Galantamine
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Galantamine
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| Systematic (IUPAC) name | |
| (4aS,6R,8aS)-5,6,9,10,11,12- hexahydro-3-methoxy-11- methyl-4aH-[1]benzofuro[3a,3,2-ef] [2]benzazepin-6-ol | |
| Identifiers | |
| CAS number | |
| ATC code | N06 |
| PubChem | |
| DrugBank | |
| Chemical data | |
| Formula | C17H21NO3 |
| Mol. mass | 287.354 g/mol |
| Pharmacokinetic data | |
| Bioavailability | 80 to 100% |
| Protein binding | 18% |
| Metabolism | Hepatic partially CYP450:CYP2D6/3A4 substrate |
| Half life | 7 hours |
| Excretion | Renal (95%, of which 32% unchanged), fecal (5%) |
| Therapeutic considerations | |
| Pregnancy cat. |
B |
| Legal status |
Rx and OTC |
| Routes | Oral |
Galantamine (trade names Razadyne, Razadyne ER, Reminyl, Nivalin) is a drug developed by Janssen Pharmaceutica, and used for the treatment of mild to moderate Alzheimer’s disease. It is an alkaloid that is obtained synthetically from the bulbs and flowers of the Caucasian snowdrop (Voronov’snowdrop), Lycoris radiata (Red Spider Lily), Galanthus woronowii (Amaryllidaceae) and related species. The active ingredient was discovered accidentally by a Bulgarian pharmacologist in the 1950s.[1]
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[edit] Pharmacology
Galantamine in its pure form is a white powder. Galantamine is a competitive and reversible cholinesterase inhibitor. It is believed it works by enhancing cholinergic function by increasing the concentration of acetylcholine in the brain. The atomics resolution 3D structure of the complex of galantamine and its target, acetylcholinesterase, was recentely determined by X-ray crystallography.[2] There is no evidence that galantamine alters the course of the underlying dementing process.[3] Galantamine has also shown activity in modulating the nicotinic cholinergic receptors to increase acetylcholine release.[4]
[edit] Pharmacokinetics
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 half-life of 7 hours. Peak effect of inhibiting acetylcholinesterase was achieved about one hour after a single oral dose of 8 mg in some healthy volunteers.
Plasma protein binding of galantamine is about 18%, which is relatively low.
[edit] Metabolism
The major route of metabolism for galantamine is through the liver, this accounts for approximately 75% of the total metabolism of galantamine. Hepatic cytochrome P450 (CYP) isoenzymes are the active enzymes for this metabolic route. In vitro studies have shown that CYP2D6 and CYP3A4 are involved in galantamine metabolism.
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.
[edit] Clinical use
[edit] Indications
Galantamine is indicated for mild to moderate Vascular Dementia and Alzheimer’s.[5][6]
The U.S. Food and Drug Administration (FDA) sent out a warning indicating that the product should not be used in patients of mild cognitive impairment (MCI) because of increased mortality observed in trials for MCI with galantamine.[7]
[edit] Available forms
The product is supplied in twice-a-day tablets, once-a-day extended release capsules, and in oral solution. The tablets come in 4mg, 8mg and 12mg forms. The capsules come in 8mg, 16mg, and 24mg forms.
[edit] Adverse events
In clinical trials, galantamine’s side effect profile was very similar to that of other cholinesterase inhibitors, with gastrointestinal symptoms being the most notable and most commonly observed. In practice, some other cholinesterase inhibitors might be better tolerated; however, a careful and gradual titration over more than three months may lead to equivalent long-term tolerability.[8]
[edit] Other use
[edit] Supplement for lucid dream and out-of-body experience
Some people who practice lucid dream (LD) or out-of-body experience (OBE) use galantamine to increase their odds to achieve LD or OBE. [9] [10] [11] By taking small amount of galantamine (around 4 to 8 mg) after 5 to 6 hours of deep sleep and practice an induction technique such as meditation, MILD or WILD [3] many people report more success with galantamine. [12]
There are also reports that taking galantamine without proper induction technique will not lead to LD or OBE but will result in only a vivid dream instead. It should also be noted that due to a long half life Galantamine will stay in the body for a period of up to and over 48 hours, as such it is advisable to space out the use of Galantamine over a period of three days so that the body does not build a resistance to the drug ruining its effectiveness. [9]
Galantamine used with choline bitartrate or Alpha-GPC can dramatically increase your odds of becoming lucid. [13] Some people report mixing galantamine with other nootropic can enhance the degree of lucidity, but this is still controversial since some mixtures may work for some people, but lead to failure for others.
[edit] Nootropic
Along with other cholinergics or acetylcholinesterase inhibitors such as Huperzine A, galantamine also has been used as nootropic or "brain enhancer". [14]
[edit] Caution
The FDA and other international health authorities have published an alert on galantamine based data from use on two studies during the treatment of mild cognitive impairment; higher mortality rates were seen in drug-treated patients.[15]
[edit] 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.
[edit] References
- ^ Scott LJ, Goa KL. Adis Review: Galantamine: a review of its use in Alzheimer's disease. Drugs 2000;60(5):1095-122 PMID 11129124
- ^ Greenblatt, HM, Kryger, G, Lewis, T, Silman, I, Sussman, JL "Structure of acetylcholinesterase complexed with (-)-galanthamine at 2.3Å resolution" FEBS Lett 1991; 463, 321-26. PMID 10606746
- ^ Ortho-McNeil Neurologics, “Razadyne ER US Product Insert”, May 2006. [1]
- ^ Woodruff-Pak DS, Vogel RW 3rd, Wenk GL, “Galantamine: effect on nicotinic receptor binding, acetylcholinesterase inhibition, and learning” Proc Natl Acad Sci U S A. 2001 Feb 13;98(4):2089-94. PMID 11172080
- ^ Galantamine Benefits Both Alzheimer’s Disease and Vascular Dementia
- ^ Galantamine Improves Attention in Alzheimer's
- ^ Alert for Healthcare Professionals on Galantamine
- ^ Birks J. “Cholinesterase inhibitors for Alzheimer's disease.” Cochrane Database Syst Rev. 2006 Jan 25;(1):CD005593. PMID 16437532
- ^ a b Thomas Yuschak (2006). Advanced Lucid Dreaming, 1st ed., Lulu Enterprises. ISBN 978-1-4303-0542-2.
- ^ Thomas Yuschak (2007). Pharmacological Induction of Lucid dreams.
- ^ Substances that enhance recall and lucidity during dreaming. Stephen LaBerge - US Patent. Retrieved on 2007-10-29.
- ^ Galantamine LDS Profile. Yuschak LDS Profiles. Retrieved on 2007-10-29.
- ^ What is the Role of Choline in Lucid dreaming? Thomas Yuschak.
- ^ Galantamine Protects Neurons and Memory Following Brain Injury
- ^ FDA alert (3/2005) on galantamine [2]
[edit] External links
- Razadyne (manufacturer's website)
- Galantamine (patient information)
- Galantamind (herbal Galantamine product)
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