If Only Galantamine Could Talk

Galantamine—A Molecule with a Past

If Only Galantamine Could Talk …
From ancient Greece to the Soviet Union—an improbable but
probably true story, with a gap of only 28 centuries
By Will Block

History is more or less bunk.
— Henry Ford

Odysseus resisting Circe
n that usually misquoted comment, Ford went on to say, “It’s tradition. We don’t want tradition. We want to live in the present, and the only history that is worth a tinker’s damn is the history we make today.” Ford was a man driven to get results—he also said, “Whether you believe you can do a thing or not, you are right.” Whether you agree with him or not, his take on history is thought-provoking. Perhaps the best way to look at history is to try to extract from it whatever lessons are useful in our efforts to make history today.

The trouble is, historical knowledge is not always easy to come by. Take, for example, the nutrient galantamine, a chemical compound derived from certain flowers. To anyone with Alzheimer’s disease, or at risk for it, galantamine could be just about the most precious substance in the world, because it’s the most potent and versatile of all anti-Alzheimer’s agents. Thus the history of its medicinal use may be of more than passing interest.

Of course, galantamine as a chemical compound was not known until modern times, but the medicinal effects obtained from certain flowering plants that are now known to contain it, notably the snowdrop, have long been known. (The snowdrop, a pretty white flower, occurs as several species of the genus Galanthus. For a list of the best-known galantamine plants, see the sidebar “A Bit of Botany.”)

A Bit of Botany

The plant sources of galantamine are found in the family Amaryllidaceae, which consists of herbaceous plants that have strap-shaped leaves and clusters of flowers (rarely one flower) atop a leafless stem. Among the genera in this family are four that include the principal galantamine-containing species:

  • Galanthus (G. nivalis and G. woronowii) — snowdrop
  • Leucojum (L. aestivum) — snowflake
  • Lycoris (L. radiata) — spider lily
  • Narcissus (N. pseudonarcissus L.) — daffodil

As their common names suggest, the Galanthus and Leucojum species look very similar, and they are often confused. Although Galanthus was the traditional source of galantamine, the compound is now obtained primarily from Narcissus and Leucojum species, as well as being manufactured synthetically.

Of Magic Spells and Potions …

Galantamine has a recorded history that is, shall we say, unconventional and fragmentary. The substance first showed up—according to an intriguing hypothesis advanced by two scholars in 1983—around 850 B.C., in Homer’s Odyssey.1 His epic poem recounted the ten-year period of heroic adventures experienced by King Odysseus of Ithaca (a Greek island) on his zigzag voyage home following the Trojan War, which was fought around 1200 B.C.

In one of the stories, Odysseus’s men were bewitched by the goddess Circe, who cast a spell that made them forget about their mission (which was to return to Ithaca). Worse than that, she turned them into swine. The potion she used could have been made from jimsonweed (Datura stramonium), which contains atropine, an alkaloid that can induce amnesia and bizarre hallucinations. Jimsonweed is known to have been native to that region, and the people of that time knew of its neurotoxic properties.

To break the spell on his men and restore their memory, Odysseus used a potion of his own, made from a flower that Homer called moly; it was a gift to Odysseus from Hermes, the messenger of the gods, when they met in a forest on the way to Circe’s palace. Based on Homer’s description of it and the pharmacological action he attributed to it, that flower is now believed to have been Galanthus nivalis, the common snowdrop, which was also native to that region. The snowdrop is an antidote to jimsonweed, because galantamine is an antidote to atropine.

… That Could Have Been More or Less Real

If all this still sounds far-fetched, bear in mind that many ancient legends are now believed to have been based on historical facts—with liberal embellishments, such as gods and goddesses and monsters and magic potions, for literary purposes. (Have you never spiced up a story for effect?) By tuning out the embellishments and exaggerations, and by focusing on what was actually possible according to the laws of science and what we know about the natural world at the time and place in question, modern scholars have been remarkably successful in explaining the probable factual bases for many legends, including Biblical stories, that once seemed beyond the realm of reason.

The Looong Silence

From Homer’s time, fast-forward a mere 28 centuries to the next recorded use of galantamine, around 1950 in Bulgaria, when the Cold War was heating up (so to speak). Oops! What happened to galantamine in the interim? No one knows. Part of the problem is that the use of galantamine in folk medicine seems to have been centered (not surprisingly) in the region to which snowdrops are native, namely, Southeast Europe and Southwest Asia (thus including the Caucasus).* Apart from the fact that this region was comprised mostly of republics of the Soviet Union, which remained locked behind the Iron Curtain for four more decades, it has traditionally been a meager source of historical documentation.

