Adenosine A2A receptor antagonists: from caffeine to selective non‐xanthines

A long evolution of knowledge of the psychostimulant caffeine led in the 1960s to another purine natural product, adenosine and its A2A receptor. Adenosine is a short‐lived autocrine/paracrine mediator that acts pharmacologically at four different adenosine receptors in a manner opposite to the pan‐...

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Published inBritish journal of pharmacology Vol. 179; no. 14; pp. 3496 - 3511
Main Authors Jacobson, Kenneth A., Gao, Zhan‐Guo, Matricon, Pierre, Eddy, Matthew T., Carlsson, Jens
Format Journal Article
LanguageEnglish
Published London Blackwell Publishing Ltd 01.07.2022
Subjects
Adenosine
Adenosine A2A receptors
Aging
Autocrine signalling
Caffeine
Clinical trials
Diabetes mellitus
Drug development
Immunotherapy
Liver diseases
Membrane proteins
Natural products
Neurodegenerative diseases
Paracrine signalling
Xanthines
Online AccessGet full text
ISSN0007-1188
1476-5381
1476-5381
DOI10.1111/bph.15103

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Abstract A long evolution of knowledge of the psychostimulant caffeine led in the 1960s to another purine natural product, adenosine and its A2A receptor. Adenosine is a short‐lived autocrine/paracrine mediator that acts pharmacologically at four different adenosine receptors in a manner opposite to the pan‐antagonist caffeine and serves as an endogenous allostatic regulator. Although detrimental in the developing brain, caffeine appears to be cerebroprotective in aging. Moderate caffeine consumption in adults, except in pregnancy, may also provide benefit in pain, diabetes, and kidney and liver disorders. Inhibition of A2A receptors is one of caffeine's principal effects and we now understand this interaction at the atomic level. The A2A receptor has become a prototypical example of utilizing high‐resolution structures of GPCRs for the rational design of chemically diverse drug molecules. The previous focus on discovery of selective A2A receptor antagonists for neurodegenerative diseases has expanded to include immunotherapy for cancer, and clinical trials have ensued. LINKED ARTICLES This article is part of a themed issue on Structure Guided Pharmacology of Membrane Proteins (BJP 75th Anniversary). To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v179.14/issuetoc
AbstractList A long evolution of knowledge of the psychostimulant caffeine led in the 1960s to another purine natural product, adenosine and its A2A receptor. Adenosine is a short-lived autocrine/paracrine mediator that acts pharmacologically at four different adenosine receptors in a manner opposite to the pan-antagonist caffeine and serves as an endogenous allostatic regulator. Although detrimental in the developing brain, caffeine appears to be cerebroprotective in aging. Moderate caffeine consumption in adults, except in pregnancy, may also provide benefit in pain, diabetes, and kidney and liver disorders. Inhibition of A2A receptors is one of caffeine's principal effects and we now understand this interaction at the atomic level. The A2A receptor has become a prototypical example of utilizing high-resolution structures of GPCRs for the rational design of chemically diverse drug molecules. The previous focus on discovery of selective A2A receptor antagonists for neurodegenerative diseases has expanded to include immunotherapy for cancer, and clinical trials have ensued. LINKED ARTICLES: This article is part of a themed issue on Structure Guided Pharmacology of Membrane Proteins (BJP 75th Anniversary). To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v179.14/issuetoc.A long evolution of knowledge of the psychostimulant caffeine led in the 1960s to another purine natural product, adenosine and its A2A receptor. Adenosine is a short-lived autocrine/paracrine mediator that acts pharmacologically at four different adenosine receptors in a manner opposite to the pan-antagonist caffeine and serves as an endogenous allostatic regulator. Although detrimental in the developing brain, caffeine appears to be cerebroprotective in aging. Moderate caffeine consumption in adults, except in pregnancy, may also provide benefit in pain, diabetes, and kidney and liver disorders. Inhibition of A2A receptors is one of caffeine's principal effects and we now understand this interaction at the atomic level. The A2A receptor has become a prototypical example of utilizing high-resolution structures of GPCRs for the rational design of chemically diverse drug molecules. The previous focus on discovery of selective A2A receptor antagonists for neurodegenerative diseases has expanded to include immunotherapy for cancer, and clinical trials have ensued. LINKED ARTICLES: This article is part of a themed issue on Structure Guided Pharmacology of Membrane Proteins (BJP 75th Anniversary). To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v179.14/issuetoc.
A long evolution of knowledge of the psychostimulant caffeine led in the 1960s to another purine natural product, adenosine and its A 2A receptor. Adenosine is a short-lived autocrine/paracrine mediator that acts pharmacologically at four different adenosine receptors in a manner opposite to the pan-antagonist caffeine and serves as an endogenous allostatic regulator. Although detrimental in the developing brain, caffeine appears to be cerebroprotective in aging. Moderate caffeine consumption in adults, except in pregnancy, may also provide benefit in pain, diabetes, and kidney and liver disorders. Inhibition of A 2A receptors is one of caffeine’s principal effects and we now understand this interaction at the atomic level. The A 2A receptor has become a prototypical example of utilizing high-resolution structures of GPCRs for the rational design of chemically diverse drug molecules. The previous focus on discovery of selective A 2A receptor antagonists for neurodegenerative diseases has expanded to include immunotherapy for cancer, and clinical trials have ensued.
