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Pathway Description
Donepezil Action Pathway
Homo sapiens
Drug Action Pathway
Created: 2023-08-03
Last Updated: 2023-11-27
Donepezil is an acetylcholinesterase inhibitor also known as Adlarity, Aricept and Namzaric, that is used in the treatment of Alzheimer's Disease and dementia. It is administered orally or transdermally, sometimes in combination with memantine in order to treat moderate to severe dementia. Donepezil selectively inhibits the acetylcholinesterase enzyme, by doing so it is believed to enhance cholinergic transmission to relieve the symptoms of Alzheimer's and dementia. Normally acetylcholinesterase breaks down acetylcholine, this inhibited its enhances cholinergic transmission. Donepezil goes through first-pass metabolism by CYP3A4 and CYP2D6 into metabolites which can be further broken down by dealkylation, hydroxylation, oxidation, hydrolysis and glucuronidation.
References
Donepezil Pathway References
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Pubmed: 12105320
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Pubmed: 12756141
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Pubmed: 1337937
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Pubmed: 11239002
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Pubmed: 2263619
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Pubmed: 8299725
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Pubmed: 1321501
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Pubmed: 15164053
Kim DS, Jung HH, Park SH, Chin H: Isolation and characterization of the 5'-upstream region of the human N-type calcium channel alpha1B subunit gene. Chromosomal localization and promoter analysis. J Biol Chem. 1997 Feb 21;272(8):5098-104. doi: 10.1074/jbc.272.8.5098.
Pubmed: 9030575
Klugbauer N, Lacinova L, Marais E, Hobom M, Hofmann F: Molecular diversity of the calcium channel alpha2delta subunit. J Neurosci. 1999 Jan 15;19(2):684-91.
Pubmed: 9880589
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Pubmed: 10766861
Hobom M, Dai S, Marais E, Lacinova L, Hofmann F, Klugbauer N: Neuronal distribution and functional characterization of the calcium channel alpha2delta-2 subunit. Eur J Neurosci. 2000 Apr;12(4):1217-26. doi: 10.1046/j.1460-9568.2000.01009.x.
Pubmed: 10762351
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Pubmed: 9628818
Escayg A, De Waard M, Lee DD, Bichet D, Wolf P, Mayer T, Johnston J, Baloh R, Sander T, Meisler MH: Coding and noncoding variation of the human calcium-channel beta4-subunit gene CACNB4 in patients with idiopathic generalized epilepsy and episodic ataxia. Am J Hum Genet. 2000 May;66(5):1531-9. doi: 10.1086/302909. Epub 2000 Apr 4.
Pubmed: 10762541
Taviaux S, Williams ME, Harpold MM, Nargeot J, Lory P: Assignment of human genes for beta 2 and beta 4 subunits of voltage-dependent Ca2+ channels to chromosomes 10p12 and 2q22-q23. Hum Genet. 1997 Aug;100(2):151-4. doi: 10.1007/pl00008704.
Pubmed: 9254841
Powers PA, Liu S, Hogan K, Gregg RG: Skeletal muscle and brain isoforms of a beta-subunit of human voltage-dependent calcium channels are encoded by a single gene. J Biol Chem. 1992 Nov 15;267(32):22967-72.
Pubmed: 1385409
Williams ME, Feldman DH, McCue AF, Brenner R, Velicelebi G, Ellis SB, Harpold MM: Structure and functional expression of alpha 1, alpha 2, and beta subunits of a novel human neuronal calcium channel subtype. Neuron. 1992 Jan;8(1):71-84. doi: 10.1016/0896-6273(92)90109-q.
Pubmed: 1309651
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Pubmed: 7916667
Allard WJ, Sigal IS, Dixon RA: Sequence of the gene encoding the human M1 muscarinic acetylcholine receptor. Nucleic Acids Res. 1987 Dec 23;15(24):10604. doi: 10.1093/nar/15.24.10604.
Pubmed: 3697105
Chapman CG, Browne MJ: Isolation of the human ml (Hml) muscarinic acetylcholine receptor gene by PCR amplification. Nucleic Acids Res. 1990 Apr 25;18(8):2191. doi: 10.1093/nar/18.8.2191.
Pubmed: 2336407
Peralta EG, Ashkenazi A, Winslow JW, Smith DH, Ramachandran J, Capon DJ: Distinct primary structures, ligand-binding properties and tissue-specific expression of four human muscarinic acetylcholine receptors. EMBO J. 1987 Dec 20;6(13):3923-9.
Pubmed: 3443095
Van Raamsdonk CD, Bezrookove V, Green G, Bauer J, Gaugler L, O'Brien JM, Simpson EM, Barsh GS, Bastian BC: Frequent somatic mutations of GNAQ in uveal melanoma and blue naevi. Nature. 2009 Jan 29;457(7229):599-602. doi: 10.1038/nature07586. Epub 2008 Dec 10.
Pubmed: 19078957
Murali R, Wiesner T, Rosenblum MK, Bastian BC: GNAQ and GNA11 mutations in melanocytomas of the central nervous system. Acta Neuropathol. 2012 Mar;123(3):457-9. doi: 10.1007/s00401-012-0948-x. Epub 2012 Feb 4.
Pubmed: 22307269
Dong Q, Shenker A, Way J, Haddad BR, Lin K, Hughes MR, McBride OW, Spiegel AM, Battey J: Molecular cloning of human G alpha q cDNA and chromosomal localization of the G alpha q gene (GNAQ) and a processed pseudogene. Genomics. 1995 Dec 10;30(3):470-75. doi: 10.1006/geno.1995.1267.
Pubmed: 8825633
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