*To refresh your memory, the Caucasus is a mountainous region between the Black Sea and the Caspian Sea that includes southwest Russia, Georgia, Azerbaijan, and Armenia; it forms part of the traditional boundary between Europe and Asia.

Western scholars (ethnobotanists and ethnopharmacologists) have tried, without notable success, to find out what led up to the modern rediscovery, as it were, of galantamine in Bulgaria.2 To add to their frustration, the abundant botanical and medical literature of Western Europe in the Middle Ages appears to contain virtually no references to medicinal uses for the plants from which galantamine is derived. Curiously, the fountainhead from which these books sprang, the magisterial De Materia Medica, written in the first century A.D. by the Greek physician and botanist Dioscorides, did describe the moly plant. There was no reference to its epic use, however, perhaps because Dioscorides was a scientist at heart and eschewed ideas that were not supported by hard evidence.

The Exciting 1950s in Bulgaria

So let’s make the best of this and recap what happened in the 1950s and thereafter. It all seems to have begun when a Bulgarian pharmacologist noticed people rubbing their foreheads with snowdrops (probably the leaves or the bulbs, not the flowers, because it’s the leaves and bulbs that contain galantamine) to ease pain.2 This had probably been a common practice for a long time, but his observation brought it to scientists’ attention.

That led to the publication, in 1951, of a paper by two Russians, who gave the first pharmacological description of galantamine.3 They showed that galantamine acts as an acetylcholinesterase inhibitor, i.e., a molecule that helps maintain normal levels of the neurotransmitter acetylcholine in the brain, by inhibiting the action of the enzyme that attacks it. Acetylcholinesterase inhibitors have become the dominant form of therapy for Alzheimer’s disease, which is characterized by deficits in cholinergic (acetylcholine-based) function.

We now know that galantamine—unlike other anti-Alzheimer’s agents—has an additional mode of cholinergic action that gives it a distinct edge in efficacy, especially in the long term. That mode is its modulation of nicotinic acetylcholine receptors in the brain—a very important preservation mechanism that we won’t go into right now.

The following year, 1952, saw publication of a paper describing the first isolation and identification of galantamine, an alkaloid, as a unique chemical compound. (Determining the molecular structure of a natural substance is essential for enabling chemists to devise strategies for synthesizing it from scratch.) Much research on galantamine by Russian and Bulgarian scientists followed during the 1950s and beyond. In 1958 it was commercialized in Bulgaria under the trade name Nivalin®.

Galantamine Used to Treat Polio

In medical practice throughout Eastern Europe, the compound came to be used for the alleviation of neuromuscular ailments, such as neuritis and neuralgia.4 It is known to be a muscle stimulant (it counteracts the effects of the powerful muscle relaxant curare, for example). Evidence also shows that galantamine was used for treating neurological conditions such as post-polio paralysis and myasthenia gravis.1 Indications that the compound enhances neurotransmission in the brain led to its being used to treat poliomyelitis, and this has been its primary use in Eastern Europe for the last half-century.2

Galanthus nivalis, the common snowdrop
Commercialization of Galantamine for Alzheimer’s

It was not until the 1980s that neurological researchers in Western Europe began looking seriously at galantamine, owing to the ease with which it crosses the blood-brain barrier (an essential attribute for any compound that is to affect the central nervous system) and its beneficial effects on cholinergic function. Preclinical investigations of galantamine for use in Alzheimer’s disease ensued, and full-scale clinical trials were conducted in the 1990s. Galantamine was first used (as Nivalin) for the treatment of Alzheimer’s in 1996, and in that year, the first patent on a synthetic process for the compound was issued to an Austrian company, Sanochemia Pharmazeutika.

Subsequent commercialization of galantamine was undertaken by a Belgian company, Janssen Pharmaceutica (a subsidiary of Johnson & Johnson), and a British company, Shire Pharmaceuticals Group. In 2000 the compound emerged under the new trade name Reminyl®, and in 2001 the FDA approved its use for the treatment of mild to moderate cases of Alzheimer’s disease in the United States. This action bore witness to the safety and efficacy of a substance that, in its natural form, had been used as a supplement for decades … probably centuries … perhaps millennia. And it continues to be offered to the public as what it still is: a nutritional supplement.

