Galantamine

Last updated

Galantamine
Galantamine.svg
Galantamine 3D.png
Clinical data
Trade names Razadyne, others
AHFS/Drugs.com Monograph
MedlinePlus a699058
License data
Pregnancy
category
Routes of
administration 		By mouth
ATC code
Legal status
Legal status
Pharmacokinetic data
Bioavailability 80–100%
Protein binding 18%
Metabolism Liver partially CYP450:CYP2D6/3A4 substrate
Elimination half-life 7 hours
Excretion Kidney (95%, of which 32% unchanged), fecal (5%)
Identifiers
  • (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
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
PDB ligand
CompTox Dashboard (EPA)
ECHA InfoCard 100.118.289 OOjs UI icon edit-ltr-progressive.svg
Chemical and physical data
Formula C17H21NO3
Molar mass 287.359 g·mol−1
3D model (JSmol)
Melting point 126.5 °C (259.7 °F)
  • O(c2c1O[C@H]4C[C@@H](O)/C=C\[C@@]43c1c(cc2)CN(C)CC3)C
  • InChI=1S/C17H21NO3/c1-18-8-7-17-6-5-12(19)9-14(17)21-16-13(20-2)4-3-11(10-18)15(16)17/h3-6,12,14,19H,7-10H2,1-2H3/t12-,14-,17-/m0/s1 Yes check.svgY
  • Key:ASUTZQLVASHGKV-JDFRZJQESA-N Yes check.svgY
   (verify)

Galantamine is a type of acetylcholinesterase inhibitor. It is an alkaloid extracted from the bulbs and flowers of Galanthus nivalis (common snowdrop), Galanthus caucasicus (Caucasian snowdrop), Galanthus woronowii (Voronov's snowdrop), and other members of the family Amaryllidaceae , such as Narcissus (daffodil), Leucojum aestivum (snowflake), and Lycoris including Lycoris radiata (red spider lily). [5] It can also be produced synthetically.

Contents

Galantamine is primarily known for its potential to slow cognitive decline. It is used clinically for treating early-stage Alzheimer's disease and memory impairments, although it has had limited success with the more advanced condition of dementia. [6] [7] [8] [9]

It works by increasing the amount of a type of neurotransmitter named acetylcholine by the inhibiting activity of an enzyme called acetylcholinesterase known for breaking down acetylcholine. This elevates and prolongs acetylcholine levels boosting acetylcholine's neuromodulatory functionality, subsequently enhancing functionality of the various cognitions that acetylcholine is involved in, such as memory processing, reasoning, and thinking. [6] Galantamine may cause serious adverse effects, such as stomach bleeding, liver injury or chest pain. [6] [8]

Galantamine was isolated for the first time from bulbs of Galanthus nivalis (common snowdrop) in the Soviet Union in the 1940s. [10] The active ingredient was extracted, identified, and studied, in particular in relation to acetylcholinesterase (AChE)-inhibiting properties. [11] [12] The first industrial process was developed in 1959. [13] [14] However, it was not until the 1990s when full-scale synthesis was upscaled and optimized. [15]

Medical uses

Galantamine, sold under the brand name Razadyne among others, is indicated for the treatment of mild to moderate vascular dementia and Alzheimer's disease. [6] [7] The first person to extract galantamine and theorize its usefulness in medicine, was the Bulgarian chemist Dimitar Paskov in 1959. In the United States, it is approved by the Food and Drug Administration (FDA) for the treatment of mild to moderate dementia. [8] [16] Galantamine may not be effective for treating mild cognitive impairment. [17]