A long evolution of knowledge of the psychostimulant caffeine led in the 1960s to another purine natural product, adenosine and its A2A receptor. Adenosine is a short‐lived autocrine/paracrine mediator that acts pharmacologically at four different adenosine receptors in a manner opposite to the pan‐antagonist caffeine and serves as an endogenous allostatic regulator. Although detrimental in the developing brain, caffeine appears to be cerebroprotective in aging. Moderate caffeine consumption in adults, except in pregnancy, may also provide benefit in pain, diabetes, and kidney and liver disorders. Inhibition of A2A receptors is one of caffeine's principal effects and we now understand this interaction at the atomic level. The A2A receptor has become a prototypical example of utilizing high‐resolution structures of GPCRs for the rational design of chemically diverse drug molecules. The previous focus on discovery of selective A2A receptor antagonists for neurodegenerative diseases has expanded to include immunotherapy for cancer, and clinical trials have ensued. LINKED ARTICLES This article is part of a themed issue on Structure Guided Pharmacology of Membrane Proteins (BJP 75th Anniversary). To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v179.14/issuetoc
A long evolution of knowledge of the psychostimulant caffeine led in the 1960s to another purine natural product, adenosine and its A2A receptor. Adenosine is a short‐lived autocrine/paracrine mediator that acts pharmacologically at four different adenosine receptors in a manner opposite to the pan‐antagonist caffeine and serves as an endogenous allostatic regulator. Although detrimental in the developing brain, caffeine appears to be cerebroprotective in aging. Moderate caffeine consumption in adults, except in pregnancy, may also provide benefit in pain, diabetes, and kidney and liver disorders. Inhibition of A2A receptors is one of caffeine's principal effects and we now understand this interaction at the atomic level. The A2A receptor has become a prototypical example of utilizing high‐resolution structures of GPCRs for the rational design of chemically diverse drug molecules. The previous focus on discovery of selective A2A receptor antagonists for neurodegenerative diseases has expanded to include immunotherapy for cancer, and clinical trials have ensued.LINKED ARTICLESThis article is part of a themed issue on Structure Guided Pharmacology of Membrane Proteins (BJP 75th Anniversary). To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v179.14/issuetoc
Author Eddy, Matthew T.
Jacobson, Kenneth A.
Gao, Zhan‐Guo
Carlsson, Jens
Matricon, Pierre
AuthorAffiliation 2 Department of Cell and Molecular Biology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden
1 Molecular Recognition Section, Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA
3 Department of Chemistry, University of Florida, Gainesville, FL, USA
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References 2019; 91
1965; 148
1958; 232
2019; 95
2012; 366
2013; 67
2019; 10
2019; 13
2018; 201
2002; 277
2002; 99
1999; 47
1968; 6
2019; 17
2019; 18
2011; 54
2020; 10
2014; 28
2013; 5
1979; 33
2018; 43
2019; 166
2011; 474
2012; 96
2018; 46
2018; 7
1997; 388
2018; 9
2018; 8
2013; 58
2010; 1
2018; 172
2018; 4
1995; 25
2019; 23
2013; 53
1957; 231
2019; 27
1999; 51
2010; 3
2007; 64
2017; 167
2017; 321
2018; 38
2018; 36
1981; 78
1990; 173
2010; 33
2019; 9
1993; 45
2019; 5
2019; 37
2013; 93
2020; 35
1969; 16
2019; 109
2011; 493
1929; 68
2018; 26
2019; 186
2016; 11
2018; 19
2018; 18
2016; 7
2016; 1
1989; 244
2018; 117
2017; 58
2015; 112
2018; 115
2016; 21
1986; 29
2014; 39
2018; 12
2014; 264
2019; 294
2018; 99
2018; 10
2007; 318
2019; 176
1982; 12
2017; 6
2017; 7
2010; 53
2017; 8
2004; 64
1970; 6
1989; 86
2020; 63
2019; 126
2013; 169
2016; 104
2011; 19
2012; 55
2017; 114
2017; 117
2017; 30
2009; 52
2006; 61
2000; 289
2017; 36
2015; 40
1980; 77
2000; 283
2018; 72
2018; 78
2012; 337
2016; 89
2018; 140
1963; 22
2015; 18
2017; 2017
2017; 25
2017; 23
2016; 54
2018; 61
2008; 322
2016; 59
2011; 332
2019; 142
1993; 13
1982; 81
1967; 170
2020
2018; 558
2019
2018
2009; 8
2016; 139
2016; 533
2012; 7
2007; 46
2011; 100
1920; 16
2019; 132
2019; 253
References_xml – volume: 186
  start-page: 172789
  year: 2019
  article-title: Caffeine modulates voluntary alcohol intake in mice depending on the access conditions: Involvement of adenosine receptors and the role of individual differences
  publication-title: Pharmacology, Biochemistry, and Behavior
– volume: 7
  start-page: 2064
  issue: 12
  year: 2012
  end-page: 2073
  article-title: Fragment screening of GPCRs using biophysical methods: Identification of ligands of the adenosine A receptor with novel biological activity
  publication-title: ACS Chemical Biology
– volume: 19
  start-page: 1283
  year: 2011
  end-page: 1293
  article-title: Structure of the adenosine A receptor in complex with ZM241385 and the xanthines XAC and caffeine
  publication-title: Structure
– volume: 25
  start-page: 1275
  issue: 8
  year: 2017
  end-page: 1285
  article-title: Structures of human A and A adenosine receptors with xanthines reveal determinants of selectivity
  publication-title: Structure
– volume: 95
  start-page: 34
  year: 2019
  end-page: 41
  article-title: Purinergic signalling and brain development