Galantamine Is the Real Deal

Well, that’s the history of galantamine in a nutshell. You, Dear Reader, will have to decide whether you think it’s “more or less bunk.” One thing is for sure: galantamine itself is not bunk. It’s the real deal—tried, tested, and proved for its purpose. (Potential new uses for galantamine occasionally surface, however—see below.) For those who wish to preserve and protect their memory and other cognitive functions from the insidious encroachments of age, galantamine may be just what the gods ordered.


  1. Plaitakis A, Duvoisin RC. Homer’s moly identified as Galanthus nivalis L.: physiologic antidote to stramonium poisoning. Clin Neuropharmacol 1983;6:1-5.
  2. Heinrich M, Teoh HL. Galanthamine from snowdrop—the development of a modern drug against Alzheimer’s disease from local Caucasian knowledge. J Ethnopharmacol 2004;92:147-62.
  3. Mashkovsky MD, Kruglikova-Lvova RP. On the pharmacology of the new alkaloid galantamine. Farmakologia Toxicologia (Moscow) 1951;14:27-30 (in Russian).
  4. Venturi VM, Piccinin GL, Taddei I. Pharmacognostic study of self-sown Galanthus nivalis (var. gracilis) in Italy. Boll Soc Ital Biol Sper 1965 Jun 15; 41(11):593-7.

Galantamine for Adult Autism

Whereas Alzheimer’s is a disease of aging, autism begins early—the symptoms always appear before the age of 3, and they usually last for life. The hallmarks of autistic individuals, most of whom have subnormal intelligence, are their drastically impaired communication and socialization skills, their compulsive and ritualistic behaviors, and their obsessive attachments to familiar objects. They typically prefer to be alone, are not affectionate, avoid eye contact, resist change, and are easily irritated. It’s a tragic existence, and very hard on the caregivers.

The cause of autism is unknown, but it is not poor parenting, as some have suspected. Various brain abnormalities can sometimes be seen, using noninvasive imaging techniques such as computed tomography (CT) or magnetic resonance imaging (MRI). No drugs seem to improve autism significantly. Some provide limited, temporary alleviation of certain symptoms, but they also have possible severe side effects.

Recently a physician in Maryland published case histories of the use of galantamine in three autistic adults: two black males, aged 21 and 32, and a white male aged 42.1 All three exhibited severely restricted communications, ranging from one- or two-word utterances (mainly “yes” or “no” responses that were not always appropriate to the question) to none at all. There were also behavioral problems, including chaotic and aggressive behavior.

When the physician treated these three men with galantamine, starting with a dose of 4 mg/day at bedtime and escalating it to 12 or 16 mg/day, their condition improved somewhat, with more (and more appropriate) verbalization in two cases and much less aggressive behavior in one case. In one case, galantamine had to be discontinued because of a rash; when the anti-Alzheimer’s drug donepezil was tried in its place, the patient’s verbal and behavioral problems became worse, not better, so it too was discontinued.

These results, while not dramatic, are interesting and encouraging because they suggest that galantamine may have a broader spectrum of action in the central nervous system than had been thought. The author speculated that galantamine may affect not just the cholinergic (acetylcholine-based) system of neurotransmission but also the serotonergic (serotonin-based) system. This idea requires further investigation.

  1. Hertzman M. Galantamine in the treatment of adult autism: a report of three clinical cases. Int J Psychiatry Med 2003;33:395-8.

Dual-Action Galantamine

Galantamine provides a heralded dual-mode action for boosting cholinergic function: it inhibits the enzyme acetylcholinesterase, thereby boosting brain levels of acetylcholine, and it modulates the brain's nicotinic receptors so as to maintain their function. The recommended daily serving ranges from a low of 4 to 8 mg of galantamine to begin with to a maximum of 24 mg, depending on the individual's response.

For an added measure of benefit, it is a good idea to take choline, the precursor molecule to acetylcholine, as well as pantothenic acid (vitamin B5), an important cofactor for choline. Thus it is possible to cover all bases in providing the means to enhance the levels and effectiveness of your acetylcholine.

Will Block is the publisher and editorial director of Life Enhancement magazine.

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