Alzheimer's disease

Alzheimer's disease is characterized by the impairment of cholinergic function. [6] [8] One hypothesis is that this impairment contributes to the cognitive deficits caused by the disease. This hypothesis forms the basis for use of galantamine as a cholinergic enhancer in the treatment of Alzheimer's. [6] [8] Galantamine inhibits acetylcholinesterase, an enzyme which hydrolyzes acetylcholine. [6] [8] As a result of acetylcholinesterase inhibition, galantamine increases the availability of acetylcholine for synaptic transmission. [8] Additionally, galantamine binds to the allosteric sites of nicotinic receptors, which causes a conformational change. [18] This allosteric modulation increases the nicotinic receptor's response to acetylcholine. [8] The activation of presynaptic nicotinic receptors increases the release of acetylcholine, further increasing the availability of acetylcholine. [8] Galantamine's competitive inhibition of acetylcholinesterase and allosteric nicotinic modulation serves as a dual mechanism of action. [18]

To reduce the prevalence of negative side effects associated with galantamine, such as nausea and vomiting, a dose-escalation scheme may be used. [19] The use of a dose-escalation scheme has been well accepted in countries where galantamine is used. [19] A dose-escalation scheme for Alzheimer's treatment involves a recommended starting dosage of 4 mg galantamine tablets given twice a day (8 mg/day). [6] After a minimum of 4 weeks, the dosage may then be increased to 8 mg given twice a day (16 mg/day). [6] After a minimum of 4 weeks at 16 mg/day, the treatment may be increased to 12 mg given twice a day (24 mg/day). [6] Dosage increases are based upon the assessment of clinical benefit as well as tolerability of the previous dosage. [6] If treatment is interrupted for more than three days, the process is usually restarted, beginning at the starting dosage, and re-escalating to the current dose. [6] It has been found that a dosage between 16–24 mg/day is the optimal dosage. [20]

In December 2023, the FDA approved a New Drug Application (NDA) for a pro-drug of galantamine called ALPHA-1062. [21] In July 2024, The FDA approved benzgalantamine (Zunveyl), previously known as ALPHA-1062, to treat mild-to-moderate Alzheimer's disease. [22]

Side effects

The adverse effect profile of galantamine includes potential for allergic reaction, including hives, swelling of the face or throat, and skin rash. [6] [23] Using galantamine may cause chest pain, bloody urine, stomach bleeding, and liver injury, among other side effects. [6] [23] Nausea, vomiting, diarrhea, dizziness, and headache are considered common side effects. [6]

A gradual titration over more than three months may enable long-term tolerability in some people. [24]

Galantamine has a wide spectrum of interactions with other medications and medical disorders, requiring close assessment between the physician and patient. [23]

Pharmacology

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. [6]

Galantamine is a potent allosteric potentiating ligand of human nicotinic acetylcholine receptors (nAChRs) α4β2, α3β4, and α6β4, and chicken/mouse nAChRs α7/5-HT3 in certain areas of the brain. [6] [25] By binding to the allosteric site of the nAChRs, a conformational change occurs which increases the receptors response to acetylcholine. [8] This modulation of the nicotinic cholinergic receptors on cholinergic neurons in turn causes an increase in the amount of acetylcholine released. [26] However, recent studies suggest that Galantamine does not functionally act at human nAChRs α4β2 or α7 as a positive allosteric modulator. [27] [28]

Galantamine also works as a weak competitive and reversible cholinesterase inhibitor in all areas of the body. [6] 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 Synapse FINISHED.png
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). [29] There is no evidence that galantamine alters the course of the underlying dementing process. [30]

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 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. [18]

Plasma protein binding of galantamine is about 18%, which is relatively low.