  publication-title: Seminars in Cell & Developmental Biology
– volume: 109
  start-page: 635
  issue: 3
  year: 2019
  end-page: 647
  article-title: Coffee consumption and plasma biomarkers of metabolic and inflammatory pathways in US health professionals
  publication-title: The American Journal of Clinical Nutrition
– volume: 3
  start-page: 725
  issue: 3
  year: 2010
  end-page: 747
  article-title: Theophylline
  publication-title: Pharmaceuticals (Basel)
– volume: 89
  start-page: 485
  issue: 5
  year: 2016
  end-page: 491
  article-title: Molecular basis of ligand dissociation from the adenosine A receptor
  publication-title: Molecular Pharmacology
– volume: 10
  start-page: 925
  year: 2019
  article-title: Targeting adenosine in cancer immunotherapy to enhance T‐cell function
  publication-title: Frontiers in Immunology
– volume: 6
  year: 2017
  article-title: Ligand modulation of sidechain dynamics in a wild‐type human GPCR
  publication-title: eLife
– volume: 115
  start-page: 12,733
  year: 2018
  end-page: 12,738
  article-title: A adenosine receptor functional states characterized by F‐NMR
  publication-title: Proceedings of the National Academy of Sciences of the United States of America
– volume: 8
  start-page: 455
  year: 2009
  end-page: 463
  article-title: Community‐wide assessment of GPCR structure modelling and ligand docking: GPCR Dock 2008
  publication-title: Nature Reviews. Drug Discovery
– volume: 264
  start-page: 116
  year: 2014
  end-page: 125
  article-title: Caffeine neuroprotective effects on 6‐OHDA‐lesioned rats are mediated by several factors, including pro‐inflammatory cytokines and histone deacetylase inhibitions
  publication-title: Behavioural Brain Research
– volume: 7
  start-page: 6398
  year: 2017
  article-title: Fragment optimization by molecular dynamics free energy calculations for GPCRs: Probing druggable subpockets of the A adenosine receptor binding site
  publication-title: Scientific Reports
– volume: 9
  start-page: 547
  year: 2018
  article-title: Caffeine consumption and mortality in diabetes: An analysis of NHANES 1999–2010
  publication-title: Frontiers in Endocrinology
– volume: 53
  start-page: 2701
  issue: 10
  year: 2013
  end-page: 2714
  article-title: Complementarity between in silico and biophysical screening approaches in fragment‐based lead discovery against the A adenosine receptor
  publication-title: Journal of Chemical Information and Modeling
– volume: 46
  start-page: 430
  year: 2007
  end-page: 435
  article-title: Coffee drinking and hepatocellular carcinoma risk: A meta‐analysis
  publication-title: Hepatology
– volume: 47
  start-page: 45
  year: 1999
  end-page: 53
  article-title: 1,3‐Dialkylxanthine derivatives having high potency as antagonists at human A adenosine receptors
  publication-title: Drug Development Research
– volume: 166
  start-page: 313
  year: 2019
  end-page: 321
  article-title: The physiological effects of caffeine on synaptic transmission and plasticity in the mouse hippocampus selectively depend on adenosine A and A receptors
  publication-title: Biochemical Pharmacology
– volume: 126
  start-page: 455
  year: 2019
  end-page: 471
  article-title: Adenosine heteroreceptor complexes in the basal ganglia are implicated in Parkinson's disease and its treatment
  publication-title: Journal of Neural Transmission
– volume: 277
  start-page: 37124
  year: 2002
  end-page: 37130
  article-title: Direct effects of caffeine and theophylline on p110 delta and other phosphoinositide 3‐kinases. Differential Effects on Lipid Kinase and Protein Kinase Activities
  publication-title: The Journal of Biological Chemistry
– volume: 35
  start-page: 321
  issue: 3
  year: 2020
  end-page: 328
  article-title: C‐caffeine breath test identifies single nucleotide polymorphisms associated with caffeine metabolism
  publication-title: Drug Metabolism and Pharmacokinetics
– volume: 38
  start-page: 5
  year: 2018
  end-page: 56
  article-title: Potential therapeutic applications of adenosine A receptor ligands and opportunities for A receptor imaging
  publication-title: Medicinal Research Reviews
– volume: 10
  start-page: 1772
  issue: 11
  year: 2018
  article-title: Caffeine in the diet: Country‐level consumption and guidelines
  publication-title: Nutrients
– volume: 140
  start-page: 8228
  year: 2018
  end-page: 8235
  article-title: Extrinsic tryptophans as NMR probes of allosteric coupling in membrane proteins: Application to the A adenosine receptor
  publication-title: Journal of the American Chemical Society
– volume: 64
  start-page: 2153
  year: 2007
  end-page: 2169
  article-title: Caffeine analogues: Biomedical impact
  publication-title: Cellular and Molecular Life Sciences
– volume: 11
  issue: 11
  year: 2016
  article-title: A adenosine receptor antagonism reverts the blood‐brain barrier dysfunction induced by sleep restriction
  publication-title: PLoS ONE
– volume: 176
  start-page: S142
  year: 2019
  end-page: S228
  article-title: THE CONCISE GUIDE TO PHARMACOLOGY 2019/20: Ion channels
  publication-title: British Journal of Pharmacology
– volume: 53
  start-page: 1700
  year: 2013
  end-page: 1713
  article-title: Water network perturbation in ligand binding: Adenosine A antagonists as a case study
  publication-title: Journal of Chemical Information and Modeling
