Caffeine | DrugBank Online

Step 2

Nehlig A, Daval JL, Debry G: Caffeine and the central nervous system: mechanisms of action, biochemical, metabolic and psychostimulant effects. Brain Res Brain Res Rev. 1992 May-Aug;17(2):139-70. [PubMed:1356551] Ding R, Shi J, Pabon K, Scotto KW: Xanthines down-regulate the drug transporter ABCG2 and reverse multidrug resistance. Mol Pharmacol. 2012 Mar;81(3):328-37. doi: 10.1124/mol.111.075556. Epub 2011 Nov 23. [PubMed:22113078] Kole J, Barnhill A: Caffeine Content Labeling: A Missed Opportunity for Promoting Personal and Public Health. J Caffeine Res. 2013 Sep;3(3):108-113. doi: 10.1089/jcr.2013.0017. [PubMed:24761278] Michael Z, Spyropoulos F, Ghanta S, Christou H: Bronchopulmonary Dysplasia: An Update of Current Pharmacologic Therapies and New Approaches. Clin Med Insights Pediatr. 2018 Dec 11;12:1179556518817322. doi: 10.1177/1179556518817322. eCollection 2018. [PubMed:30574005] Collins JJP, Tibboel D, de Kleer IM, Reiss IKM, Rottier RJ: The Future of Bronchopulmonary Dysplasia: Emerging Pathophysiological Concepts and Potential New Avenues of Treatment. Front Med (Lausanne). 2017 May 22;4:61. doi: 10.3389/fmed.2017.00061. eCollection 2017. [PubMed:28589122] Lipton RB, Diener HC, Robbins MS, Garas SY, Patel K: Caffeine in the management of patients with headache. J Headache Pain. 2017 Oct 24;18(1):107. doi: 10.1186/s10194-017-0806-2. [PubMed:29067618] Schneider E, Freundlieb S, Tapio S, Boos W: Molecular characterization of the MalT-dependent periplasmic alpha-amylase of Escherichia coli encoded by malS. J Biol Chem. 1992 Mar 15;267(8):5148-54. [PubMed:1544897] Cappelletti S, Piacentino D, Sani G, Aromatario M: Caffeine: cognitive and physical performance enhancer or psychoactive drug? Curr Neuropharmacol. 2015 Jan;13(1):71-88. doi: 10.2174/1570159X13666141210215655. [PubMed:26074744] Boswell-Smith V, Spina D, Page CP: Phosphodiesterase inhibitors. Br J Pharmacol. 2006 Jan;147 Suppl 1:S252-7. doi: 10.1038/sj.bjp.0706495. [PubMed:16402111] White JR Jr, Padowski JM, Zhong Y, Chen G, Luo S, Lazarus P, Layton ME, McPherson S: Pharmacokinetic analysis and comparison of caffeine administered rapidly or slowly in coffee chilled or hot versus chilled energy drink in healthy young adults. Clin Toxicol (Phila). 2016;54(4):308-12. doi: 10.3109/15563650.2016.1146740. [PubMed:27100333] Mandel HG: Update on caffeine consumption, disposition and action. Food Chem Toxicol. 2002 Sep;40(9):1231-4. doi: 10.1016/s0278-6915(02)00093-5. [PubMed:12204386] Justin Evans; Amanda S. Battisti (2019). Caffeine. Stat Pearls Publishing. IARC Working Group on the Evaluation of Carcinogenic Risk to Humans (1991). Coffee, Tea, Mate, Methylxanthines and Methylglyoxal. International Agency for Research on Cancer. Institute of Medicine (US) Committee on Military Nutrition Research. (2001). Caffeine for the Sustainment of Mental Task Performance: Formulations for Military Operations.. National Academic Press. Highly Concentrated Caffeine in Dietary Supplements: Guidance for Industry [Link] Caffeine citrate injection FDA label [Link] DailyMed Search: Caffeine [Link] PDB reference [Link] FDA approval [Link] Alcohol and Drug Foundation, Australia [Link] Migergot, DailyMed [Link] Caffeine pathway: Pharm GKB [Link] Caffeine and sodium benzoate injection [Link]