Metabolism

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. [18]

In humans, several metabolic pathways for galantamine exist. [25] These pathways lead to the formation of a number of different metabolites. [25] One of the metabolites that may result can be formed through the glucuronidation of galantamine. [25] Additionally, galantamine may undergo oxidation or demethylation at its nitrogen atom, forming two other possible metabolites. [25] Galantamine can undergo demethylation at its oxygen atom, forming an intermediate which can then undergo glucuronidation or sulfate conjugation. [25] Lastly, galantamine may be oxidized and then reduced before finally undergoing demethylation or oxidation at its nitrogen atom, or demethylation and subsequent glucuronidation at its oxygen atom. [25]

Metabolic pathways of galantamine Galantamine Metabolism.png
Metabolic pathways of galantamine

Drug interactions

Since galantamine is metabolized by CYP2D6 and CYP3A4, inhibiting either of these isoenzymes will increase the cholinergic effects of galantamine. [18] Inhibiting these enzymes may lead to adverse effects. [18] It was found that paroxetine, an inhibitor of CYP2D6, increased the bioavailability of galantamine by 40%. [18] The CYP3A4 inhibitors ketoconazole and erythromycin increased the bioavailability of galantamine by 30% and 12%, respectively. [18]

Extraction and synthesis

Since the alkaloid is isolated from botanical sources containing low amounts (0.1%) by weight, extraction yields are low. [31] Although galantamine can be produced from natural resources, it also has many industrial syntheses, such as by Janssen, Ortho-McNeil Pharmaceutical, Shire, and Takeda Pharmaceutical Company. [32]

Research

Organophosphate poisoning

The toxicity of organophosphates results primarily from their action as irreversible inhibitors of acetylcholinesterase. [33] Inhibiting acetylcholinesterase causes an increase in acetylcholine, as the enzyme is no longer available to catalyze its breakdown. [33] In the peripheral nervous system, acetylcholine accumulation can cause an overstimulation of muscarinic receptors followed by a desensitization of nicotinic receptors. [33] This leads to severe skeletal muscle fasciculations (involuntary contractions). [33] The effects on the central nervous system include anxiety, restlessness, confusion, ataxia, tremors, seizures, cardiorespiratory paralysis, and coma. [33] As a reversible acetylcholinesterase inhibitor, galantamine has the potential to serve as an effective organophosphate poisoning treatment by preventing irreversible acetylcholinesterase inhibition. [33] Additionally, galantamine has anticonvulsant properties which may make it even more desirable as an antidote. [33]

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. [33] The indications for use of galantamine in the patent application include poisoning by nerve agents "including but not limited to soman, sarin, and VX, tabun, and Novichok agents". Galantamine was studied in the research cited in the patent application for use along with the well-recognized nerve agent antidote atropine. According to the investigators, an unexpected synergistic interaction occurred between galantamine and atropine in an amount of 6 mg/kg or higher. Increasing the dose of galantamine from 5 to 8 mg/kg decreased the dose of atropine needed to protect experimental animals from the toxicity of soman in dosages 1.5 times the dose generally required to kill half the experimental animals. [34]

Autism

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. [35] Additionally, the cholinergic and nicotinic receptors are believed to play a role in attentional processes. [36] Some studies have noted that cholinergic and nicotinic treatments have improved attention in autistic children. [36] As such, it is hypothesized that galantamine's dual action mechanism might have a similar effect in treating autistic children and adolescents. [36]

Anesthesia

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. [37] The experimental group was given ketamine, diazepam, and nivalin (of which the active ingredient is galantamine). [37] The degree of drowsiness and disorientation of the two groups was then assessed 5, 10, 15, 30 and 60 minutes after surgery. [37] The group that had taken nivalin were found to be more alert 5, 10, and 15 minutes after the surgery. [37]

Oneirogen

Galantamine is known to have oneirogenic properties. Research has demonstrated its potential to increase dream recall, dream self-awareness and dream vividness. The enhancement of such dream properties can facilitate the induction of lucid dreams. [38] [39]

Related Research Articles

<span class="mw-page-title-main">Acetylcholine</span> Organic chemical and neurotransmitter

Acetylcholine (ACh) is an organic compound that functions in the brain and body of many types of animals as a neurotransmitter. Its name is derived from its chemical structure: it is an ester of acetic acid and choline. Parts in the body that use or are affected by acetylcholine are referred to as cholinergic.