– volume: 6
  start-page: 13
  issue: 1
  year: 1970
  end-page: 23
  article-title: The effect of adenosine and adenine nucleotides on the cyclic adenosine 3′, 5′‐phosphate content of guinea pig cerebral cortex slices
  publication-title: Molecular Pharmacology
– year: 2019
– volume: 53
  start-page: 3748
  year: 2010
  end-page: 3755
  article-title: Structure‐based discovery of A adenosine receptor ligands
  publication-title: Journal of Medicinal Chemistry
– volume: 493
  start-page: 115
  year: 2011
  end-page: 136
  article-title: Fragment screening of stabilized G‐protein‐coupled receptors using biophysical methods
  publication-title: Methods in Enzymology
– volume: 30
  start-page: 271
  issue: 4
  year: 2017
  end-page: 277
  article-title: The relationship between caffeine intake and immunological and virological markers of HIV disease progression in Miami adult studies on HIV cohort
  publication-title: Viral Immunology
– volume: 55
  start-page: 1898
  issue: 5
  year: 2012
  end-page: 1903
  article-title: Discovery of 1,2,4‐triazine derivatives as adenosine A antagonists using structure based drug design
  publication-title: Journal of Medicinal Chemistry
– volume: 170
  start-page: 249
  year: 1967
  end-page: 255
  article-title: Interaction between caffeine and adenosine on calcium exchangeability in mammalian atria
  publication-title: Arch Intern Pharmacodyn
– volume: 18
  start-page: 59
  year: 2019
  end-page: 82
  article-title: GPCR drug discovery: integrating solution NMR data with crystal and cryo‐EM structures
  publication-title: Nature Reviews Drug Discovery
– volume: 7
  start-page: 12678
  year: 2017
  article-title: Adenosine A receptor mediates hypnotic effects of ethanol in mice
  publication-title: Scientific Reports
– volume: 25
  start-page: 366
  year: 1995
  end-page: 428
  article-title: Integrated methods for the construction of three dimensional models and computational probing of structure function relations in G protein‐coupled receptors
  publication-title: Methods Neurosci
– volume: 36
  start-page: 279
  year: 2017
  end-page: 285
  article-title: Methotrexate intolerance in the treatment of rheumatoid arthritis (RA): Effect of adding caffeine to the management regimen
  publication-title: Clinical Rheumatology
– volume: 6
  start-page: 167
  year: 1968
  end-page: 168
  article-title: Factors influencing the accumulation of adenosine 3', 5'‐phosphate (cyclic AMP) in brain tissue
  publication-title: Proc Internat Union Physiol Sci
– volume: 22
  start-page: 308
  year: 1963
  article-title: Antagonism of the vasodepressor effect of ATP by caffeine
  publication-title: Federation Proceedings
– volume: 321
  start-page: 8
  year: 2017
  end-page: 17
  article-title: Adenosine A receptor deletion affects social behaviors and anxiety in mice: Involvement of anterior cingulate cortex and amygdala
  publication-title: Behavioural Brain Research
– volume: 29
  start-page: 331
  issue: 4
  year: 1986
  end-page: 346
  article-title: Characterization of the A adenosine receptor labeled by [ H]NECA in rat striatal membranes
  publication-title: Molecular Pharmacology
– volume: 91
  start-page: 8162
  year: 2019
  end-page: 8169
  article-title: Accelerating the throughput of affinity mass spectrometry‐based ligand screening towards a G protein‐coupled receptor
  publication-title: Analytical Chemistry
– volume: 39
  start-page: 233
  year: 2014
  end-page: 244
  article-title: Allosteric sodium in class A GPCR signaling
  publication-title: Trends in Biochemical Sciences
– volume: 167
  start-page: 236
  issue: 4
  year: 2017
  end-page: 247
  article-title: Coffee drinking and mortality in 10 European countries: A multinational cohort study
  publication-title: Annals of Internal Medicine
– volume: 58
  start-page: 179
  year: 2013
  end-page: 182
  article-title: Association between caffeine intake and age at onset in Huntington's disease
  publication-title: Neurobiology of Disease
– volume: 53
  start-page: 1799
  issue: 4
  year: 2010
  end-page: 1809
  article-title: Structure‐based discovery of novel chemotypes for adenosine A receptor antagonists
  publication-title: Journal of Medicinal Chemistry
– volume: 7
  year: 2018
  article-title: Cryo‐EM structure of the adenosine A receptor coupled to an engineered heterotrimeric G protein
  publication-title: eLife
– volume: 10
  start-page: 162
  year: 2019
  article-title: Adenosine A receptor stimulation inhibits TCR‐induced Notch1 activation in CD8+T‐cells
  publication-title: Frontiers in Immunology
– volume: 93
  start-page: 283
  issue: 7
  year: 2013
  end-page: 287
  article-title: The interactions of caffeine with monoamine oxidase
  publication-title: Life Sciences
– volume: 283
  start-page: 2674
  issue: 20
  year: 2000
  end-page: 2679
  article-title: Association of coffee and caffeine intake with the risk of Parkinson disease
  publication-title: JAMA
– volume: 322
  start-page: 1211
  issue: 5905
  year: 2008
  end-page: 1217
  article-title: The 2.6 Angstrom Crystal Structure of a Human A2A Adenosine Receptor Bound to an Antagonist
  publication-title: Science
– volume: 28
  start-page: 830
  issue: 9
  year: 2014
  end-page: 836
  article-title: Ostracising caffeine from the pharmacological arsenal for attention‐deficit hyperactivity disorder—Was this a correct decision? A literature review
