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Galantamine ( Nivalin, Razadyne, Razadyne ER, Reminyl, Lycoremine ) is used for the treatment of cognitive decline in mild to moderate Alzheimer’s disease and various other memory impairments. It can also be produced synthetically.
Studies of usage in modern medicine began in the Soviet Union in the 1950s. Galantamine was isolated for the first time from bulbs of Galanthus nivalis (common snowdrop) by the Bulgarian chemist D. Paskov and his team in 1956.
In addition to uses in Alzheimer’s disease, galantamine has been used to treat myasthenia, myopathy, muscular dystrophy, and sensory and motor dysfunction associated with disorders of the central nervous system.
1 Uses in mythology
2 Medical uses
2.1 Alzheimer’s disease
2.2 Available forms
3 Side effects
7 Drug interactions
9.1 Organophosphate poisoning
9.4 Lucid Dreaming
11 External links
Uses in mythology
In Homer’s Odyssey the god Hermes gives Odysseus an herb with “a black root, but milklike flower” called “moly”, which Hermes claims will make Odysseus immune to the sorceress Circe ‘s drugs. It is believed that moly is the snowdrop Galanthus nivalis, which is a source of galantamine.
Galantamine Uses treatment of dementia caused by Alzheimer’s disease Precautions
give fluids – drug can cause dehydration, diarrhea, or vomiting
watch for slow heart rate and fainting
can cause bladder blockage
can cause seizures
can cause bleeding in stomach or intestines
do not combine with other sleep aid medications
do not combine alcohol use with this drug
people with chronic obstructive pulmonary disease should be cautious
people with sleep apnea should be cautious
donepezil and rivastigmine are comparable drugs
behavioral, physical, or social therapy may be useful
Galantamine is indicated for the treatment of mild to moderate vascular dementia and Alzheimer’s.
Alzheimer’s disease is characterized by the impairment of cholinergic function.
To reduce the prevalence of negative side effects associated with galantamine, such as nausea and vomiting, a dose-escalation scheme may be used.
The product is supplied in both a prescription form as well as an over the counter supplement in twice-a-day tablets, in once-a-day extended-release capsules, and in oral solution.
Galantamine’s side effect profile was similar to that of other cholinesterase inhibitors, with gastrointestinal symptoms being the most notable and most commonly observed. One study reports higher proportions of patients treated with galantamine experiencing nausea and vomiting as opposed to the placebo group.
The U.S. Food and Drug Administration (FDA) and international health authorities have published an alert of galantamine based on data from two studies during the treatment for mild cognitive impairment (MCI) ; higher mortality rates were seen in drug-treated patients.
Galantamine’s chemical structure contains a tertiary amine. At a neutral pH, this tertiary amine will often bond to a hydrogen, and appear mostly as an ammonium ion.
Galantamine is a potent allosteric potentiating ligand of human nicotinic acetylcholine receptors (nAChRs) α 4 β 2, α 3 β 4, and α 6 β 4, and chicken/mouse nAChRs α 7 / 5-HT 3 in certain areas of the brain. By inhibiting acetylcholinesterase, it increases the concentration and thereby action of acetylcholine in certain parts of the brain. Galantamine’s effects on nAChRs and complementary acetylcholinesterase inhibition make up a dual mechanism of action. It is hypothesized that this action might relieve some of the symptoms of Alzheimer’s.
Galantamine’s dual mechanism of action
Galantamine in its pure form is a white powder. The atomic resolution 3D structure of the complex of galantamine and its target, acetylcholinesterase, was determined by X-ray crystallography in 1999 (PDB code: 1DX6 ; see complex ).
Absorption of galantamine is rapid and complete and shows linear pharmacokinetics. It is well absorbed with absolute oral bioavailability between 80 and 100%. It has a terminal elimination half-life of seven hours. Peak effect of inhibiting acetylcholinesterase was achieved about one hour after a single oral dose of 8 mg in some healthy volunteers.
The coadministration of food delays the rate of galantamine absorption, but does not affect the extent of absorption.
Plasma protein binding of galantamine is about 18%, which is relatively low.
Approximately 75% of a dose of galantamine is metabolised in the liver. In vitro studies have shown that Hepatic CYP2D6 and CYP3A4 are involved in galantamine metabolism. Within 24 hours of intravenous or oral administration approximately 20% of a dose of galantamine will be excreted unreacted in the urine.
In humans, several metabolic pathways for galantamine exist.
Metabolic pathways of galantamine
For Razadyne ER, the once-a-day formulation, CYP2D6 poor metabolizers had drug exposures that were approximately 50% higher than for extensive metabolizers. About 7% of the population has this genetic mutation; however, because the drug is individually titrated to tolerability, no specific dosage adjustment is necessary for this population.
Since galantamine in metabolized by CYP2D6 and CYP3A4, inhibiting either of these isoenzymes will increase the cholinergic effects of galantamine.
Main article: Galantamine total synthesis
Galantamine is produced from natural resources and a patented total synthesis process. Many other synthetic methods exist but have not been implemented on an industrial scale.
The toxicity of organophosphates results primarily from their action as irreversible inhibitors of acetylcholinesterase.
Research supported in part by the US Army has led to a US patent application for the use of galantamine and/or its derivatives for treatment of organophosphate poisoning.
Galantamine given in addition to risperidone to autistic children has been shown to improve some of the symptoms of autism such as irritability, lethargy, and social withdrawal.
Galantamine may have some limited use in reducing the side-effects of anesthetics ketamine and diazepam. In one study, a control group of patients were given ketamine and diazepam and underwent anesthesia and surgery.
Though not approved by the FDA, there is interest in the recreational use of galantamine for its purported ability to induce lucid dreaming. One study has provided some limited evidence for this practice, although it is notable that its authors have financial ties to the Lucidity Institute.
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