Aconitine – the queen of poison

Aconitine (Fig. 1) is a C19-norditerpenoid ester alkaloid, with the presence of acetylester and benzoylester group in the position C8 and C14 of the diterpenoid skeleton, respectively. Aconitine is present species of the genus Aconitum (e.g. monkshood), Delphinium (e.g. larkspur) and Consolida. These three genus belong to the Ranunculaceae family, comprising more than 250 species known toxic to humans. Apart from aconitine, plants of this family produce different alkaloids. E.g., genus Aconitum produces nine different alkaloids where aconitine is the most relevant explaining the toxicity of this plant.

The toxin is present in all parts of the plant but at different concentrations. The content depends on the species, season and environmental conditions. As general criteria, alkaloids are distributed in the plant as it follows: roots > flowers > leaves > stems. The alkaloids content of Aconitum is in the range of 0,4-2% fresh weight. The content of aconitine in different Aconitum species is in the range of 17- 4846 µg g^-1, being the highest concentration found in Aconitum pendulum.

Aconitine binds with sodium channels, changing the conformation to an activated state and therefore, prolonging depolarization and causing multiple toxic effects. The symptoms of acute intoxications show a combination of motor (muscle weakness, dizziness), cardiovascular (arrhythmias, hypotension) and gastrointestinal (vomiting, diarrhea) features. A dosis of 0.2 mg aconitine leads to severe intoxication, while dosis above 5 mg are letal for humans. Symptoms may be present about 15 minutes after oral exposure.

The interest in this alkaloid is derived from the use of Aconitum in Chinese traditional medicine from over 2000 years. The root is processed to produce “Fuzi”, which presents reduced toxicity and it is widely used as analgesic and anti-inflammatory. However, there are many cases of intoxication, or even death, after treatment with Fuzi. Unfortunately, there is still a lack of knowledge about the environmental implications of the intensive production of this plant. The high water solubility (629 mg/l) and log K_ow of aconitine (0,13) suggest that this toxin might have implication on water quality.

SMILES: CCN1CC2(C(CC(C34C2C(C(C31)C5(C6C4CC(C6OC(=O)C7=CC=CC=C7)(C(C5O)OC)O)OC(=O)C)OC)OC)O)COC

CAS: 302-27-2

References 

• Barceloux, D. G. (2008). Medical toxicology of natural substances: foods, fungi, medicinal herbs, plants, and venomous animals. John Wiley & Sons.
• Bicker, W., Monticelli, F., Bauer, A., Roider, G., & Keller, T. (2013). Quantification of aconitine in post‐mortem specimens by validated liquid chromatography‐tandem mass spectrometry method: Three case reports on fatal ‘monkshood’ poisoning. Drug testing and analysis, 5(9-10), 753-762.
• He, F., Wang, C. J., Xie, Y., Cheng, C. S., Liu, Z. Q., Liu, L., & Zhou, H. (2017). Simultaneous quantification of nine aconitum alkaloids in Aconiti Lateralis Radix Praeparata and related products using UHPLC–QQQ–MS/MS. Scientific reports, 7(1), 13023.
• Wang, Z., Wen, J., Xing, J., & He, Y. (2006). Quantitative determination of diterpenoid alkaloids in four species of Aconitum by HPLC. Journal of pharmaceutical and biomedical analysis, 40(4), 1031-1034.

Figures: 

• http://prunepicker.blogspot.dk
• Wikipedia, The Free Encyclopedia. https://en.wikipedia.org/wiki/ (accessed January 14, 2018).