25 March 2019

Brucine – another neurotoxic alkaloid present in the Nux-vomica tree

Figure: Strychnos nux-vomica seeds (left) and nuts (right)

2,3-dimethoxystrychnidin-10-one, commonly known as brucine, is an alkaloid with similar structure than strychnine. It is produced by several plants but specially by the Strychnos nux-vomica tree, commonly known as the vomiting nut or the poison nut. Nux-vomica is translated to “nuts that causes vomits”. It was first discovered in the bark of this tree in 1819 by Pelletier and Caventou. The brucine content in seeds and bark of poison nut have been estimated to be 1.5 and 2-3%, respectively.

Molecular structure of Brucine. Click for interactive 3D model

Uses: Brucine presents several uses in the chemical industry and medicine. The part of the plant most used are the seeds, as contain the highest alkaloid content. In the industry is widely used as denaturant for alcohol and oils and as addition agent to lubricants. In medicine, it has several applications, serving as a tool for studying the glycine receptors or for stereospecific chemical syntheses. It has shown promising results as inhibitor of angiogenesis in carcinoma tumors, repressing carcinoma cell migration and metastasis. However, the main problem of this application is the toxicity towards the central nervous system. In the traditional medicine, nux-vomica is used as a remedy to alleviate physical and emotional distress, as well as an antioxidant. However, the use of this medicine must be taken with caution, as there is not clear agreement in the scientific community regarding the claimed beneficial effects.

Toxicity: There is a small margin between a therapeutic and toxic dose. Compared with the other alkaloids present in the plant, strychnine, it presents lower toxicity. The mechanism of action is acting as antagonist of glycine receptors, paralyzing the peripheral nerve endings and causing convulsions. A lethal dose of brucine in an adult is assumed to be a 1000 mg dose, being 1/10-1/50 of the lethal dose of strychnine. Some of the side effects or symptoms of brucine intoxication are related with the nervous system. These effects are for example stiff neck, cramps, anxiety, convulsions or vomiting.

Routes of exposure: There are several ways of intoxication but mainly is by ingestion of the seeds or bark of the vomiting nut. Brucine also emits toxic fumes and nitrous oxides when heated, being inhalation a pathway for workers in the chemical industry.

Formula: C23H26N2O4
Molecular weight: 394.471 g/mol
CAS number: 357-57-3
Canonical SMILES: COC1=C(C=C2C(=C1)C34CCN5C3CC6C7C4N2C(=O)CC7OCC=C6C5)OC