Product name: Mesaconitine
Synonym name: N-Desethyl-N-methylaconitine; Japaconitine A; Japaconitine B
Catalogue No.: BP0935
Cas No.: 2752-64-9
Formula: C₃₃H₄₅NO₁₁
Mol Weight: 631.719
Botanical Source: Alkaloid from Aconitum manschuricum and many other Aconitum spp. (Ranunculaceae)
Physical Description: White powder
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, up to kilograms
Inquire for bulk scale.

Descriptions:
Mesaconitine increases the [Ca2+]i level in endothelial cells by influx of Ca2+ from extracellular spaces, suggests that mesaconitine-induced Ca2+ influx and activation of nitric-oxide synthase in endothelial cells and, thus, induced vasorelaxation in rat aorta.[1]
Mesaconitine is highly toxic, can inhibit Efflux transporters, including P-glycoprotein (P-gp), breast cancer resistance protein (BCRP), and multidrug resistance-associated protein isoform 2 (MRP2).[2]
Mesaconitine has antinociceptive activity, has inhibition of stimulus-triggered and spontaneous epileptiform activity in rat hippocampal slices.[3,4]
Mesaconitine has antiinflammatory activity, can inhibit carrageenin-induced hind-paw edema in sham-operated mice as well as adrenalectomized mice, it do not affect the biosynthesis of the prostaglandins. [5]


References:
[1] Mitamura M, Horie S, Sakaguchi M, et al. Eur J Pharmacol, 2013, 436(3):217-25.
[2] Ling Y, Yang X, Zhen Y, et al. Toxicol Lett, 2013, 216(2-3):86-99.
[3] Suzuki Y, Oyama T, Ishige A, et al. Planta Med, 1994, 60(5):391-4.
[4] Ameri A. Eur J Pharmacol, 1998, 342(2-3):183-91.
[5] Hiroshi H, Hiroshi T, Mitsuo F, et al. Eur J Pharmacol, 1982, 82(1-2):65-71.
[6] Zhou J, Ling Y E, Tang L, et al. China Journal of Traditional Chinese Medicine & Pharmacy, 2013, 38(10):1521-5.

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

Introduction/Overview

Mesaconitine (CAS No.: 2752-64-9), as one of the main active alkaloids in Aconitum species, has long attracted attention in the field of natural product pharmacology due to its unique chemical structure and significant pharmacological activity. Aconite plants have been widely used in traditional Chinese medicine since ancient times, especially showing good efficacy in pain relief, anti-inflammation, and cardiovascular diseases. As an isomer of neo-aconitine, Chinese aconitine has a complex molecular structure and multi-target action characteristics. In recent years, with the development of modern pharmacological technologies, its mechanism of action and potential clinical application value have gradually been revealed.

This paper aims to systematically review the chemical structure and physicochemical properties, plant origin, and extraction methods of Aconitine, explore its pharmacological activity and mechanism of action in depth, analyze its pharmacokinetic characteristics in combination with druggable parameters, and finally look ahead to its clinical application prospects, providing a theoretical foundation and practical guidance for subsequent related research.

Chemical structure and physicochemical properties

Aconitine is a dihydroditerpene alkaloid with the molecular formula C36H51NO11 and a molecular weight of 631.7190. Its structure contains multiple ester groups and ether bonds, featuring high polarity and complex three-dimensional conformations. The LogP value of Aconitine is 1.5884, indicating moderate lipid solubility, which facilitates cell membrane penetration without being overly hydrophobic. Its topological pole surface area (TPSA) is 153.45 Ų, showing strong polarity that may affect its bioavailability and blood-brain barrier penetration ability.

Water solubility is 0.1765 mg/mL, classifying it as a low-solubility compound, suggesting that solubility enhancement strategies should be considered in formulation development. The blood-brain barrier has low permeability, which may limit direct action on the central nervous system, but also reduces the risk of central toxicity. The hERG channel inhibition test was negative, indicating a low risk of cardiac toxicity in aconitine. The Ames test result was 0.6, indicating low mutagenicity and a solid safety foundation.

Plant Origins and Extraction Methods

Mesoconitum is mainly found in Aconitum spp., especially abundant in Aconitum carmichaelii and its varieties. Aconite plants are widely distributed in China, Japan, and other parts of East Asia, and have long been used as traditional Chinese medicinal materials. The rhizome is the main medicinal part and contains various alkaloids, among which aconitine is one of the important active components.

Common extraction methods for aconitine include solvent extraction, acid-base separation, and column chromatography purification. Traditional processes mostly use ethanol or methanol as solvents, extracting crude extracts through reflux, followed by acid-base extraction to separate alkaline alkaloids. Further purification mostly uses silica gel column chromatography, countercurrent chromatography, or high-performance liquid chromatography (HPLC) techniques to ensure the purity and activity of aconitine. In recent years, green extraction technologies such as ultrasound-assisted extraction and microwave-assisted extraction have also been applied to improve extraction efficiency and reduce environmental pollution.