<span class="mw-page-title-main">Cholinergic</span> Agent which mimics choline

Cholinergic agents are compounds which mimic the action of acetylcholine and/or butyrylcholine. In general, the word "choline" describes the various quaternary ammonium salts containing the N,N,N-trimethylethanolammonium cation. Found in most animal tissues, choline is a primary component of the neurotransmitter acetylcholine and functions with inositol as a basic constituent of lecithin. Choline also prevents fat deposits in the liver and facilitates the movement of fats into cells.

<span class="mw-page-title-main">Edrophonium</span>

Edrophonium is a readily reversible acetylcholinesterase inhibitor. It prevents breakdown of the neurotransmitter acetylcholine and acts by competitively inhibiting the enzyme acetylcholinesterase, mainly at the neuromuscular junction. It is sold under the trade names Tensilon and Enlon.

<span class="mw-page-title-main">Neuromuscular junction</span> Junction between the axon of a motor neuron and a muscle fiber

A neuromuscular junction is a chemical synapse between a motor neuron and a muscle fiber.

<span class="mw-page-title-main">Donepezil</span> Medication used for dementia

Donepezil, sold under the brand name Aricept among others, is a medication used to treat dementia of the Alzheimer's type. It appears to result in a small benefit in mental function and ability to function. Use, however, has not been shown to change the progression of the disease. Treatment should be stopped if no benefit is seen. It is taken by mouth or via a transdermal patch.

<span class="mw-page-title-main">Physostigmine</span> Chemical compound

Physostigmine is a highly toxic parasympathomimetic alkaloid, specifically, a reversible cholinesterase inhibitor. It occurs naturally in the Calabar bean and the fruit of the Manchineel tree.

<span class="mw-page-title-main">Memantine</span> Medication used to treat Alzheimers disease

Memantine, sold under the brand name Axura among others, is a medication used to slow the progression of moderate-to-severe Alzheimer's disease. It is taken by mouth.

<span class="mw-page-title-main">Huperzine A</span> Chemical compound

Huperzine A is a naturally-occurring sesquiterpene alkaloid compound found in the firmoss Huperzia serrata and in varying quantities in other food Huperzia species, including H. elmeri, H. carinat, and H. aqualupian. Huperzine A has been investigated as a treatment for neurological conditions such as Alzheimer's disease, but a 2013 meta-analysis of those studies concluded that they were of poor methodological quality and the findings should be interpreted with caution. Huperzine A inhibits the breakdown of the neurotransmitter acetylcholine (ACh) by the enzyme acetylcholinesterase. It is also an antagonist of the NMDA-receptor. It is commonly available over the counter as a nutritional supplement and marketed as a memory and concentration enhancer.

A cholinergic crisis is an over-stimulation at a neuromuscular junction due to an excess of acetylcholine (ACh), as a result of the inactivity of the AChE enzyme, which normally breaks down acetylcholine.

A nicotinic agonist is a drug that mimics the action of acetylcholine (ACh) at nicotinic acetylcholine receptors (nAChRs). The nAChR is named for its affinity for nicotine.

<span class="mw-page-title-main">Acetylcholinesterase</span> Primary cholinesterase in the body

Acetylcholinesterase (HGNC symbol ACHE; EC 3.1.1.7; systematic name acetylcholine acetylhydrolase), also known as AChE, AChase or acetylhydrolase, is the primary cholinesterase in the body. It is an enzyme that catalyzes the breakdown of acetylcholine and some other choline esters that function as neurotransmitters:

<span class="mw-page-title-main">Alpha-7 nicotinic receptor</span> Type of cell receptor found in humans

The alpha-7 nicotinic receptor, also known as the α7 receptor, is a type of nicotinic acetylcholine receptor implicated in long-term memory, consisting entirely of α7 subunits. As with other nicotinic acetylcholine receptors, functional α7 receptors are pentameric [i.e., (α7)5 stoichiometry].

