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Galantamine | |
| 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. IUPAC Nomenclature is a system of naming Chemical compounds and of describing the science of Chemistry in general CAS registry numbers are unique numerical identifiers for Chemical compounds Polymers biological sequences mixtures and Alloys They are also referred to The Anatomical Therapeutic Chemical Classification System is used for the classification of drugs It is controlled by the WHO Collaborating Centre for Drug A section of the Anatomical Therapeutic Chemical Classification System containing Psychoanaleptics. PubChem is a Database of chemical Molecules The system is maintained by the National Center for Biotechnology Information (NCBI a component The DrugBank database available at the University of Alberta is a unique Bioinformatics and Cheminformatics resource that combines detailed drug (i A chemical formula is a way of expressing information about the Atoms that constitute a particular Chemical compound, and how the relationship between those atoms changes Carbon (kɑɹbən is a Chemical element with the symbol C and its Atomic number is 6 Hydrogen (ˈhaɪdrədʒən is the Chemical element with Atomic number 1 Nitrogen (ˈnaɪtɹəʤɪn is a Chemical element that has the symbol N and Atomic number 7 and Atomic weight 14 Oxygen (from the Greek roots ὀξύς (oxys (acid literally "sharp" from the taste of acids and -γενής (-genēs (producer literally begetteris the The molecular mass (abbreviated m of a substance, more commonly referred to as molecular weight and abbreviated as MW, is the Mass of one 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. In Pharmacology, bioavailability is used to describe the fraction of an administered Dose of unchanged drug that reaches the Systemic circulation, one of A drug's efficiency may be affected by the degree to which it binds to the proteins within Blood plasma. Drug metabolism is the Metabolism of drugs, their Biochemical modification or degradation usually through specialized enzymatic systems The liver is a vital organ in the human body and is present in Vertebrates and some other animals Cytochrome P450 (abbreviated CYP, P450, infrequently CYP450) is a very large and diverse superfamily of Hemoproteins found in all Domains Cytochrome P450 2D6 (CYP2D6 a member of the Cytochrome P450 mixed-function oxidase system is one of the most important enzymes involved in the metabolism of Xenobiotics Cytochrome P450 3A4 (abbreviated CYP3A4) ( a member of the Cytochrome P450 mixed-function oxidase system is one of the most important enzymes involved in the metabolism The biological half-life of a substance is the time it takes for a substance (drug radioactive nuclide or other to lose half of its pharmacologic physiologic or radiologic activity Excretion is the process of eliminating waste products of Metabolism and other non-useful materials The kidneys are complicated organs that have numerous biological roles The pregnancy category of a pharmaceutical agent is an assessment of the risk of fetal injury due to the pharmaceutical if it is used as directed by the mother during The regulation of therapeutic goods, that is drugs and therapeutic devices, varies by jurisdiction In Pharmacology and Toxicology, a route Janssen Pharmaceutica, is a Pharmaceutical company based in Beerse, in the Campine region of the province of Antwerp, Belgium. Alzheimer's disease ( AD) also called Alzheimer disease or simply Alzheimer's, is the most common form of Dementia. 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. This article is about the chemical compounds alkaloids For the Pharmaceutical company in the Republic of Macedonia see Alkaloid (company. The common snowdrop ( Galanthus nivalis) is the best-known representative of a small Genus of about 20 species in the family Amaryllidaceae that The active ingredient was discovered accidentally by a Bulgarian pharmacologist in the 1950s. [1]
Contents |
Pharmacology
Galantamine in its pure form is a white powder. Galantamine is a competitive and reversible cholinesterase inhibitor. Competitive inhibition is a form of enzyme inhibition where binding of the inhibitor to the Enzyme prevents binding of the substrate and vice versa Enzyme inhibitors are Molecules that bind to Enzymes and decrease their activity. An acetylcholinesterase inhibitor or anti-cholinesterase is a chemical that inhibits the Cholinesterase enzyme from breaking down Acetylcholine It is believed it works by enhancing cholinergic function by increasing the concentration of acetylcholine in the brain. The Chemical compound acetylcholine (often abbreviated ACh) is a Neurotransmitter in both the Peripheral nervous system (PNS and Central 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. Structure Nicotinic receptors with a molecular mass of 290 kDa, are made up of five subunits arranged symmetrically around the central pore. [4]
Pharmacokinetics
Absorption of galantamine is rapid and complete and shows linear pharmacokinetics. It is well absorbed with absolute oral bioavailability between 80 and 100%. In Pharmacology, bioavailability is used to describe the fraction of an administered Dose of unchanged drug that reaches the Systemic circulation, one of It has a half-life of 7 hours. The biological half-life of a substance is the time it takes for a substance (drug radioactive nuclide or other to lose half of its pharmacologic physiologic or radiologic activity 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. A drug's efficiency may be affected by the degree to which it binds to the proteins within Blood plasma.
