The DOI matches its Crossref record; 12 of the 12 references it cites were found in a registry or an index.
Caffeine and Adenosine
Open accessAbstract
Caffeine causes most of its biological effects via antagonizing all types of adenosine receptors (ARs): A1, A2A, A3, and A2B and, as does adenosine, exerts effects on neurons and glial cells of all brain areas. In consequence, caffeine, when acting as an AR antagonist, is doing the opposite of activation of adenosine receptors due to removal of endogenous adenosinergic tonus. Besides AR antagonism, xanthines, including caffeine, have other biological actions: they inhibit phosphodiesterases (PDEs) (e.g., PDE1, PDE4, PDE5), promote calcium release from intracellular stores, and interfere with GABA-A receptors. Caffeine, through antagonism of ARs, affects brain functions such as sleep, cognition, learning, and memory, and modifies brain dysfunctions and diseases: Alzheimer's disease, Parkinson's disease, Huntington's disease, Epilepsy, Pain/Migraine, Depression, Schizophrenia. In conclusion, targeting approaches that involve ARs will enhance the possibilities to correct brain dysfunctions, via the universally consumed substance that is caffeine.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Fredholm, B. B., Bättig, K., Holmén, J., Nehlig, A., & Zvartau, E. E. (1999) · Pharmacological Reviews · doi:10.1016/s0031-6997(24)01396-6 · Cited by 2,624 · cited 3×
“However, in the case of caffeine, the effects seen at very low doses, achieved during normal human consumption, are mostly due to AR antagonism [2].”
InfluentialAssociation of coffee and caffeine intake with the risk of Parkinson disease
Ross, G. W. (2000) · JAMA · doi:10.1001/jama.283.20.2674 · Cited by 778
Role of neurotrophic factors in depression
CASTREN, E., VOIKAR, V, & RANTAMAKI, T. (2007) · Current Opinion in Pharmacology · doi:10.1016/j.coph.2006.08.009 · Cited by 667
Adenosine A2A, but not A1, receptors mediate the arousal effect of caffeine
Huang, Z.-L., Qu, W.-M., Eguchi, N., Chen, J.-F., Schwarzschild, M. A., Fredholm, B. B., Urade, Y., & Hayaishi, O. (2005) · Nature Neuroscience · doi:10.1038/nn1491 · Cited by 640
An Update on the Mechanisms of the Psychostimulant Effects of Caffeine
Ferré, S. (2008) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2007.05196.x · Cited by 440 · cited 2×
“Caffeine improves cognition [1]; however, it also affects sleep [3].”
Doody, R. S. (2001) · Archives of Neurology · doi:10.1001/archneur.58.3.427 · Cited by 362
The neuroprotective effects of caffeine: A prospective population study (the Three City Study)
Ritchie, K., Carrière, I., de Mendonça, A., Portet, F., Dartigues, J. F., Rouaud, O., Barberger-Gateau, P., & Ancelin, M. L. (2007) · Neurology · doi:10.1212/01.wnl.0000266670.35219.0c · Cited by 347
Association between A2a receptor gene polymorphisms and caffeine-induced anxiety
Alsene, K., Deckert, J., Sand, P., & de Wit, H. (2003) · Neuropsychopharmacology · doi:10.1038/sj.npp.1300232 · Cited by 334
Rétey, J. V., Adam, M., Khatami, R., Luhmann, U. F. O., Jung, H. H., Berger, W., & Landolt, H.-P. (2007) · Clinical Pharmacology & Therapeutics · doi:10.1038/sj.clpt.6100102 · Cited by 278
Adenosine: does it have a neuroprotective role after all?
de Mendonça, A., Sebastião, A. M., & Ribeiro, J. A. (2000) · Brain Research Reviews · doi:10.1016/s0165-0173(00)00033-3 · Cited by 248
Self-citation
Cited by
Caffeine: Cognitive and Physical Performance Enhancer or Psychoactive Drug?
Cappelletti, S., Daria, P., Sani, G., & Aromatario, M. (2015) · Current Neuropharmacology · doi:10.2174/1570159x13666141210215655 · Cited by 631
“Caffeine blocks adenosine receptors, mainly A1 and A2A subtypes, competitively antagonizing their action [40, 41] and causing an increased release of dopamine, noradrenalin, and glutamate [42, 43].”
BackgroundPsychostimulants and Cognition: A Continuum of Behavioral and Cognitive Activation
Wood, S., Sage, J. R., Shuman, T., & Anagnostaras, S. G. (2014) · Pharmacological Reviews · doi:10.1124/pr.112.007054 · Cited by 259
Effects of caffeine on sleep and cognition
Snel, J., & Lorist, M. M. (2011) · Progress in brain research · doi:10.1016/b978-0-444-53817-8.00006-2 · Cited by 187
Caffeine as a factor influencing the functioning of the human body-friend or foe?
