1.9524, indicating strong hydrophilicity and good water solubility (54.2116 mg/mL), which positively affects the bioavailability and distribution of the drug. Its topological pole surface area (TPSA) is 49.33 Ų, suggesting that its molecules have moderate polarity, which facilitates penetration of biological membranes.

Norbetel anine hydrochloride has a high blood-brain barrier (BBB) penetration capacity, which is especially important for central nervous system drugs. It does not inhibit hERG channels, and the Ames-induced mutagenic test result is 0.0, indicating high safety and low toxicity risk. These physicochemical and safety parameters lay a solid foundation for its development as a nervous system drug.

Plant Origins and Extraction Methods

Areca catechu hydrochloride is mainly found in Areca catechu, a plant of the Areca genus in the palm family, widely distributed in tropical Asia. The seeds and fruits of betel nut are rich in various alkaloids, with betel nut quacine and its derivatives being the main components, with acetomethylene quacine hydrochloride being one of its key components.

Traditional extraction methods mostly use solvent extraction combined with acid-base separation technology. The specific steps include: crushing dried betel nut, extracting with ethanol or methanol, then concentrating the extract and adjusting the pH to acidity with hydrochloric acid to form hydrochloric acid to improve water solubility. Then, through liquid-liquid extraction and column chromatography, high-purity demethylated betel nut hypochloride hydrochloride was obtained. Modern extraction technologies such as ultrasound-assisted extraction and microwave-assisted extraction are also applied to improve extraction efficiency and purity.

Moreover, given the wide variety of alkaloids in betel nut, process parameters must be strictly controlled during extraction to avoid component degradation and impurity mixing, ensuring products that meet medicinal standards.

Pharmacological activity research

Noracezodiachloride hydrochloride, as a GABA uptake inhibitor, mainly focuses on regulating inhibitory neurotransmission in the central nervous system. In vitro experiments showed that this compound inhibited rat GABA transporters GAT-1, GAT-2, and GAT-3 in a concentration-dependent manner, with IC50s of 39 μM, 58 μM, and 378 μM, indicating more significant inhibition of GAT-1 and GAT-2.

GAT-1 is mainly distributed in neurons and astrocytes, responsible for GABA reuptake and clearance, and regulates GABA concentration in the synaptic cleft. GAT-2 and GAT-3 are mainly found in cerebrospinal fluid and astrocytes, and are involved in nonsynaptic regulation of GABA. Normelanine diachloride prolongs the duration of GABA action in the synaptic cleft by inhibiting these transport proteins, thereby enhancing GABA-mediated neuroinhibition.

Animal model studies have shown that nomethyl betel hydrochloride has anti-anxiety, antiepileptic, and neuroprotective effects. In anxiety models, this compound significantly reduced anxiety behaviors in animals, suggesting it may achieve anti-anxiety effects by enhancing GABAergic neurotransmission. In epilepsy models, dacecordine hydrochloride prolonged seizure latency, reduced seizure frequency, and demonstrated good antiepileptic potential. Additionally, its neuroprotective effect in models of neuronal ischemia-reperfusion injury suggests its application value in neurodegenerative diseases.

Mechanism of action and molecular targets

The core mechanism of Noracezoine hydrochloride is to inhibit GABA transporters, increase GABA concentration in the synaptic cleft, and enhance inhibitory neurotransmission mediated by GABA_A and GABA_B receptors. This mechanism is important for regulating neural excitability and maintaining neural network stability.

In addition to GABA transporters, nomethyl betel diachloride hydrochloride may also affect various neuroregulation-related targets, including monoamine oxidase A (MAOA), monoamine oxidase B (MAOB), α7 nicotinic acetylcholine receptor (CHRNA7), dopamine receptors (DRD1, DRD2, DRD3, DRD4, DRD5), and 5-hydroxytryptamine receptors (HTR1A, HTR2A). These targets play key roles in neurotransmitter metabolism, neural excitation regulation, and emotional regulation.