<span class="mw-page-title-main">GTS-21</span> Chemical compound

GTS-21 is a drug that has been shown to enhance memory and cognitive function. It has been studied for its potential therapeutic uses, particularly in the treatment of neurodegenerative diseases and psychiatric disorders.

<span class="mw-page-title-main">Acetylcholinesterase inhibitor</span> Drugs that inhibit acetylcholinesterase

Acetylcholinesterase inhibitors (AChEIs) also often called cholinesterase inhibitors, inhibit the enzyme acetylcholinesterase from breaking down the neurotransmitter acetylcholine into choline and acetate, thereby increasing both the level and duration of action of acetylcholine in the central nervous system, autonomic ganglia and neuromuscular junctions, which are rich in acetylcholine receptors. Acetylcholinesterase inhibitors are one of two types of cholinesterase inhibitors; the other being butyryl-cholinesterase inhibitors. Acetylcholinesterase is the primary member of the cholinesterase enzyme family.

<span class="mw-page-title-main">Cholinesterase inhibitor</span> Chemicals which prevent breakdown of acetylcholine and butyrylcholine

Cholinesterase inhibitors (ChEIs), also known as anti-cholinesterase, are chemicals that prevent the breakdown of the neurotransmitter acetylcholine or butyrylcholine. This increases the amount of the acetylcholine or butyrylcholine in the synaptic cleft that can bind to muscarinic receptors, nicotinic receptors and others. This group of inhibitors is divided into two subgroups, acetylcholinesterase inhibitors (AChEIs) and butyrylcholinesterase inhibitors (BChEIs).

<span class="mw-page-title-main">Rivastigmine</span> Chemical compound

Rivastigmine is a cholinesterase inhibitor used for the treatment of mild to moderate Alzheimer's disease. The drug can be administered orally or via a transdermal patch; the latter form reduces the prevalence of side effects, which typically include nausea and vomiting.

<span class="mw-page-title-main">Phenserine</span> Chemical compound

Phenserine is a synthetic drug which has been investigated as a medication to treat Alzheimer's disease (AD), as the drug exhibits neuroprotective and neurotrophic effects.

<span class="mw-page-title-main">Huprine X</span> Chemical compound

Huprine X is a synthetic cholinergic compound developed as a hybrid between the natural product Huperzine A and the synthetic drug tacrine. It is one of the most potent reversible inhibitors of acetylcholinesterase known, with a binding affinity of 0.026nM, as well as showing direct agonist activity at both nicotinic and muscarinic acetylcholine receptors. In animal studies it has nootropic and neuroprotective effects, and is used in research into Alzheimer's disease, and although huprine X itself has not been researched for medical use in humans, a large family of related derivatives have been developed.

The neuronal acetylcholine receptor subunit alpha-5, or alpha-5 nicotinic acetylcholine receptor(α5 nAChR) also known as the α5 receptor is a type of ligand gated neuronal type subunit of the nicotinic acetylcholine receptor involved in pain regulation encoded in the human by the CHRNA5 gene. This receptor is commonly associated with nicotine addiction, immunotherapy, cancer, pain and attention.

<span class="mw-page-title-main">Neuromuscular drug</span>

Neuromuscular drugs are chemical agents that are used to alter the transmission of nerve impulses to muscles, causing effects such as temporary paralysis of targeted skeletal muscles. Most neuromuscular drugs are available as quaternary ammonium compounds which are derived from acetylcholine (ACh). This allows neuromuscular drugs to act on multiple sites at neuromuscular junctions, mainly as antagonists or agonists of post-junctional nicotinic receptors. Neuromuscular drugs are classified into four main groups, depolarizing neuromuscular blockers, non-depolarizing neuromuscular blockers, acetylcholinesterase inhibitors, and butyrylcholinesterase inhibitors.

