*What sets galantamine apart from other cholinergic nootropics is its two-pronged action resulting in increased acetylcholine and activation of nicotinic acetylcholine receptors. *
Galantamine belongs to the class of drugs known as cholinesterase inhibitors. Cholinesterases are enzymes responsible for the breakdown of acetylcholine, a neurotransmitter involved in learning and memory. Inhibiting cholinesterases thus increases synaptic acetylcholine and cholinergic neurotransmission in the brain.
Galatamine is a naturally present alkaloid. It differs in this respect compared with other cholinesterase inhibitors like Donepzil which are lab synthesized. (Though galantamine can be produced from natural sources, the total synthesis of galantamine has been patented and is now used on an industrial scale.)
Acetylcholinesterase inhibitors are used medically for the treatment of:
- Myasthenia gravis
- Postural tachycardia syndrome
- Antidote to anticholinergic poisoning
- Reverse the effects of muscle relaxants
- Alzheimer’s disease, Lewy Body Dementia, and Parkinson’s disease
- To increase lucid dreaming
- Cognitive impairments arising from schizophrenia
- Autism (to increase the percentage of time spent in REM sleep)
Galantamine and Nicotinic Acetylcholine Receptors
One study tested the effects of galantamine on dopamine cell firing rate in rodents. They found that at low doses, galantamine increased firing rate of dopaminergic cells in the ventral tegmental area. Galantamine only inhibits acetylcholinesterases (AchE) at high doses, so this effect on dopamine activity cannot be attributed to AchE inhibition. The effect of galantamine on dopamine was prevented by the nicotinic acetylcholine receptor antagonist mecamylamine, but not the muscarinic acetylcholine antagonist scopolamine. This strongly implied that galantamine increases dopamine cell firing rate by activating or potentiating nicotinic acetylcholine receptors.
Galantamine’s nootropic effects stem from its activity at nicotinic acetylcholine receptors. These receptors play an important role learning and memory. These receptors are also reduced in number or activity in patients with neurodegenerative disease and schizophrenia. The idea that schizophrenic patients might have hypofunctional nicotinic receptors came from the recognition that tobacco smoking is highly prevalent among schizophrenics. Schizophrenics tend to smoke more cigarettes, inhale more deeply. Nicotine and the other psychoactive alkaloids in tobacco may also ameliorate some of the cognitive symptoms of schizophrenia. Since galatamine aslo activates nicotinic acetylcholine receptors, it is used clinically to treat schizophrenia-induced cognitive impairment.
Even in healthy subjects, activating nicotinic receptors (e.g. with galantamine or nicotine) tends to improve working memory, cognitive function, arousal and mood. One researcher claims that nicotine is that only substance that reliably enhances cognition in health adults.
Specifically, galantamine is an allosteric modulator of the following subtypes of nicotinic acetylcholine receptors: a2b4, a7/5-HT3, a3b4, and a6b4.
Galantamine vs Other Nootropic Cholinergics
Galantamine has a number of advantages over other cholinergic drugs and nutraceuticals.
- Galantamine is a reversible and relatively weak inhibitor of cholinesterases. This “gentle” inhibition is favorable because excessive inhibition results in SLUDGE syndrome.
- Galatantamine potentiates nicotinic acetylcholine receptors. This activity is central to its nootropic effects. Nicotine also enhances cognition and working memory by activating the receptors named after it. Those who are concerned about the deleterious health effects of nicotine can try using galantamine instead.
- Unlike huperzine A, galantamine is not an NMDA-type glutamate receptor antagonist.
- Galantamine enhances dopamine release in the prefrontal cortex and may be useful in the treatment of schizophrenia.
Galantamine is superior to huperzine A, another cholinergic nootropic. Huperzine A is extremely potent and is therefore dosed in the microgram range. This increased potency is a double-edged sword because Huperzine A has a greater toxicity.
Excessive acetylcholinesterase inhibition results in SLUDGE syndrome. SLUDGE is often caused by organophosphates, which are also acetylcholinesterase inhibitors A. Huperzine A is also an NMDA-type glutamate receptor blocker which can theoretically impair long-term potentiation.
Subjective Effects of Galantamine
Galantamine is stimulating, though it is not a psychostimulant like amphetamines. Galantamine improves working memory, also known as short-term memory. This effect can facilitate problem-solving, since the amount of information the brain can “hold” at a time can be a limiting factor. Working memory is strongly linked to IQ.
Galantamine also improves executive function, concentration and how rewarding a task is perceived to be (“task salience”). This effect is attributed to galantamine’s enhancement of dopamine release in the prefrontal cortex. In addition to galantamine, nicotine itself stimulates nicotinic acetylcholine receptors in the ventral tegmental area (VTA), activating midbrain dopaminergic neurons.
Side Effects of Galantamine
Galantamine’s side effect profile is similar to other acetylcholinesterase inhibitors. Side effects arise from increasing the activity of the parasympathetic (rest and digest) arm of the nervous system. The sympathetic and parasympathetic nervous systems are constantly opposing each other. Sympathetic tone increases heart rate, heart contractility, constricts blood vessels and increases sweating. Galantamine, as a parasympathomimetic, has the opposite effects.
Side effects of galantamine include:
- Abdominal discomfort and pain
- Diminished appetite
- Yellowing of the skin
- Rapid weight loss
- Bradycardia (slowed heart rate)
- Hypotension (decreased blood pressure)
- GI tract hypermotility
- Reduced intraocular pressure
- SLUDGE syndrome - Salivation (increased activity of salivary glands)
- Lacrimation (increased lacrimation/tearing)
- Urination (relaxation of the internal sphincter muscle of urethra)
- Gastrointestinal upset
- Emesis (vomiting)
- Miosis (stimulation of pupillary constrictor muscles)
Muscle spasm (stimulation of skeletal muscle)