For example, MAOA and MAOB are involved in the metabolism of dopamine, norepinephrine, and serotonin, regulating mood and cognitive function; CHRNA7 receptors regulate cognition and neuroprotection; Dopamine receptors and serotonin receptors are directly involved in regulating emotions, behavior, and mental states. The regulatory effect of desmethyl betel hypochloride on these targets may work in conjunction with its GABAergic mechanisms to form a multi-target, multi-pathway neural regulatory network.

Molecular docking and in vitro binding experiments support the binding potential of desmethylacetabine hydrochloride to the aforementioned targets, suggesting its broad neuromodulatory activity and providing a theoretical basis for developing new drugs targeting neuropsychiatric disorders such as depression, anxiety, and Parkinson's disease.

Druggability evaluation and pharmacokinetics

From the perspective of druggability, demethylene betel nutine hydrochloride exhibits several favorable characteristics. Its molecular weight is relatively low (127.1430), conforming to the Lipinski rule, which is beneficial for oral absorption. A negative LogP value (-1.9524) indicates strong hydrophilicity, which helps dissolve and distribute in body fluids. TPSA was 49.33 Ų, below the 90 Ų threshold, indicating good cell membrane penetration capability, especially the ability to cross the blood-brain barrier.

Pharmacokinetics, Norane Arcanine Hydrochloride is expected to have good oral bioavailability due to its high water solubility and low molecular weight. Its high blood-brain barrier penetration enables it to effectively act on the central nervous system, meeting the key requirements of nervous system drugs. The metabolic pathway in vivo is not yet fully understood, but given its simple structure, relatively rapid metabolic transformation is likely mainly carried out through hepatic enzyme systems.

Safety evaluations showed that nophenylene bentoine hydrochloride did not inhibit hERG channels, reducing the risk of arrhythmias. The Ames test result was negative, indicating no significant genotoxicity. Additionally, preliminary toxicological studies have shown no obvious acute or subchronic toxicity, supporting further drug development.

Prospects and outlooks for clinical applications

Desmethylaceterine hydrochloride, as an effective GABA uptake inhibitor, has broad neuromodulation potential, especially promising applications in anxiety disorders, epilepsy, depression, and neurodegenerative diseases. Its multi-target mechanism of action offers possibilities for multidimensional treatment of complex neurological diseases, especially when single-target drugs have limited efficacy, where the multi-modulatory advantages of nophenylene aretabine hydrochloride are evident.

Future research should focus on the following aspects: first, systematic pharmacokinetic and toxicological evaluation to clarify their behavior and safe dosage range in vivo; Second, it deeply analyzes its interaction mechanisms with various neuroregulatory targets and reveals its multi-target synergistic effects; Third, conducting efficacy validation of preclinical animal models, especially targeting behavioral and physiological indicators of neuropsychiatric diseases; Fourth, explore its potential in combination therapy, especially in synergy with other neuromodulatory drugs.

In addition, based on the structural characteristics of desmethyl betel esine hydrochloride, chemical modification and drug design will also be effective strategies to enhance its efficacy and selectivity. By optimizing its structure, enhancing its selective inhibition of specific GABA transporter subtypes, or improving its pharmacokinetic performance, it will provide a more solid foundation for clinical translation.

Conclusion

Desmethyl betel hypoalkaloid hydrochloride, a natural alkaloid derived from betel nut, demonstrates broad research and application prospects in the field of neuroregulation due to its unique mechanism of inhibiting GABA uptake. Its excellent physicochemical properties, high blood-brain barrier penetration ability, and safety provide favorable conditions for its development as a neurologic drug. In the future, through in-depth pharmacological mechanism research, systematic pharmacokinetic and toxicological evaluations, and advancement of preclinical and clinical studies, nomethylene betel nut acid hydrochloride is expected to become a novel drug for treating various neuropsychiatric diseases, contributing to improving patients' quality of life.