  publication-title: Journal of Psychopharmacology
– volume: 1
  start-page: 160
  year: 2010
  end-page: 164
  article-title: Hydration site thermodynamics explain SARs for triazolylpurines analogues binding to the A receptor
  publication-title: ACS Medicinal Chemistry Letters
– volume: 33
  start-page: 999
  issue: 5
  year: 1979
  end-page: 1005
  article-title: Adenosine regulates via two different types of receptors, the accumulation of cyclic AMP in cultured brain cells
  publication-title: Journal of Neurochemistry
– volume: 173
  start-page: 1169
  issue: 3
  year: 1990
  end-page: 1178
  article-title: RDC8 codes for an adenosine A receptor with physiological constitutive activity
  publication-title: Biochemical and Biophysical Research Communications
– volume: 81
  start-page: 673
  issue: 4
  year: 1982
  end-page: 676
  article-title: Xanthine derivatives as adenosine receptor antagonists
  publication-title: European Journal of Pharmacology
– volume: 58
  start-page: 94
  year: 2017
  end-page: 102
  article-title: Caffeine for apnea of prematurity: Effects on the developing brain
  publication-title: Neurotoxicology
– volume: 36
  start-page: 9089
  issue: 15_suppl
  year: 2018
  article-title: Phase I/II study of the A R antagonist NIR178 (PBF‐509), an oral immunotherapy, in patients (pts) with advanced NSCLC
  publication-title: Journal of Clinical Oncology
– volume: 55
  start-page: 1904
  issue: 5
  year: 2012
  end-page: 1909
  article-title: Identification of novel adenosine A receptor antagonists by virtual screening
  publication-title: Journal of Medicinal Chemistry
– volume: 100
  start-page: 931
  issue: 4
  year: 2011
  end-page: 938
  article-title: Single ryanodine receptor channel basis of caffeine's action on Ca sparks
  publication-title: Biophysical Journal
– volume: 54
  start-page: 308
  issue: 4
  year: 2016
  end-page: 312
  article-title: Pharmacokinetic analysis and comparison of caffeine administered rapidly or slowly in coffee chilled or hot versus chilled energy drink in healthy young adults
  publication-title: Clinical Toxicology (Philadelphia, Pa.)
– volume: 172
  start-page: 68
  year: 2018
  end-page: 80
  article-title: Allosteric coupling of drug binding and intracellular signaling in the A adenosine receptor
  publication-title: Cell
– volume: 23
  start-page: 669
  issue: 8
  year: 2019
  end-page: 678
  article-title: Targeting A and A adenosine receptors in the fight against cancer
  publication-title: Expert Opinion on Therapeutic Targets
– volume: 13
  start-page: 124
  year: 2019
  article-title: Historical and current adenosine receptor agonists in preclinical and clinical development
  publication-title: Frontiers in Cellular Neuroscience
– volume: 253
  start-page: 359
  year: 2019
  end-page: 381
  article-title: Adenosine and sleep
  publication-title: Handbook of Experimental Pharmacology
– volume: 388
  start-page: 674
  issue: 6643
  year: 1997
  end-page: 678
  article-title: Aggressiveness, hypoalgesia and high blood pressure in mice lacking the adenosine receptor
  publication-title: Nature
– volume: 52
  start-page: 3284
  issue: 10
  year: 2009
  end-page: 3292
  article-title: Evaluation of Homology Modeling of G‐Protein‐Coupled Receptors in Light of the A2AAdenosine Receptor Crystallographic Structure
  publication-title: Journal of Medicinal Chemistry
– volume: 318
  start-page: 1258
  issue: 5854
  year: 2007
  end-page: 1265
  article-title: High‐resolution crystal structure of an engineered human beta2‐adrenergic G protein‐coupled receptor
  publication-title: Science
– volume: 9
  start-page: 79
  year: 2018
  article-title: Long‐term treatment with low‐dose caffeine worsens BPSD‐like profile in 3xTg‐AD mice model of Alzheimer's disease and affects mice with normal aging
  publication-title: Frontiers in Pharmacology
– volume: 176
  start-page: S297
  year: 2019
  end-page: S396
  article-title: THE CONCISE GUIDE TO PHARMACOLOGY 2019/20: Enzymes
  publication-title: British Journal of Pharmacology
– volume: 10
  start-page: 611
  year: 2018
  article-title: Caffeine‐related deaths: Manner of deaths and categories at risk
  publication-title: Nutrients
– volume: 8
  start-page: 131
  issue: 4
  year: 2018
  end-page: 142
  article-title: Promises of caffeine in attention‐deficit/hyperactivity disorder: From animal models to clinical practice
  publication-title: Journal of Caffeine and Adenosine Research
– volume: 4
  start-page: 425
  issue: 4
  year: 2018
  end-page: 432
  article-title: Caffeine and arrhythmias
  publication-title: JACC: Clin Electrophysiol
– volume: 9
  start-page: 13593
  issue: 17
  year: 2018
  end-page: 13611
  article-title: Adenosine A receptor ligand recognition and signaling is blocked by A receptors
  publication-title: Oncotarget
– volume: 99
  start-page: 8921
  issue: 13
  year: 2002
  end-page: 8926
  article-title: A molecular mechanism of action of theophylline: Induction of histone deacetylase activity to decrease inflammatory gene expression
  publication-title: Proceedings of the National Academy of Sciences of the United States of America
– volume: 337
  start-page: 232
  year: 2012
  end-page: 236
  article-title: Structural basis for allosteric regulation of GPCRs by sodium ions
  publication-title: Science (New York, N.Y.)