References

  1. ↑ "Galantamine Use During Pregnancy". Drugs.com. February 18, 2019. Archived from the original on February 25, 2020. Retrieved February 24, 2020.
  2. ↑ Anvisa (March 31, 2023). "RDC Nº 784 - Listas de Substâncias Entorpecentes, Psicotrópicas, Precursoras e Outras sob Controle Especial" [Collegiate Board Resolution No. 784 - Lists of Narcotic, Psychotropic, Precursor, and Other Substances under Special Control] (in Brazilian Portuguese). Diário Oficial da União (published April 4, 2023). Archived from the original on August 3, 2023. Retrieved August 16, 2023.
  3. ↑ "Razadyne- galantamine hydrobromide tablet, film coated". DailyMed. November 11, 2010. Archived from the original on April 26, 2023. Retrieved August 5, 2024.
  4. ↑ "Active substance: galantamine" (PDF). List of nationally authorised medicinal products, Human Medicines Evaluation Division. European Medicines Agency. November 12, 2020. Archived (PDF) from the original on October 31, 2021. Retrieved December 19, 2020.
  5. ↑ Theodorou M. "Sustainable Production of the Natural Product Galanthamine (Defra), NF0612". NNFCC Project Factsheet. The National Non-Food Crops Centre (NNFCC). Archived from the original on March 14, 2012.
  6. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 "Galantamine". Drugs.com. August 8, 2023. Archived from the original on October 14, 2018. Retrieved March 26, 2024.
  7. 1 2 Birks J (January 2006). Birks JS (ed.). "Cholinesterase inhibitors for Alzheimer's disease". The Cochrane Database of Systematic Reviews. 2016 (1): CD005593. doi:10.1002/14651858.CD005593. PMC   9006343 . PMID   16437532.
  8. 1 2 3 4 5 6 7 8 9 10 Kalola UK, Nguyen H (March 12, 2023). "Galantamine". StatPearls Publishing, US National Library of Medicine. Archived from the original on December 26, 2023. Retrieved March 26, 2024.
  9. ↑ Battle CE, Abdul-Rahim AH, Shenkin SD, Hewitt J, Quinn TJ (February 2021). "Cholinesterase inhibitors for vascular dementia and other vascular cognitive impairments: a network meta-analysis". The Cochrane Database of Systematic Reviews. 2021 (2): CD013306. doi:10.1002/14651858.CD013306.pub2. PMC   8407366 . PMID   33704781.
  10. ↑ Proskurnina NF, Areshknina LY. J. Chim. Gen. USSR. Chem. Abst. 1947;1948;1742(1595h):1216. No title available.
  11. ↑ Heinrich M (2004). "Snowdrops: The heralds of spring and a modern drug for Alzheimer's disease". Pharmaceutical Journal. 273 (7330): 905–6. OCLC   98892008. Archived from the original on October 23, 2018. Retrieved July 30, 2015.
  12. ↑ Mashkovsky MD, Kruglikova-Lvova RP (1951). "On the pharmacology of the new alkaloid galantamine". Farmakologia Toxicologia. 14: 27–30.
  13. ↑ Heinrich M, Lee Teoh H (June 2004). "Galanthamine from snowdrop--the development of a modern drug against Alzheimer's disease from local Caucasian knowledge". Journal of Ethnopharmacology. 92 (2–3): 147–162. doi:10.1016/j.jep.2004.02.012. PMID   15137996.
  14. ↑ Scott LJ, Goa KL (November 2000). "Galantamine: a review of its use in Alzheimer's disease". Drugs. 60 (5): 1095–1122. doi:10.2165/00003495-200060050-00008. PMID   11129124. S2CID   250305879.
  15. ↑ "Galantamine". alzforum. Archived from the original on November 17, 2019. Retrieved November 17, 2019.