Pharmacological activity research

Aconitine has various pharmacological activities, with its analgesic effect being the most prominent. Its analgesic effects have been validated in various animal models, including models of heat pain, mechanical pain, and inflammatory pain. Compared with traditional opioid analgesics, aconitine shows stronger analgesic efficacy within a certain dosage range and has relatively fewer side effects.

In addition, aconitine also exhibits multiple pharmacological effects, including anti-inflammatory, antiarrhythmic, and neuroprotective effects. Its anti-inflammatory effects mainly work by inhibiting the release of inflammatory mediators and regulating immune cell function. In cardiovascular matters, aconitine can regulate the electrophysiological properties of myocardial cells and has potential antiarrhythmic effects. Neuroprotective effects are related to its regulation of neurotransmitters and antioxidant capacity.

Mechanism of action and molecular targets

The pharmacological mechanism of aconitine is complex, involving multiple molecular targets, especially in the field of analgesia, showing coordinated regulation of multiple targets. Its main targets include:

• TRPV1 (Transient Receptor Potential Vanillic Acid Subtype 1): Mesoconitine can modulate TRPV1 channel activity, affect pain signal transmission, and exert analgesic effects.
• CNR1 (Cannabinoid Receptor 1): By activating CNR1, aconitine regulates neurotransmitter release, relieving pain and inflammation.
• OPRD1, OPRM1, OPRK1 (δ, μ, κ opioid receptors): The interaction between aconitine and opioid receptors enhances its analgesic effect and may reduce tolerance and dependence on traditional opioids.
• PTGS1 and PTGS2 (cyclooxygenases 1 and 2): Inhibit the activity of these two enzymes, reduce prostaglandin synthesis, and exert anti-inflammatory and analgesic effects.
• TRPA1 (transient receptor potential vanillin subtype A1): regulates TRPA1 channels and participates in the regulation of inflammatory pain.
• SLC6A4 (serotonin transporter): affects serotonin reuptake, regulates mood, and pain perception.
• DRD2 (Dopamine D2 receptor): Involved in pain relief and neuromodulation via dopamine signaling pathways.

The multiple synergistic effects of these targets give mesoconitine unique advantages in pain relief and the treatment of related diseases.

Druggability evaluation and pharmacokinetics

Druggability evaluation is a crucial step in new drug development. The physicochemical properties of aconitine indicate that it has certain medicinal potential, but there are also some challenges. It has a large molecular weight, strong polarity, and low water solubility, which may affect oral bioavailability. The blood-brain barrier has low permeability, limiting its direct effect on the central nervous system, but it helps reduce central toxicity.

The hERG channel inhibition test was negative, indicating a low risk of cardiotoxicity and facilitating safety evaluation. Ames test results show that it has low mutagenicity and meets safety requirements. Pharmacokinetic studies show that aconitine metabolizes rapidly in the body, mainly through hepatic enzyme systems, and metabolites require further identification. Its half-life is moderate, making it suitable for multiple doses to maintain efficacy.

Future druggability optimization can improve bioavailability and targeting through structural modification, nanocarrier encapsulation, and sustained-release formulation development, thereby reducing potential toxic side effects.

Prospects and outlooks for clinical applications

As a natural product with multi-target effects, Chinese aconitine demonstrates broad clinical application potential. Its remarkable analgesic effect makes it highly valuable in the treatment of chronic pain, neuropathic pain, and inflammatory pain. Compared to traditional opioids, aconitine may reduce the risk of resistance and dependence, offering new analgesic treatment options.

In addition, its anti-inflammatory, antiarrhythmic, and neuroprotective effects offer new ideas for the treatment of cardiovascular and neurodegenerative diseases. With the advancement of pharmaceutical formulation technology, the pharmacokinetic shortcomings of Chinese aconitine are expected to be improved, further promoting its clinical translation.

Future research should focus on in-depth analysis of its mechanism of action, systematic improvement of safety evaluation, and the implementation of clinical trials. Multidisciplinary integration will promote the transition from laboratory research to clinical application, driving innovation in natural product drug development.

Conclusion

As an important active ingredient in Aconitum plants, Chinese aconitine shows broad application prospects in analgesic and related disease treatments due to its unique chemical structure and multi-target pharmacological effects. Its druggability parameters provide a solid safety foundation, but there are challenges in bioavailability and pharmacokinetics. In the future, structural optimization and the application of advanced formulation technologies are expected to overcome these limitations and promote clinical translation.

In summary, Chinese aconitine not only enriches the research content of natural product pharmacology but also provides valuable resources for the development of novel analgesic drugs. We look forward to more in-depth basic and clinical research to promote its safe and effective clinical use, achieving the successful transformation of natural products into modern medicines.