– volume: 19
  start-page: 41
  year: 2018
  article-title: Characterization of the trigeminovascular actions of several adenosine A receptor antagonists in an in vivo rat model of migraine
  publication-title: The Journal of Headache and Pain
– volume: 474
  start-page: 521
  year: 2011
  end-page: 525
  article-title: Agonist‐bound adenosine A receptor structures reveal common features of GPCR activation
  publication-title: Nature
– volume: 244
  start-page: 569
  issue: 4904
  year: 1989
  end-page: 572
  article-title: Selective amplification and cloning of four new members of the G protein‐coupled receptor family
  publication-title: Science
– volume: 27
  start-page: 703
  issue: 4
  year: 2019
  end-page: 712
  article-title: Dynamic role of the G protein in stabilizing the active state of the adenosine A receptor
  publication-title: Structure
– volume: 16
  start-page: 1609
  issue: 12
  year: 1969
  end-page: 1619
  article-title: A radioisotopic method for measuring the formation of adenosine 3′,5′‐cyclic monophosphate in incubated slices of brain
  publication-title: Journal of Neurochemistry
– volume: 78
  start-page: 1003
  issue: 4
  year: 2018
  end-page: 1016
  article-title: A R adenosine signaling suppresses natural killer cell maturation in the tumor microenvironment
  publication-title: Cancer Research
– volume: 2017
  start-page: 12
  year: 2017
  end-page: 12
  article-title: Having a coffee break: The impact of caffeine consumption on microglia‐mediated inflammation in neurodegenerative diseases
  publication-title: Mediators of Inflammation
– volume: 46
  start-page: D1091
  year: 2018
  end-page: D1106
  article-title: The IUPHAR/BPS guide to pharmacology in 2018: Updates and expansion to encompass the new guide to immunopharmacology
  publication-title: Nucleic Acids Research
– volume: 61
  start-page: 761
  issue: 9
  year: 2006
  end-page: 766
  article-title: Inhibition of reactive nitrogen species production in COPD airways: Comparison of inhaled corticosteroid and oral theophylline
  publication-title: Thorax
– volume: 23
  start-page: 174
  year: 2017
  end-page: 184
  article-title: Expression of specific inflammasome gene modules stratifies older individuals into two extreme clinical and immunological states
  publication-title: Nature Medicine
– volume: 37
  start-page: 711
  year: 2019
  end-page: 721
  article-title: Safety, tolerability, and pharmacology of AB928, a novel dual adenosine receptor antagonist, in a randomized, phase 1 study in healthy volunteers
  publication-title: Investigational New Drugs
– volume: 117
  start-page: 21
  issue: 1
  year: 2017
  end-page: 37
  article-title: Structurally enabled discovery of adenosine A receptor antagonists
  publication-title: Chemical Reviews
– volume: 17
  issue: 3
  year: 2019
  article-title: Physiology and effects of nucleosides in mice lacking all four adenosine receptors
  publication-title: PLoS Biology
– volume: 10
  start-page: 160
  issue: 3
  year: 2020
  article-title: Purinergic signaling and related biomarkers in depression
  publication-title: Brain Sciences
– volume: 19
  start-page: 1635
  issue: 15
  year: 2018
  end-page: 1642
  article-title: Safety and effectiveness of istradefylline in patients with Parkinson's disease: Interim analysis of a post‐marketing surveillance study in Japan
  publication-title: Expert Opinion on Pharmacotherapy
– volume: 169
  start-page: 1372
  issue: 6
  year: 2013
  end-page: 1388
  article-title: Activation of adenosine A receptor reduces osteoclast formation via PKA‐ and ERK1/2‐mediated suppression of NFκB nuclear translocation
  publication-title: British Journal of Pharmacology
– volume: 59
  start-page: 10,564
  year: 2016
  end-page: 10,576
  article-title: Design, synthesis, and pharmacological characterization of 2‐(2‐furanyl)thiazolo[5,4‐d]pyrimidine‐5,7‐diamine derivatives: New highly potent A adenosine receptor inverse agonists with antinociceptive activity
  publication-title: Journal of Medicinal Chemistry
– volume: 9
  start-page: 73
  issue: 3
  year: 2019
  end-page: 88
  article-title: Neurogenetics of the human adenosine receptor genes: Genetic structures and involvement in brain diseases
  publication-title: Journal of Caffeine and Adenosine Research
– volume: 13
  start-page: 247
  year: 1993
  end-page: 261
  article-title: Chronic caffeine alters the density of adenosine, adrenergic, cholinergic, GABA, and serotonin receptors and calcium channels in mouse brain
  publication-title: Cellular and Molecular Neurobiology
– volume: 96
  start-page: 665
  issue: 3
  year: 2012
  end-page: 671
  article-title: Associations between polymorphisms in the AHR and CYP1A1‐CYP1A2 gene regions and habitual caffeine consumption
  publication-title: American Journal of Clinical Nutrition
– volume: 117
  start-page: 72
  year: 2018
  end-page: 81
  article-title: Blockade of adenosine A receptors recovers early deficits of memory and plasticity in the triple transgenic mouse model of Alzheimer's disease