  16. ↑ "Galantamine hydrobromide (trademark)" (PDF). US Food and Drug Administration. 2004. Archived (PDF) from the original on July 13, 2020. Retrieved December 17, 2017.
  17. ↑ Tricco AC, Soobiah C, Berliner S, Ho JM, Ng CH, Ashoor HM, et al. (November 2013). "Efficacy and safety of cognitive enhancers for patients with mild cognitive impairment: a systematic review and meta-analysis". CMAJ. 185 (16): 1393–401. doi:10.1503/cmaj.130451. PMC   3826344 . PMID   24043661.
  18. 1 2 3 4 5 6 7 8 Farlow MR (2003). "Clinical pharmacokinetics of galantamine". Clinical Pharmacokinetics. 42 (15): 1383–92. doi:10.2165/00003088-200342150-00005. PMID   14674789. S2CID   36855768.
  19. 1 2 Erkinjuntti T, Kurz A, Gauthier S, Bullock R, Lilienfeld S, Damaraju CV (April 2002). "Efficacy of galantamine in probable vascular dementia and Alzheimer's disease combined with cerebrovascular disease: a randomised trial". Lancet. 359 (9314): 1283–90. doi:10.1016/S0140-6736(02)08267-3. PMID   11965273. S2CID   1172847.
  20. ↑ Hager K, Baseman AS, Nye JS, Brashear HR, Han J, Sano M, et al. (2014). "Effects of galantamine in a 2-year, randomized, placebo-controlled study in Alzheimer's disease". Neuropsychiatric Disease and Treatment. 10: 391–401. doi: 10.2147/NDT.S57909 . PMC   3937252 . PMID   24591834.
  21. ↑ "Alpha Cognition Announces FDA Acceptance of New Drug Application for ALPHA-1062 for Mild-to-Moderate Alzheimer's Disease" (Press release). Alpha Cognition. December 7, 2023. Archived from the original on April 16, 2024. Retrieved August 5, 2024– via Business Wire.
  22. ↑ "Alpha Cognition's Oral Therapy Zunveyl Receives FDA Approval to Treat Alzheimer's Disease" (Press release). Alpha Cognition. July 29, 2024. Archived from the original on August 4, 2024. Retrieved August 4, 2024– via Business Wire.
  23. 1 2 3 "Galantamine". Mayo Clinic. 2024. Archived from the original on March 26, 2024. Retrieved March 26, 2024.
  24. ↑ Birks J (January 2006). Birks J (ed.). "Cholinesterase inhibitors for Alzheimer's disease". The Cochrane Database of Systematic Reviews. 2016 (1): CD005593. doi:10.1002/14651858.CD005593. PMC   9006343 . PMID   16437532.
  25. 1 2 3 4 5 6 7 Mannens GS, Snel CA, Hendrickx J, Verhaeghe T, Le Jeune L, Bode W, et al. (May 2002). "The metabolism and excretion of galantamine in rats, dogs, and humans". Drug Metabolism and Disposition. 30 (5): 553–63. doi:10.1124/dmd.30.5.553. PMID   11950787. S2CID   6795456.
  26. ↑ Woodruff-Pak DS, Vogel RW, Wenk GL (February 2001). "Galantamine: effect on nicotinic receptor binding, acetylcholinesterase inhibition, and learning". Proceedings of the National Academy of Sciences of the United States of America. 98 (4): 2089–94. Bibcode:2001PNAS...98.2089W. doi: 10.1073/pnas.031584398 . JSTOR   3055005. PMC   29386 . PMID   11172080.
  27. ↑ Moerke MJ, McMahon LR, Wilkerson JL (April 2020). "More than Smoke and Patches: The Quest for Pharmacotherapies to Treat Tobacco Use Disorder". Pharmacological Reviews. 72 (2): 527–557. doi:10.1124/pr.119.018028. PMC   7090325 . PMID   32205338. Archived from the original on October 8, 2021. Retrieved October 24, 2020.