Rodak, K., Kokot, I., & Kratz, E. M. (2021) · Nutrients · doi:10.3390/nu13093088 · Cited by 188
Adenosine receptor antagonists including caffeine alter fetal brain development in mice
Silva, C. G., Métin, C., Fazeli, W., Machado, N. J., Darmopil, S., Launay, P.-S., Ghestem, A., Nesa, M.-P., Bassot, E., Szabó, E., et al. (2013) · Science Translational Medicine · doi:10.1126/scitranslmed.3006258 · Cited by 177
Jee, H. J., Lee, S. G., Bormate, K. J., & Jung, Y.-S. (2020) · Nutrients · doi:10.3390/nu12103080 · Cited by 111
“Furthermore, caffeine is a stimulant for the central nervous system that can penetrate biological membranes, including the blood–brain barrier and placental barrier, and it maintains arousal function in the brain as a nonspecific potent inhibitor of the A1 and A2A adenosine receptors that promote drowsiness [9].”
BackgroundArab, L., Biggs, M. L., O'Meara, E. S., Longstreth, W. T., Crane, P. K., & Fitzpatrick, A. L. (2011) · Journal of Alzheimer's Disease · doi:10.3233/jad-2011-110431 · Cited by 98
Bułdak, R. J., Hejmo, T., Osowski, M., Bułdak, Ł., Kukla, M., Polaniak, R., & Birkner, E. (2018) · Molecules · doi:10.3390/molecules23123309 · Cited by 89
“Caffeine is an antagonist of phosphodiesterases [94,95] and adenosine receptors A1, A2A, and A2B [96,97], which has the effect of stimulating the central nervous system by increasing the release of dopamine, noradrenaline, and glutamate [98,99].”
BackgroundQuantum effects in the brain: A review
Adams, B., & Petruccione, F. (2020) · AVS Quantum Science · doi:10.1116/1.5135170 · Cited by 80
Shen, J. G., Brooks, M. B., Cincotta, J., & Manjourides, J. D. (2019) · Journal of Science and Medicine in Sport · doi:10.1016/j.jsams.2018.07.022 · Cited by 75
Clarke, N. D., Kornilios, E., & Richardson, D. L. (2015) · Journal of Strength and Conditioning Research · doi:10.1519/jsc.0000000000000945 · Cited by 71
Manalo, R. V. M., & Medina, P. M. B. (2018) · Frontiers in Neuroscience · doi:10.3389/fnins.2018.00137 · Cited by 55
Ruxton, C. H. S. (2014) · Journal of Human Nutrition and Dietetics · doi:10.1111/jhn.12172 · Cited by 49
Leung, C., & Wong, Y. (2017) · Molecules · doi:10.3390/molecules22071239 · Cited by 48
Jason, T., Somrat, L., Vitool, L., Wipawan, C. P., Thanapoom, R., Mahlet, G. T., Bizu, G., & Michelle, A. W. (2014) · Journal of Public Health and Epidemiology · doi:10.5897/jphe2014.0620 · Cited by 33
Central nervous system activities of extract Mangifera indica L.
López-Ríos, L., Wiebe, J. C., Vega-Morales, T., & Gericke, N. (2020) · Journal of Ethnopharmacology · doi:10.1016/j.jep.2020.112996 · Cited by 27
Silva, H., Del Coso, J., & Pickering, C. (2025) · Sports Medicine · doi:10.1007/s40279-025-02245-y · Cited by 21
Sensorimotor gating is disrupted by acute but not chronic systemic exposure to caffeine in mice
Dubroqua, S., Yee, B. K., & Singer, P. (2014) · Psychopharmacology · doi:10.1007/s00213-014-3548-8 · Cited by 10
Morales, A. P., Sampaio-Jorge, F., Barth, T., Pierucci, A. P. T. R., & Ribeiro, B. G. (2020) · Nutrients · doi:10.3390/nu12072101 · Cited by 12
Caffeine and Cardiometabolic Health: Evidence, Controversies, and Clinical Considerations
Kayikcioglu, M., & Ozkan, H. S. (2026) · Nutrition Reviews · doi:10.1093/nutrit/nuag018 · Cited by 1
Metadata
- Authors
- Ribeiro, J. A., & Sebastião, A. M.
- Venue
- Journal of Alzheimer's Disease
- Publisher
- SAGE Publications
- Published
- 2010-04-14
- Volume
- 20
- Issue
- s1
- Pages
- S3-S15
- ISSN
- 1387-2877 (ISSN-L)
- 1875-8908
- OpenAlex
- W2097533515
- Cited by
- 577
- References
- 12
- FWCI
- 13.52
- Type
- journal article
- Language
- en
- Open access
- hybrid
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
Data sources
Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.