Step 3

Gaytan SP, Saadani-Makki F, Bodineau L, Frugiere A, Larnicol N, Pasaro R: Effect of postnatal exposure to caffeine on the pattern of adenosine A1 receptor distribution in respiration-related nuclei of the rat brainstem. Auton Neurosci. 2006 Jun 30;126-127:339-46. Epub 2006 May 15. [PubMed:16702031] Wang SJ: Caffeine facilitation of glutamate release from rat cerebral cortex nerve terminals (synaptosomes) through activation protein kinase C pathway: an interaction with presynaptic adenosine A1 receptors. Synapse. 2007 Jun;61(6):401-11. [PubMed:17372967] Rieg T, Schnermann J, Vallon V: Adenosine A1 receptors determine effects of caffeine on total fluid intake but not caffeine appetite. Eur J Pharmacol. 2007 Jan 26;555(2-3):174-7. Epub 2006 Oct 25. [PubMed:17126319] Mustafa S, Venkatesh P, Pasha K, Mullangi R, Srinivas NR: Altered intravenous pharmacokinetics of topotecan in rats with acute renal failure (ARF) induced by uranyl nitrate: do adenosine A1 antagonists (selective/non-selective) normalize the altered topotecan kinetics in ARF? Xenobiotica. 2006 Dec;36(12):1239-58. [PubMed:17162470] Listos J, Malec D, Fidecka S: Adenosine receptor antagonists intensify the benzodiazepine withdrawal signs in mice. Pharmacol Rep. 2006 Sep-Oct;58(5):643-51. [PubMed:17085856] Caffeine citrate injection FDA label [Link]

Step 4

Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284] Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423] Daly JW: Caffeine analogs: biomedical impact. Cell Mol Life Sci. 2007 Aug;64(16):2153-69. [PubMed:17514358]

Step 5

Riksen NP, Franke B, van den Broek P, Smits P, Rongen GA: The 1976C>T polymorphism in the adenosine A2A receptor gene does not affect the vasodilator response to adenosine in humans in vivo. Pharmacogenet Genomics. 2007 Jul;17(7):551-4. [PubMed:17558310] Zhao G, Messina E, Xu X, Ochoa M, Sun HL, Leung K, Shryock J, Belardinelli L, Hintze TH: Caffeine attenuates the duration of coronary vasodilation and changes in hemodynamics induced by regadenoson (CVT-3146), a novel adenosine A2A receptor agonist. J Cardiovasc Pharmacol. 2007 Jun;49(6):369-75. [PubMed:17577101] Cornelis MC, El-Sohemy A, Campos H: Genetic polymorphism of the adenosine A2A receptor is associated with habitual caffeine consumption. Am J Clin Nutr. 2007 Jul;86(1):240-4. [PubMed:17616786] Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]

Step 6

Daly JW: Caffeine analogs: biomedical impact. Cell Mol Life Sci. 2007 Aug;64(16):2153-69. [PubMed:17514358]

Step 7

Ribeiro JA, Sebastiao AM: Caffeine and adenosine. J Alzheimers Dis. 2010;20 Suppl 1:S3-15. doi: 10.3233/JAD-2010-1379. [PubMed:20164566] Essayan DM: Cyclic nucleotide phosphodiesterases. J Allergy Clin Immunol. 2001 Nov;108(5):671-80. [PubMed:11692087]

Step 8

Foukas LC, Daniele N, Ktori C, Anderson KE, Jensen J, Shepherd PR: Direct effects of caffeine and theophylline on p110 delta and other phosphoinositide 3-kinases. Differential effects on lipid kinase and protein kinase activities. J Biol Chem. 2002 Oct 4;277(40):37124-30. Epub 2002 Jul 26. [PubMed:12145276]

Step 9

Foukas LC, Daniele N, Ktori C, Anderson KE, Jensen J, Shepherd PR: Direct effects of caffeine and theophylline on p110 delta and other phosphoinositide 3-kinases. Differential effects on lipid kinase and protein kinase activities. J Biol Chem. 2002 Oct 4;277(40):37124-30. Epub 2002 Jul 26. [PubMed:12145276]

Step 10

Foukas LC, Daniele N, Ktori C, Anderson KE, Jensen J, Shepherd PR: Direct effects of caffeine and theophylline on p110 delta and other phosphoinositide 3-kinases. Differential effects on lipid kinase and protein kinase activities. J Biol Chem. 2002 Oct 4;277(40):37124-30. Epub 2002 Jul 26. [PubMed:12145276]