  28. ↑ Kowal NM, Ahring PK, Liao WY, Indurti DC, Harvey BS, O'Connor SM, et al. (July 2018). "Galantamine is not a positive allosteric modulator of human α4β2 or α7 nicotinic acetylcholine receptors". British Journal of Pharmacology . 175 (14): 2911–2925. doi:10.1111/bph.14329. PMC   6016680 . PMID   29669164.
  29. ↑ Greenblatt HM, Kryger G, Lewis T, Silman I, Sussman JL (December 1999). "Structure of acetylcholinesterase complexed with (-)-galanthamine at 2.3 A resolution". FEBS Letters. 463 (3): 321–6. Bibcode:1999FEBSL.463..321G. doi: 10.1016/S0014-5793(99)01637-3 . PMID   10606746. S2CID   573270.
  30. ↑ "Ortho-McNeil Neurologics, "Razadyne ER US Product Insert", May 2006" (PDF). Archived from the original (PDF) on December 22, 2009. Retrieved December 21, 2009.
  31. ↑ Kim JK, Park SU (2017). "Pharmacological aspects of galantamine for the treatment of Alzheimer's disease". EXCLI Journal. 16: 35–39. doi:10.17179/excli2016-820. PMC   5318685 . PMID   28337117.
  32. ↑ Mucke HA (November 2015). "The case of galantamine: repurposing and late blooming of a cholinergic drug". Future Science OA. 1 (4): FSO73. doi:10.4155/fso.15.73. PMC   5137937 . PMID   28031923.
  33. 1 2 3 4 5 6 7 8 Albuquerque EX, Pereira EF, Aracava Y, Fawcett WP, Oliveira M, Randall WR, et al. (August 2006). "Effective countermeasure against poisoning by organophosphorus insecticides and nerve agents". Proceedings of the National Academy of Sciences of the United States of America. 103 (35): 13220–5. Bibcode:2006PNAS..10313220A. doi: 10.1073/pnas.0605370103 . PMC   1550772 . PMID   16914529.
  34. ↑ Albuquerque, Edson X, Adler, Michael, Pereira, Edna F.R. (January 22, 2009). "United States Patent Application 20090023706". US Patent and Trademark Office. Archived from the original on July 13, 2020. Retrieved May 27, 2016.
  35. ↑ Ghaleiha A, Ghyasvand M, Mohammadi MR, Farokhnia M, Yadegari N, Tabrizi M, et al. (July 2014). "Galantamine efficacy and tolerability as an augmentative therapy in autistic children: A randomized, double-blind, placebo-controlled trial". Journal of Psychopharmacology. 28 (7): 677–85. doi:10.1177/0269881113508830. PMID   24132248. S2CID   206491732.
  36. 1 2 3 Nicolson R, Craven-Thuss B, Smith J (October 2006). "A prospective, open-label trial of galantamine in autistic disorder". Journal of Child and Adolescent Psychopharmacology. 16 (5): 621–9. doi:10.1089/cap.2006.16.621. PMID   17069550.
  37. 1 2 3 4 Chakalova E, Marinova M, Srebreva M, Anastasov D, Ploskov K (1987). "[Attempt to eliminate residual somnolence and disorientation with nivaline after anesthesia with ketalar and diazepam for minor obstetrical and gynecologic surgery]". Akusherstvo I Ginekologiia (in Bulgarian). 26 (3): 28–31. PMID   3631427.
  38. ↑ Tan S, Fan J (June 2023). "A systematic review of new empirical data on lucid dream induction techniques". Journal of Sleep Research. 32 (3): e13786. doi:10.1111/jsr.13786. PMID   36408823.
  39. ↑ Sparrow G, Hurd R, Carlson R, Molina A (August 2018). "Exploring the effects of galantamine paired with meditation and dream reliving on recalled dreams: Toward an integrated protocol for lucid dream induction and nightmare resolution". Consciousness and Cognition. 63. Elsevier BV: 74–88. doi:10.1016/j.concog.2018.05.012. PMID   29960246.
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.