Snowdrops and chemical warfare aren’t two things you’d expect to mention in the same sentence. However, there’s a surprising link between the two thanks to a compound found in these winter flowers. This graphic looks at this compound and how it helps treat both Alzheimer’s disease and nerve agent poisoning.
Snowdrops are themselves poisonous. This is due to poisonous alkaloid compounds, which are particularly concentrated in their bulbs. Two key alkaloids found in snowdrops are lycorine and galantamine; both are also found in daffodils. Though not potent enough to kill, ingesting snowdrop or daffodil bulbs can lead to diarrhoea and vomiting. Daffodil stems or bulbs have occasionally been mistaken for food due to their proximity to vegetable aisles.
Galantamine is of particular interest when it comes to the medicinal effects of snowdrops. It’s difficult to isolate an appreciable amount of it from snowdrops, so later chemists isolated it from certain varieties of daffodils instead. Today it can also be produced synthetically. To understand how its medicinal uses, we first have to understand a little about a messenger molecule in our bodies: acetylcholine.
Acetylcholine is a chemical messenger which has functions in both the brain and the body. In the brain, it plays important roles in learning and memory. In the body, it’s responsible for triggering muscle contraction. After release from nerve endings, it binds to receptors in muscle tissue, making the muscle contract. After acetylcholine has passed on its message, an enzyme called acetylcholinesterase breaks it down. This helps to keep its levels in check.
Galantamine is an acetylcholinesterase inhibitor. This means that it latches on to acetylcholinesterase and stops it from breaking down acetylcholine. Usually, this wouldn’t be a good thing – but there are cases where it can be helpful.
There is currently no cure for Alzheimer’s disease, but patients can take drugs to treat its symptoms. Galantamine is one of these drugs. Alzheimer’s disease sufferers have lower levels of acetylcholine in their brains, linked to worsening symptoms. Galantamine’s ability to block the breakdown of acetylcholine increases its concentration. Though it has some side effects, this can mitigate some Alzheimer’s symptoms.
It’s galantamine’s ability to disable acetylcholinesterase that also leads to its use in treating (or even preventing) nerve agent poisoning. The class of nerve agents that galantamine is useful against is the G series, also known as organophosphates. These compounds include poisons such as tabun, sarin, and soman.
Organophosphates are also acetylcholinesterase inhibitors, stopping the breakdown of acetylcholine. Unlike galantamine, they’re very reluctant to let go of the enzyme once they’ve latched on. This causes acetylcholine to build up, leading to vomiting, breathing difficulties, and convulsions. Ultimately, death occurs due to respiratory failure.
It might seem odd that galantamine finds use as an antidote to organophosphate poisoning when they both seem to do the same thing. While the exact mechanisms aren’t completely clear, it seems that there are two factors which combine to allow galantamine to act as an antidote.
Firstly, galantamine is a reversible inhibitor of acetylcholinesterase. This means that it comes and goes from the enzyme, as opposed to organophosphates which latch on and don’t let go. As such, it can bind to the enzyme and block organophosphates from binding to it, but also falls off. This means that acetylcholinesterase can still break down some acetylcholine.
The second factor relates to another enzyme, butyrylcholinesterase. Organophosphates are keen to latch on to this enzyme too, but galantamine isn’t. This means that butyrylcholinesterase mops up the organophosphate molecules while galantamine denies them access to acetylcholinesterase.
Galantamine can be used as an antidote immediately after organophosphate poisoning, but can also be used preventatively before exposure. So far, this information is based on animal studies. As these have been successful to this point the compound may eventually progress to use as an antidote in humans. Even if it doesn’t, as the snowdrops bloom in your garden in the coming weeks you can marvel at this dainty plant’s medicinal potential!
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References & Further Reading
- Molecule of the month: Galanthamine – S Cotton
- Galanthus nivalis, Snowdrop – The Poison Garden
- The case of galantamine – repurposing and late blooming of a cholinergic drug – H A M Mucke
- Molecular and cellular actions of galantamine: treating organophosphate poisoning (£) – E F R Pereira and others
- Can galantamine act as an antidote for organophosphorus poisoning? – T H Indu and others
- Acetylcholinesterase – D Goodsell
- Drug treatments for Alzheimer’s disease – Alzheimer’s Society