Step 11

Foukas LC, Daniele N, Ktori C, Anderson KE, Jensen J, Shepherd PR: Direct effects of caffeine and theophylline on p110 delta and other phosphoinositide 3-kinases. Differential effects on lipid kinase and protein kinase activities. J Biol Chem. 2002 Oct 4;277(40):37124-30. Epub 2002 Jul 26. [PubMed:12145276]

Step 12

Parker I, Ivorra I: Caffeine inhibits inositol trisphosphate-mediated liberation of intracellular calcium in Xenopus oocytes. J Physiol. 1991 Feb;433:229-40. [PubMed:1844813]

Step 13

Sarkaria JN, Busby EC, Tibbetts RS, Roos P, Taya Y, Karnitz LM, Abraham RT: Inhibition of ATM and ATR kinase activities by the radiosensitizing agent, caffeine. Cancer Res. 1999 Sep 1;59(17):4375-82. [PubMed:10485486] Blasina A, Price BD, Turenne GA, McGowan CH: Caffeine inhibits the checkpoint kinase ATM. Curr Biol. 1999 Oct 7;9(19):1135-8. [PubMed:10531013]

Step 14

Ribeiro JA, Sebastiao AM: Caffeine and adenosine. J Alzheimers Dis. 2010;20 Suppl 1:S3-15. doi: 10.3233/JAD-2010-1379. [PubMed:20164566] Justin Evans; Amanda S. Battisti (2019). Caffeine. Stat Pearls Publishing.

Step 15

Ribeiro JA, Sebastiao AM: Caffeine and adenosine. J Alzheimers Dis. 2010;20 Suppl 1:S3-15. doi: 10.3233/JAD-2010-1379. [PubMed:20164566] Justin Evans; Amanda S. Battisti (2019). Caffeine. Stat Pearls Publishing.

Step 16

Boswell-Smith V, Spina D, Page CP: Phosphodiesterase inhibitors. Br J Pharmacol. 2006 Jan;147 Suppl 1:S252-7. doi: 10.1038/sj.bjp.0706495. [PubMed:16402111] Howell LL: Comparative effects of caffeine and selective phosphodiesterase inhibitors on respiration and behavior in rhesus monkeys. J Pharmacol Exp Ther. 1993 Aug;266(2):894-903. [PubMed:7689104] Caffeine citrate injection FDA label [Link]

Step 17

Brosen K: Drug interactions and the cytochrome P450 system. The role of cytochrome P450 1A2. Clin Pharmacokinet. 1995;29 Suppl 1:20-5. [PubMed:8846619] Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. [PubMed:19515014] Hickman D, Wang JP, Wang Y, Unadkat JD: Evaluation of the selectivity of In vitro probes and suitability of organic solvents for the measurement of human cytochrome P450 monooxygenase activities. Drug Metab Dispos. 1998 Mar;26(3):207-15. [PubMed:9492382] Hartter S, Nordmark A, Rose DM, Bertilsson L, Tybring G, Laine K: Effects of caffeine intake on the pharmacokinetics of melatonin, a probe drug for CYP1A2 activity. Br J Clin Pharmacol. 2003 Dec;56(6):679-82. [PubMed:14616429] Gu L, Gonzalez FJ, Kalow W, Tang BK: Biotransformation of caffeine, paraxanthine, theobromine and theophylline by cDNA-expressed human CYP1A2 and CYP2E1. Pharmacogenetics. 1992 Apr;2(2):73-7. [PubMed:1302044] Flockhart Table of Drug Interactions [Link] Caffeine citrate injection FDA label [Link]

Step 18

Kot M, Daniel WA: Effect of cytochrome P450 (CYP) inducers on caffeine metabolism in the rat. Pharmacol Rep. 2007 May-Jun;59(3):296-305. [PubMed:17652830] Flockhart Table of Drug Interactions [Link]

