Galanthamine – onions make you cry, others could make you die

Photos (left to right): snowdrops, daffodils, daffodils’ bulbs

The toxin belongs to the Amaryllidaceae family of alkaloids, acting as an acetylcholinesterase inhibitor (AChEI). This group of chemicals prevent the enzyme acetylcholinesterase to break down the neurotransmitter acetylcholine, leading to the accumulation of the latter in the central and peripheral nervous systems (1). In such environment, nicotinic and muscarinic receptors are hyperstimulated and the neurotransmission is disrupted. That is the reason why acetylcholinesterase inhibitors are considered toxins and are also applied as drugs.

Left: acetylcholinesterase inhibitors. Right: Structure of Galanthamine. Click image for 3D structure

The toxin is found in all parts of the plant, however, the main risk is when people mistake their bulbs for onions (2). Consumption of leaves and stems can also happen by livestock or children. If eaten, the symptoms can vary from nausea, vomiting and diarrhea to dizziness. No further treatment is usually required other than rinse of the mouth and hydration; if symptoms persist or get worse, medical treatment is needed (3).

This toxin has been extensively used to treat Alzheimer’s disease since the 90’s. The drug can be extracted from the plant, as well as produced synthetically (4). The disease is characterized by reduced synthesis of the neurotransmitter acetylcholine; galanthamine counteract the effects of the disease, allowing acetylcholine to survive for a longer time.

In addition, a complex galanthamine/atropine can be used as an antidote for nerve agents (5). They compete for inhibiting the enzyme acetylcholinesterase with irreversible inhibitors such as soman, sarin, or paraoxon. If administered before or soon after acute exposure to lethal doses of those agents it can counteract their toxicity.

SMILES: CN1CCC23C=CC(CC2OC4=C(C=CC(=C34)C1)OC)O

References:

1. Čolović MB, Krstić DZ, Lazarević-Pašti TD, Bondžić AM, Vasić VM. Acetylcholinesterase Inhibitors: Pharmacology and Toxicology. Curr Neuropharmacol. 2013 May;11(3):315–35.
2. Supermarkets told to keep daffodils away from fruit and vegetables due to poisoning risk [Internet]. International Business Times UK. 2015. Available from: http://www.ibtimes.co.uk/supermarkets-told-keep-daffodils-away-fruit-vegetables-due-poisoning-risk-1487034
3. Poison control: Daffodils. Available from: https://www.poison.org/articles/2015-mar/daffodils
4. Marco L, do Carmo Carreiras M. Galanthamine, a natural product for the treatment of Alzheimer’s disease. Recent Patents CNS Drug Discov. 2006 Jan;1(1):105–11.
5. Albuquerque EX, Pereira EFR, Aracava Y, Fawcett WP, Oliveira M, Randall WR, et al. Effective countermeasure against poisoning by organophosphorus insecticides and nerve agents. Proc Natl Acad Sci. 2006 Aug 29;103(35):13220–5.

Photos:

• Snowdrop: https://www.first-nature.com/flowers/galanthus-nivalis.php
• Daffodils: https://www.quickcrop.ie/blog/2017/08/planting-bulbs/
• Daffodils’ bulbs: http://www.ibtimes.co.uk/supermarkets-told-keep-daffodils-away-fruit-vegetables-due-poisoning-risk-1487034
• Acetylcholinesterase inhibitors: https://elitenootropics.com/cholinergic-nootropics/
• Galanthamine structure: http://www.chemspider.com/Chemical-Structure.9272.html