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Pathway Description
Citalopram Metabolism Pathway
Homo sapiens
Drug Metabolism Pathway
Created: 2013-09-11
Last Updated: 2019-08-30
Citalopram is a selective serotonin reuptake inhibitor that exerts antidepressive effects by selectively inhibiting serotonin reuptake in the brain. It does so by competing for the same binding site as serotonin on the the sodium-dependent serotonin transporter (SLC6A4). This increases the concentrations of serotonin in the synaptic cleft and reverses the state of low concentration seen in depression. Higher concentration of serotonin has also been shown to have long-term neuromodulatory effects. Binding of serotonin to certain serotonin receptors activate adenylate cyclase, which produces cAMP. cAMP activates protein kinase A which activates cAMP-responsive binding protein 1 (CREB-1). CREB-1 enters the nucleus and affects transcription of brain-derived neurotrophic factor (BDNF). BDNF subsequently stimulates neurogenesis, which may contribute to the long-term reversal of depression.
References
Citalopram Pathway References
Celexa. (2009). e-CPS (online version of Compendium of Pharmaceuticals and Specialties). Retrieved December 23, 2009.
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Pubmed: 7684072
Hsu YP, Weyler W, Chen S, Sims KB, Rinehart WB, Utterback MC, Powell JF, Breakefield XO: Structural features of human monoamine oxidase A elucidated from cDNA and peptide sequences. J Neurochem. 1988 Oct;51(4):1321-4. doi: 10.1111/j.1471-4159.1988.tb03105.x.
Pubmed: 3418353
Bach AW, Lan NC, Johnson DL, Abell CW, Bembenek ME, Kwan SW, Seeburg PH, Shih JC: cDNA cloning of human liver monoamine oxidase A and B: molecular basis of differences in enzymatic properties. Proc Natl Acad Sci U S A. 1988 Jul;85(13):4934-8. doi: 10.1073/pnas.85.13.4934.
Pubmed: 3387449
Chen ZY, Hotamisligil GS, Huang JK, Wen L, Ezzeddine D, Aydin-Muderrisoglu N, Powell JF, Huang RH, Breakefield XO, Craig I, et al.: Structure of the human gene for monoamine oxidase type A. Nucleic Acids Res. 1991 Aug 25;19(16):4537-41. doi: 10.1093/nar/19.16.4537.
Pubmed: 1886775
Grimsby J, Chen K, Wang LJ, Lan NC, Shih JC: Human monoamine oxidase A and B genes exhibit identical exon-intron organization. Proc Natl Acad Sci U S A. 1991 May 1;88(9):3637-41. doi: 10.1073/pnas.88.9.3637.
Pubmed: 2023912
Chen K, Wu HF, Shih JC: The deduced amino acid sequences of human platelet and frontal cortex monoamine oxidase B are identical. J Neurochem. 1993 Jul;61(1):187-90. doi: 10.1111/j.1471-4159.1993.tb03554.x.
Pubmed: 8515265
Neumeier M, Weigert J, Schaffler A, Weiss TS, Schmidl C, Buttner R, Bollheimer C, Aslanidis C, Scholmerich J, Buechler C: Aldehyde oxidase 1 is highly abundant in hepatic steatosis and is downregulated by adiponectin and fenofibric acid in hepatocytes in vitro. Biochem Biophys Res Commun. 2006 Nov 24;350(3):731-5. doi: 10.1016/j.bbrc.2006.09.101. Epub 2006 Sep 27.
Pubmed: 17022944
Fu C, Di L, Han X, Soderstrom C, Snyder M, Troutman MD, Obach RS, Zhang H: Aldehyde oxidase 1 (AOX1) in human liver cytosols: quantitative characterization of AOX1 expression level and activity relationship. Drug Metab Dispos. 2013 Oct;41(10):1797-804. doi: 10.1124/dmd.113.053082. Epub 2013 Jul 15.
Pubmed: 23857892
Wright RM, Vaitaitis GM, Wilson CM, Repine TB, Terada LS, Repine JE: cDNA cloning, characterization, and tissue-specific expression of human xanthine dehydrogenase/xanthine oxidase. Proc Natl Acad Sci U S A. 1993 Nov 15;90(22):10690-4. doi: 10.1073/pnas.90.22.10690.
Pubmed: 8248161
Kimura S, Umeno M, Skoda RC, Meyer UA, Gonzalez FJ: The human debrisoquine 4-hydroxylase (CYP2D) locus: sequence and identification of the polymorphic CYP2D6 gene, a related gene, and a pseudogene. Am J Hum Genet. 1989 Dec;45(6):889-904.
Pubmed: 2574001
Gaedigk A, Bhathena A, Ndjountche L, Pearce RE, Abdel-Rahman SM, Alander SW, Bradford LD, Rogan PK, Leeder JS: Identification and characterization of novel sequence variations in the cytochrome P4502D6 (CYP2D6) gene in African Americans. Pharmacogenomics J. 2005;5(3):173-82. doi: 10.1038/sj.tpj.6500305.
Pubmed: 15768052
Sridar C, Snider NT, Hollenberg PF: Anandamide oxidation by wild-type and polymorphically expressed CYP2B6 and CYP2D6. Drug Metab Dispos. 2011 May;39(5):782-8. doi: 10.1124/dmd.110.036707. Epub 2011 Feb 2.
Pubmed: 21289075
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