Step 19

Collom SL, Jamakhandi AP, Tackett AJ, Radominska-Pandya A, Miller GP: CYP2E1 active site residues in substrate recognition sequence 5 identified by photoaffinity labeling and homology modeling. Arch Biochem Biophys. 2007 Mar 1;459(1):59-69. doi: 10.1016/j.abb.2006.10.028. Epub 2006 Nov 2. [PubMed:17222385] Fuhr U, Rost KL, Engelhardt R, Sachs M, Liermann D, Belloc C, Beaune P, Janezic S, Grant D, Meyer UA, Staib AH: Evaluation of caffeine as a test drug for CYP1A2, NAT2 and CYP2E1 phenotyping in man by in vivo versus in vitro correlations. Pharmacogenetics. 1996 Apr;6(2):159-76. [PubMed:9156694] Gu L, Gonzalez FJ, Kalow W, Tang BK: Biotransformation of caffeine, paraxanthine, theobromine and theophylline by cDNA-expressed human CYP1A2 and CYP2E1. Pharmacogenetics. 1992 Apr;2(2):73-7. [PubMed:1302044]

Step 20

Thorn CF, Aklillu E, McDonagh EM, Klein TE, Altman RB: PharmGKB summary: caffeine pathway. Pharmacogenet Genomics. 2012 May;22(5):389-95. doi: 10.1097/FPC.0b013e3283505d5e. [PubMed:22293536] Kot M, Daniel WA: The relative contribution of human cytochrome P450 isoforms to the four caffeine oxidation pathways: an in vitro comparative study with cDNA-expressed P450s including CYP2C isoforms. Biochem Pharmacol. 2008 Aug 15;76(4):543-51. doi: 10.1016/j.bcp.2008.05.025. Epub 2008 Jul 9. [PubMed:18619574] Kot M, Daniel WA: Caffeine as a marker substrate for testing cytochrome P450 activity in human and rat. Pharmacol Rep. 2008 Nov-Dec;60(6):789-97. [PubMed:19211970]

Step 21

Zhou SF, Zhou ZW, Yang LP, Cai JP: Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675. Epub 2009 Sep 1. [PubMed:19515014] Utoh M, Murayama N, Uno Y, Onose Y, Hosaka S, Fujino H, Shimizu M, Iwasaki K, Yamazaki H: Monkey liver cytochrome P450 2C9 is involved in caffeine 7-N-demethylation to form theophylline. Xenobiotica. 2013 Dec;43(12):1037-42. doi: 10.3109/00498254.2013.793874. Epub 2013 May 16. [PubMed:23679834] Kot M, Daniel WA: The relative contribution of human cytochrome P450 isoforms to the four caffeine oxidation pathways: an in vitro comparative study with cDNA-expressed P450s including CYP2C isoforms. Biochem Pharmacol. 2008 Aug 15;76(4):543-51. doi: 10.1016/j.bcp.2008.05.025. Epub 2008 Jul 9. [PubMed:18619574]

Step 22

Tassaneeyakul W, Birkett DJ, Veronese ME, McManus ME, Tukey RH, Quattrochi LC, Gelboin HV, Miners JO: Specificity of substrate and inhibitor probes for human cytochromes P450 1A1 and 1A2. J Pharmacol Exp Ther. 1993 Apr;265(1):401-7. [PubMed:8474022]

Step 23

Shimada T, Gillam EM, Sutter TR, Strickland PT, Guengerich FP, Yamazaki H: Oxidation of xenobiotics by recombinant human cytochrome P450 1B1. Drug Metab Dispos. 1997 May;25(5):617-22. [PubMed:9152602]

Step 24

Ha HR, Chen J, Krahenbuhl S, Follath F: Biotransformation of caffeine by cDNA-expressed human cytochromes P-450. Eur J Clin Pharmacol. 1996;49(4):309-15. doi: 10.1007/bf00226333. [PubMed:8857078] Ozdemir V, Naranjo CA, Shulman RW, Herrmann N, Sellers EM, Reed K, Kalow W: Determinants of interindividual variability and extent of CYP2D6 and CYP1A2 inhibition by paroxetine and fluvoxamine in vivo. J Clin Psychopharmacol. 1998 Jun;18(3):198-207. [PubMed:9617978]

Step 25

Ding R, Shi J, Pabon K, Scotto KW: Xanthines down-regulate the drug transporter ABCG2 and reverse multidrug resistance. Mol Pharmacol. 2012 Mar;81(3):328-37. doi: 10.1124/mol.111.075556. Epub 2011 Nov 23. [PubMed:22113078]