Synonym name:
Catalogue No.: BP0728
Cas No.: 11041-94-4
Formula: C16H18ClNO3
Mol Weight: 307.774
Botanical Source:
Purity: 95%~99%
Analysis Method: HPLC-DAD or/and HPLC-ELSD
Identification Method: Mass, NMR
Packing: Brown vial or HDPE plastic bottle
Can be supplied from milligrams to grams.
For Reference Standard and R&D, Not for Human Use Directly.
Inquire for bulk scale.
Storage conditions：Short-term storage at 2~8℃, long-term storage at -20 ~ -80℃
Higenamine hydrochloride (CAS number: 11041-94-4) is an important natural alkaloid that was first isolated from the traditional Chinese medicine Aconitum spp. As a bioactive molecule, demethylamine hydrochloride has gradually received attention in pharmacological research in recent years, demonstrating broad application potential due to its multi-target and multifunctional pharmacological properties. Its main activities include selective LSD1 (lysine specific demethylase 1) inhibition, anti-inflammatory, antibacterial, and neuroprotective functions. In addition, norepinephrine hydrochloride has shown significant effects in inhibiting cell apoptosis and promoting bone formation by regulating signaling pathways such as PI3K/Akt and SMAD2/3, involving multiple fields such as cardiovascular protection, osteoporosis, cancer, and inflammatory diseases.
The purpose of this article is to systematically review the chemical structure, sources, and extraction methods of norepinephrine hydrochloride, elaborate on its pharmacological activity and mechanism of action, and explore its clinical application prospects and development directions based on drug parameters and pharmacokinetic characteristics, providing scientific basis for subsequent basic and clinical research.
The chemical name of the hydrochloride salt of levocetirizine is (S) -1- (4-hydroxyphenyl) -2-methylaminoethanol hydrochloride, with a molecular formula of C16H17NO3 · HCl and a molecular weight of 271.3160. Its structural core is a phenylethanolamine skeleton, which contains a para hydroxy benzene ring and a chiral center, and has strong hydrophilicity and certain lipophilicity. The LogP value is 1.5134, indicating that it has moderate lipid solubility, which is beneficial for cell membrane penetration but still has good water solubility (solubility 1.3347 mg/mL). The topological polar surface area (TPSA) is 72.72 Å ², indicating moderate polarity that may affect oral absorption and blood-brain barrier permeability.
The hydrochloride form of norepinephrine hydrochloride improves its water solubility and stability, making it easier for formulation development. Its blood-brain barrier penetration ability is relatively low, indicating limited direct action in the central nervous system, but exerting neuroprotective effects through peripheral mechanisms. The negative result of hERG channel inhibition experiment indicates a low risk of cardiac toxicity. The Ames mutagenicity test result is 0.6, indicating that its genotoxicity risk is low and meets drug safety requirements.
Noraconitine hydrochloride mainly exists in plants of the Aconitum genus, especially in the rhizomes of Aconitum carmichaelii and related species. Aconitum plants play an important role in traditional Chinese medicine and are commonly used for pain relief, anti-inflammatory, and treatment of cardiovascular diseases. Noraconitine, as one of the active ingredients, although its content is not as high as major alkaloids such as aconitine, it has attracted much attention due to its unique pharmacological effects.
The traditional extraction method usually uses alcohol solvents (such as ethanol and methanol) for reflux extraction of dried plant rhizomes, followed by purification through acid-base adjustment and liquid-liquid distribution, combined with column chromatography techniques (such as silica gel column, C18 reverse phase column). In recent years, the application of ultrasound assisted extraction and microwave-assisted extraction technologies has improved extraction efficiency and purity. High performance liquid chromatography (HPLC) and mass spectrometry techniques are widely used for qualitative and quantitative analysis of berberine, ensuring the quality and stability of the extract.
Noraconitine hydrochloride, as a selective LSD1 inhibitor, has an IC50 of approximately 1.47 μ M and can effectively inhibit the demethylation activity of LSD1. LSD1, as a histone demethylase, plays a crucial role in gene expression regulation and tumor development. Noraconitine exhibits potential anti-tumor activity by inhibiting LSD1 and regulating the epigenetic state of tumor cells.
Noraconitine hydrochloride has significant anti-inflammatory effects. Both in vitro and in vivo experiments have shown that it can inhibit the release of inflammatory mediators and alleviate inflammatory reactions. Its anti-inflammatory mechanism involves downregulating the activity of pro-inflammatory cytokines such as IL-1 β, TNF - α, and NF - κ B signaling pathways. In addition, demethylamine has inhibitory effect on a variety of bacteria, especially gram-positive bacteria, suggesting its potential application in infectious diseases.
Noraconitine hydrochloride can attenuate IL-1 β - induced neuronal apoptosis through the ROS mediated PI3K/Akt signaling pathway, protecting brain cells from hypoxia ischemia injury. This mechanism activates cell survival signals, inhibits the expression of apoptosis related proteins, reduces oxidative stress and inflammatory responses, demonstrating its potential therapeutic value in stroke and neurodegenerative diseases.
The latest research shows that norepinephrine promotes osteoblast differentiation and bone formation through the SMAD2/3 signaling pathway, and has the effect of improving osteoporosis. This mechanism provides new targets and ideas for drug development of bone metabolism diseases.
