Strychnine - a highly toxic indole alkaloid – University of Copenhagen

NaToxAq > Toxin of the week > Strychnine

05 February 2018

Strychnine - a highly toxic indole alkaloid

Natural toxin

Strychnine is a highly poisonous natural compound well known to chemists as well as to the broader public.

The toxin has been used as a rodenticide for more than a century and it has been involved in accidental poisonings in humans and animals. In small amounts, strychnine is known to be added to “street drugs,” such as LSD, heroin, cocaine, and others (3).

The structure of strychnine was determined by Woodward in 1948. The toxin is most commonly derived from the seeds of Strychnos nux-vomica, a native tree of South India, and a related climbing shrub, Strychnos ignatii, native to the Philippines called St. Ignatius’ bean (Figure 1) (1).

Figure 1. Strychnos nux-vomica (left) and Strychnos ignatii (right).

Strychnine is a terpene indole alkaloid belonging to the Strychnos family of alkaloids. Usually it is marketed as strychnine sulfate. It is an odorless base (pKa = 8.26) forming colorless or white crystals that melt at 275–285°C. While it is barely soluble in water, its hydrochloride and nitric acid salts are water soluble. Under abiotic conditions, strychnine is a relatively stable compound. It is photostable and does not hydrolyze at pH 5-9 (2).

The LD50 of strychnine for most species lies in the range of 0.4-3 mg/kg body weight. Following the ingestion of strychnine, symptoms of poisoning usually appear within 15–60 min (3). Strychnine blocks cholinergic receptors in skeletal muscles. Excessive doses can lead to paralysis of respiratory muscles causing asphyxia and death. There are three main ways that strychnine can enter the body: inhalation, ingestion, and through broken skin (1).

Figure 2. Chemical structure of strychnine. Click image for 3D model

Its easy isolation led to strychnine being a widely used pest control agent in the past and it is still in use in some countries. Due to strychnine’s high persistence in the environment and lack of an adequate antidote, use of strychnine should be strictly limited. In case of above-ground uses, present of the toxin in the environment may pose serious threat to the animals and humans. In Australia, strychnine can only be used with the approval of the Risk Assessor and Department of Water (5).

SMILES: O=C7N2c1ccccc1[C@@]64[C@@H]2[C@@H]3[C@@H](OC/C=C5\[C@@H]3C[C@@H]6N(CC4)C5)C7

References:

  1. Jane H. Bock and David O. Norris, Chapter 1 - Introduction to Forensic Plant Science, In Forensic Plant Science, Academic Press, San Diego, 2016, Pages 1-22, ISBN 9780128014752, https://doi.org/10.1016/B978-0-12-801475-2.00001-4.
  2. István Ujváry, Chapter 3 - Pest Control Agents from Natural Products, In Hayes' Handbook of Pesticide Toxicology (Third Edition), edited by Robert Krieger,, Academic Press, New York, 2010, Pages 119-229, ISBN 9780123743671,
  3. Ramesh C. Gupta, Michelle A. Lasher, Robin B. Doss and Dejan Milatovic, Chapter 17 - Skeletal muscle toxicity biomarkers, In Biomarkers in Toxicology, Academic Press, Boston, 2014, Pages 291-308, ISBN 9780124046306.
  4. Water quality protection note 96, November 2009. Pest animal management in public drinking water source areas. Government of Western Australia. Department of Water.

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