  publication-title: Neurobiology of Disease
– volume: 54
  start-page: 4312
  issue: 13
  year: 2011
  end-page: 4323
  article-title: Biophysical mapping of the adenosine A receptor
  publication-title: Journal of Medicinal Chemistry
– volume: 18
  start-page: 423
  year: 2015
  end-page: 434
  article-title: Astrocytic adenosine receptor A and G ‐coupled signaling regulate memory
  publication-title: Nature Neuroscience
– volume: 232
  start-page: 1077
  issue: 2
  year: 1958
  end-page: 1091
  article-title: Fractionation and characterization of a cyclic adenine ribonucleotide formed by tissue particles
  publication-title: The Journal of Biological Chemistry
– volume: 86
  start-page: 6572
  year: 1989
  end-page: 6576
  article-title: Identification of the A adenosine receptor binding subunit by photoaffinity crosslinking
  publication-title: Proceedings of the National Academy of Sciences of the United States of America
– volume: 45
  start-page: 847
  issue: 4
  year: 1993
  end-page: 851
  article-title: Adenosine receptor‐blocking xanthines as inhibitors of phosphodiesterase isozymes
  publication-title: Biochemical Pharmacology
– volume: 142
  start-page: 3636
  year: 2019
  end-page: 3654
  article-title: Exacerbation of C1q dysregulation, synaptic loss and memory deficits in tau pathology linked to neuronal adenosine A receptors
  publication-title: Brain
– volume: 8
  start-page: 8142
  year: 2018
  article-title: Enabling STD‐NMR fragment screening using stabilized native GPCR: A case study of adenosine receptor
  publication-title: Scientific Reports
– year: 2018
  article-title: Age‐related shift in LTD is dependent on neuronal adenosine A receptors interplay with mGluR5 and NMDA receptors
  publication-title: Molecular Psychiatry
– volume: 558
  start-page: 559
  issue: 7711
  year: 2018
  end-page: 563
  article-title: Structure of the adenosine‐bound human adenosine A1 receptor–Gi complex
  publication-title: Nature
– volume: 8
  start-page: 898
  year: 2017
  article-title: Human adenosine A receptor: Molecular mechanism of ligand binding and activation
  publication-title: Frontiers in Pharmacology
– volume: 67
  start-page: 476
  year: 2013
  end-page: 484
  article-title: Psychostimulant pharmacological profile of paraxanthine, the main metabolite of caffeine in humans
  publication-title: Neuropharmacology
– volume: 294
  start-page: 13,218
  issue: 36
  year: 2019
  end-page: 13,223
  article-title: Detergent‐and phospholipid‐based reconstitution systems have differential effects on constitutive activity of G‐protein–coupled receptors
  publication-title: The Journal of Biological Chemistry
– volume: 59
  start-page: 6470
  issue: 13
  year: 2016
  end-page: 6479
  article-title: Controlling the dissociation of ligands from the adenosine A receptor through modulation of salt bridge strength
  publication-title: Journal of Medicinal Chemistry
– volume: 12
  start-page: 520
  year: 2018
  article-title: The adenosinergic signaling: A complex but promising therapeutic target for Alzheimer's disease
  publication-title: Frontiers in Neuroscience
– volume: 64
  start-page: 3344
  issue: 9
  year: 2004
  end-page: 3349
  article-title: Caffeine inhibits cell proliferation by G /G phase arrest in JB6 cells
  publication-title: Cancer Research
– volume: 51
  start-page: 83
  issue: 1
  year: 1999
  end-page: 133
  article-title: Actions of caffeine in the brain with special reference to factors that contribute to its widespread use
  publication-title: Pharmacological Reviews
– volume: 21
  start-page: 974
  issue: 8
  year: 2016
  article-title: Structure‐bioactivity relationships of methylxanthines: Trying to make sense of all the promises and the drawbacks
  publication-title: Molecules
– volume: 318
  start-page: 1266
  issue: 5854
  year: 2007
  end-page: 1273
  article-title: GPCR engineering yields high‐resolution structural insights into beta ‐adrenergic receptor function
  publication-title: Science
– volume: 68
  start-page: 213
  year: 1929
  end-page: 237
  article-title: The physiological activity of adenine compounds with especial reference to their action upon the mammalian heart
  publication-title: The Journal of Physiology
– volume: 99
  start-page: 1129
  issue: 6
  year: 2018
  end-page: 1143
  article-title: Molecular dynamics simulation for all
  publication-title: Neuron
– volume: 1
  start-page: 293
  issue: 2
  year: 2016
  end-page: 304
  article-title: Predicting binding affinities for GPCR ligands using free‐energy perturbation
  publication-title: ACS Omega
– volume: 10
  start-page: 40
  issue: 1
  year: 2020
  end-page: 53
  article-title: Adenosine 2A receptor blockade as an immunotherapy for treatment‐refractory renal cell cancer
  publication-title: Cancer Discovery
– volume: 332
  start-page: 322
  year: 2011
  end-page: 327
  article-title: Structure of an agonist‐bound human A adenosine receptor
