Galantamine for Inflammation
Q I remember reading somewhere (probably in Life Enhancement) that galantamine can serve to reduce inflammation in the brain. Is that true and, if so, how does it do that?
DRAKE, Culver City, CA
A Galantamine affects the cholinergic nervous system in two ways: it is a natural selective and rapidly-
reversible acetylcholinesterase inhibitor (AChEI), and it also operates as an allosterically potentiating ligand (binder) of neuronal nicotinic receptors. Among the commonly used AChEIs, most of which are drugs, this later mechanism is unique to natural galantamine.
Research dating back to at least 2003 has shown that the cholinergic nervous system, acting via the vagus nerve, serves as one of our body’s natural anti-inflammatory mechanisms. As an example, it can help prevent excessive release of inflammatory cytokines in infection/?sepsis or autoimmune diseases, including rheumatoid arthritis.
In the same referenced study, the nicotinic acetylcholine receptor alpha7 subunit was identified as essential to the cholinergic anti-inflammatory effects. This receptor has been found to be activated by nicotine (as found in tobacco smoke). But due to nicotine’s addictive and other adverse effects—for example, it promotes angiogenesis and increases oxidative stress—there are very few people who are very enthusiastic about using it as an anti-inflammatory. However, Wang et al. suggest that “… it is now reasonable to consider the therapeutic potential for targeting the nicotinic acetylcholine receptor alpha7 subunit to inhibit TNF [tumor necrosis factor, a potent inflammatory cytokine], either by direct pharmacological approaches or through increasing activity in the vagus nerve.”
Durk Pearson & Sandy Shaw have called attention to the fact that acetylcholine acts as an agonist at the nicotinic and muscarinic acetylcholine receptors. While not selective for nicotinic receptors, a choline and vitamin B5 supplement can increase acetylcholine synthesis and release, which in turn can be expected to activate nicotinic acetylcholine receptors. As Durk & Sandy have repeatedly pointed out, choline and vitamin B5 supplements are quite safe to take and have no nasty side effects, as may occur with highly selective drugs such as selective COX-2 inhibitors, especially when used frequently. Moreover, COX-2 inhibitors are xenobiotic, and thus strangers to the body.
As mentioned, galantamine (naturally extracted from the snowdrop flower and bulb) acts as an agonist to nicotinic acetylcholine receptors and thus should enhance the cholinergic anti-inflammatory pathway. Anti-inflammatories such as those found in turmeric have been shown to protect against Alzheimer’s disease, as does galantamine. (See
“Maintain Your Brain the Durk Pearson & Sandy Shaw Way” in the May 2004 issue of Life Enhancement.)
- Wang H, Yu M, Ochani M, Amella CA, Tanovic M, Susarla S, Li JH, Wang H, Yang H, Ulloa L, Al-Abed Y, Czura CJ, Tracey KJ. Nicotinic acetylcholine receptor alpha7 subunit is an essential regulator of inflammation. Nature 2003 Jan 23;421(6921):384-8.
- Wurtman RJ. Choline metabolism as a basis for the selective vulnerability of cholinergic neurons. Trends Neurosci 1992 Apr;15(4):117-22.
- Ulus IH, Wurtman RJ. Choline increases acetylcholine release. Lancet 1987 Mar 14;1(8533):624.
- Lloyd GK, Williams M. Neuronal nicotinic acetylcholine receptors as novel drug targets. J Pharmacol Exp There 2000 Feb;292(2):461-7.