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. Cytochrome P450 (abbreviated CYP, P450, infrequently CYP450) is a very large and diverse superfamily of Hemoproteins found in all Domains Isozymes (also known as isoenzymes) are Enzymes that differ in amino acid sequence but catalyze the same chemical reaction In vitro studies have shown that CYP2D6 and CYP3A4 are involved in galantamine metabolism. Cytochrome P450 2D6 (CYP2D6 a member of the Cytochrome P450 mixed-function oxidase system is one of the most important enzymes involved in the metabolism of Xenobiotics Cytochrome P450 3A4 (abbreviated CYP3A4) ( a member of the Cytochrome P450 mixed-function oxidase system is one of the most important enzymes involved in the metabolism
For Razadyne ER (the once-a-day formulation), CYP2D6 poor metabolizers had drug exposures that were approximately 50% higher than for extensive metabolizers. Drug metabolism is the Metabolism of drugs, their Biochemical modification or degradation usually through specialized enzymatic systems 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.
Clinical use
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]
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.
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. An adverse drug reaction (abbreviated ADR) or adverse drug event (abbreviated ADE) is an expression that describes the unwanted negative consequences 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]
Other use
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. An out-of-body experience ( OBE or sometimes OOBE) is an experience that typically involves a sensation of floating outside of one's body and in some cases perceiving [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. Meditation is a mental discipline by which one attempts to get beyond the conditioned "thinking" mind into a deeper state of relaxation or awareness [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. Choline is an Organic compound, classified as a water-soluble Essential nutrient and usually grouped within the Vitamin B complex L-Alpha Glycerylphosphorylcholine ( Alpha GPC, Choline alfoscerate) is a naturally occurring Phospholipid precursor and metabolite [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. '''Nootropics''' popularly referred to as " smart drugs " " smart nutrients " " cognitive enhancers " and " brain enhancers
Nootropic
Along with other cholinergics or acetylcholinesterase inhibitors such as Huperzine A, galantamine also has been used as nootropic or "brain enhancer". Huperzine A, is a naturally occurring sesquiterpene Alkaloid found in the plant extracts of the Firmoss Huperzia serrata. '''Nootropics''' popularly referred to as " smart drugs " " smart nutrients " " cognitive enhancers " and " brain enhancers [14]
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]
Total synthesis
Galantamine is produced from natural resources and a patented total synthesis process. Galanthamine total synthesis concerns the Total synthesis of Galanthamine, a Drug used for the treatment of mild to moderate Alzheimer’s disease In principle a total synthesis is the complete Chemical synthesis of complex organic Molecules from simpler pieces usually without the aid of biological Many other synthetic methods exist but have not been implemented on an industrial scale.
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. Year 2007 ( MMVII) was a Common year starting on Monday of the Gregorian calendar in the 21st century. Events 437 - Valentinian III, Western Roman Emperor, marries Licinia Eudoxia, daughter of his cousin Theodosius II
- ^ Galantamine LDS Profile. Yuschak LDS Profiles. Retrieved on 2007-10-29. Year 2007 ( MMVII) was a Common year starting on Monday of the Gregorian calendar in the 21st century. Events 437 - Valentinian III, Western Roman Emperor, marries Licinia Eudoxia, daughter of his cousin Theodosius II
- ^ 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]
External links
- Razadyne (manufacturer's website)
- Galantamine (patient information)
- Galantamind (herbal Galantamine product)
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