Snowdrops? Snowdrops!

Here in Holland spring is in the air. One of the first messengers is the snowdrop, a small spring flower that appears when the last snow is gone (Latin name Galanthus nivalis).

Galanthus nivalis
Galanthus nivalis

Oh, well you might think, snow drop…great…
But the little snowdrop is the producer of a great chemical compound called galanthamine.
Galanthamine is a (fasten your seatbelt) reversible cholinesterase inhibitor.

Most of you are familiar with the important neurotransmitter acetyl-choline (ACh). In the brain it is responsible for e.g. learning, memory and creativity. It is also the neurotransmitter making muscle contraction possible. When acetylcholine is released from the vesicles of the motor-neuron, it crosses the synaptic cleft and attaches to ACh receptors. Only when enough of these receptors are engaged, the electric impulse is transferred and spreads over the muscular membrane and makes the muscle contract. A pretty important substance I think.

Now the ACh does not stay attached on the receptor forever, but is again broken down into its two components acetyl and choline. This is done by the enzyme cholinesterase. These two components are transported back to where they came from (the motor-neuron) and there again resynthesized into ACh.

Galanthus nivalis
Galanthus nivalis

We learned to manipulate this process.
1. think about curare, the lethal poison on arrows of indigenous tribes of the Amazon (in as far they haven’t been the subject of genocide) which attaches to the ACh receptor much faster and stronger than the ACh does and blocks the effects of ACh. Result: the muscle can no longer contract and is paralyzed. Curare derivates are used to selectively relax muscles during major surgery.
2. Nerve gasses like Sarin or Soman, and many pesticides, inhibit the cholinesterase enzyme irreversibly and the ACh is no longer broken down and stays attached to the receptor. This leads to a continuous tetanic contraction of all muscles, also the heart muscle and breathing muscles, which leads to a gruesome but relatively fast death.

Back to the snowdrop and galanthamine. Galanthamine does the same thing as nerve gas, but is reversible. So it falls apart fast and works only for a short time, leading to a temporary increase of ACh activity. And that can be very useful in cases where ACh is too low, for example in Alzheimer, in myasthenia gravis, or in aging. Galanthamine also leads to an increased muscle tone and an improvement in muscle functioning. That is why it has been used as a ergogenic aid.

I bet you never thought about that when you saw the tiny snowdrop in spring….

Heinrich, M; Teoh, H.L: Galanthamine from snowdrop—the development of a modern drug against Alzheimer’s disease from local Caucasian knowledge; J Ethnopharmacology Vol.92, 2004, pg. 147–162.

Mucke, H.A.M: Principles of therapeutics of Galanthamine; Drugs of Today, Vol.33, No.4, 1997, pg.251-257.

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