Noraconitine hydrochloride exhibits multiple protective effects in the cardiovascular system. Its targets include SELP, PPARG, ACE, AKT1, ADRB2, KCNH2, NOS3, ICAM1, VCAM1, and SLC8A1, involving multiple aspects such as vasodilation, anti-inflammatory, antioxidant, myocardial protection, and electrophysiological stability. Noraconitine has potential adjuvant therapeutic value for heart failure and myocardial infarction by activating β 2 adrenergic receptors (ADRB2) and regulating the activity of NO synthase (NOS3), improving hemodynamics, and reducing myocardial ischemic injury.
The mechanism of action of norepinephrine hydrochloride is complex and diverse, mainly achieved through the following signaling pathways and molecular targets:
LSD1 inhibition By competitively inhibiting LSD1 enzyme activity, regulating histone methylation status, affecting gene transcription, and inhibiting tumor cell proliferation and migration.
PI3K/Akt signaling pathway Noraconitine activates the PI3K/Akt pathway, promotes cell survival, inhibits the production of inflammatory mediators, reduces oxidative stress and cell apoptosis, and protects nerve cells and cardiomyocytes.
SMAD2/3 signaling pathway By activating TGF - β - related SMAD2/3 signaling, promoting osteoblast differentiation, enhancing bone formation, and improving osteoporosis.
Activation of β 2 adrenergic receptors (ADRB2)Noraconitine, as an agonist of ADRB2, regulates heart rate and vasodilation, and improves cardiovascular function.
Anti inflammatory targets Downregulate inflammation related molecules such as Selectin (SELP), Intercellular Adhesion Molecules (ICAM1, VCAM1), and PPARG to inhibit leukocyte adhesion and inflammatory response.
Electrophysiological regulation By affecting potassium channel KCNH2 and calcium ion exchange protein SLC8A1, stabilizing myocardial cell membrane potential and preventing arrhythmia.
In summary, the hydrochloride salt of berberine exerts its wide-ranging pharmacological effects through multi-target and multi pathway synergistic effects.
The pharmacological evaluation of norepinephrine hydrochloride shows that it has good potential for drug development. The molecular weight is 271.3160, in accordance with Lipinski's rule, with a LogP of 1.5134. Moderate lipid solubility is beneficial for oral absorption. The TPSA is 72.72 Å ², indicating that it has moderate polarity and is conducive to passing through the cell membrane but has low permeability through the blood-brain barrier.
Good water solubility (1.3347 mg/mL), convenient for formulation development and in vivo delivery. The hERG channel inhibition experiment results were negative, reducing the risk of cardiac toxicity. The Ames test results showed no significant mutagenicity and high safety.
In terms of pharmacokinetics, the oral bioavailability of norepinephrine hydrochloride is moderate, and it is widely distributed in the body but has a low concentration in brain tissue. Metabolism is mainly through the liver CYP450 enzyme system, and the safety of metabolites is good. The main excretion pathway is renal excretion. Moderate half-life, suitable for daily administration.
At present, there is a lack of systematic clinical pharmacokinetic studies, and in the future, it is necessary to further clarify its in vivo pharmacokinetic characteristics and drug interactions.
Noraconitine hydrochloride has shown broad clinical application potential in multiple disease fields due to its multiple pharmacological activities.
tumor therapy As an LSD1 inhibitor, demethylamine can regulate the epigenetic state of tumor cells, inhibit tumor growth and metastasis, and is expected to be developed as a new anti-tumor drug in the future, especially in combination with chemotherapy or immunotherapy.
cardiovascular disease Its comprehensive effects on myocardial protection, vasodilation, and anti-inflammatory are suitable for adjuvant treatment of diseases such as myocardial ischemia, heart failure, and arrhythmia, improving patient prognosis.
neuroprotection By inhibiting inflammation and oxidative stress, reducing neuronal apoptosis, norepinephrine is expected to be used for the prevention and treatment of stroke and neurodegenerative diseases.
osteoporosis The role of promoting bone formation provides new ideas for the treatment of osteoporosis and can be developed as a bone metabolism regulator in the future.
Inflammation and infection Its anti-inflammatory and antibacterial activities make it a potential therapeutic drug for inflammatory diseases and infectious diseases.
Despite the multifaceted therapeutic potential of norepinephrine hydrochloride, its clinical application still faces many challenges, such as systematic clinical safety and efficacy validation, dosage form optimization, and pharmacokinetic refinement. Future research should focus on in-depth mechanism analysis, clinical trial design, and combination therapy strategies to promote their clinical translation.
Noraconitine hydrochloride, as a multifunctional natural product, has shown unique advantages in pharmacological research. Its selective LSD1 inhibitory effect and multi-target regulatory ability make it widely applicable in fields such as tumors, cardiovascular disease, neuroprotection, and bone metabolism. Based on good pharmacokinetic parameters and safety evaluation, demethylamine hydrochloride has the potential to become a new drug candidate molecule.
Future research needs to strengthen the systematic elucidation of its mechanism of action, improve pharmacokinetic and toxicological data, conduct multicenter clinical trials, and promote its clinical application and translation. The in-depth development of norepinephrine hydrochloride not only enriches the research content of natural product pharmacology, but also provides new drug resources and strategies for the treatment of related diseases.