  publication-title: Science
– volume: 9
  start-page: 1372
  year: 2018
  article-title: Mechanistic insights into allosteric regulation of the A adenosine G protein‐coupled receptor by physiological cations
  publication-title: Nature Communications
– volume: 176
  start-page: S21
  issue: Suppl 1
  year: 2019
  end-page: S141
  article-title: THE CONCISE GUIDE TO PHARMACOLOGY 2019/20: G protein‐coupled receptors
  publication-title: British Journal of Pharmacology
– volume: 5
  start-page: 37
  year: 2019
  article-title: Caffeine consumption through coffee: Content in the beverage, metabolism, health benefits and risks
  publication-title: Beverages
– volume: 201
  start-page: 782
  issue: 2
  year: 2018
  end-page: 791
  article-title: A adenosine receptor gene deletion or synthetic A antagonist liberate tumor‐reactive CD8 T cells from tumor‐induced immunosuppression
  publication-title: The Journal of Immunology
– volume: 8
  start-page: 80
  year: 2017
  article-title: The safety of ingested caffeine: A comprehensive review
  publication-title: Frontiers in Psychiatry
– volume: 12
  start-page: 211
  year: 1982
  end-page: 215
  article-title: The clinical and pharmacological history of theophylline: First report on the bronchospasmolytic action in man by S. R. Hirsch in Frankfurt (Main) 1922
  publication-title: Clinical Allergy
– year: 2020
  article-title: The belated US FDA approval of the adenosine A receptor antagonist istradefylline for treatment of Parkinson's disease
  publication-title: Purinergic Signal
– start-page: 1
  year: 2019
  end-page: 19
– volume: 16
  start-page: 327
  issue: 5
  year: 1920
  end-page: 344
  article-title: The action of caffeine, theobromine and theophylline on the mammalian and batrachian heart
  publication-title: The Journal of Pharmacology and Experimental Therapeutics
– volume: 132
  start-page: 104570
  year: 2019
  article-title: Synaptic and memory dysfunction in a β‐amyloid model of early Alzheimer's disease depends on increased formation of ATP‐derived extracellular adenosine
  publication-title: Neurobiology of Disease
– volume: 61
  start-page: 5269
  issue: 12
  year: 2018
  end-page: 5278
  article-title: Docking screens for dual inhibitors of disparate drug targets for Parkinson's disease
  publication-title: Journal of Medicinal Chemistry
– volume: 104
  start-page: 31
  year: 2016
  end-page: 49
  article-title: Medicinal chemistry of adenosine, P2Y and P2X receptors
  publication-title: Neuropharmacology
– volume: 176
  start-page: S1
  year: 2019
  end-page: S20
  article-title: THE CONCISE GUIDE TO PHARMACOLOGY 2019/20: Other Protein Targets
  publication-title: British Journal of Pharmacology
– volume: 366
  start-page: 1891
  year: 2012
  end-page: 1904
  article-title: Association of coffee drinking with total and cause‐specific mortality
  publication-title: New Engl J Med
– volume: 289
  start-page: 739
  year: 2000
  end-page: 745
  article-title: Crystal structure of rhodopsin: A G protein‐coupled receptor
  publication-title: Science
– volume: 72
  start-page: 214
  issue: 2
  year: 2018
  end-page: 222
  article-title: Coffee consumption and incident kidney disease: Results from the atherosclerosis risk in communities (ARIC) study
  publication-title: American Journal of Kidney Diseases
– volume: 533
  start-page: 265
  year: 2016
  end-page: 268
  article-title: Activation of the A adenosine G‐protein‐coupled receptor by conformational selection
  publication-title: Nature
– volume: 78
  start-page: 3260
  issue: 5
  year: 1981
  end-page: 3264
  article-title: Adenosine receptors and behavioral actions of methylxanthines
  publication-title: Proceedings of the National Academy of Sciences of the United States of America
– volume: 40
  start-page: 79
  year: 2015
  end-page: 87
  article-title: The importance of ligands for G protein‐coupled receptor stability
  publication-title: Trends in Biochemical Sciences
– volume: 8
  start-page: 947
  year: 2017
  article-title: Purinergic signaling in mast cell degranulation and asthma
  publication-title: Frontiers in Pharmacology
– volume: 7
  start-page: 11915
  issue: 1
  year: 2016
  article-title: Early synaptic deficits in the APP/PS1 mouse model of Alzheimer’s disease involve neuronal adenosine A2A receptors
  publication-title: Nature Communications
– volume: 148
  start-page: 202
  issue: 2
  year: 1965
  end-page: 214
  article-title: Effects of caffeine on mammalian atrial muscle, and its interaction with adenosine and calcium
  publication-title: The Journal of Pharmacology and Experimental Therapeutics
– volume: 77
  start-page: 2551
  issue: 5
  year: 1980
  end-page: 2554
  article-title: Subclasses of external adenosine receptors
  publication-title: Proceedings of the National Academy of Sciences of the United States of America
– volume: 112
  start-page: 7833
  year: 2015
  end-page: 7838
  article-title: Caffeine acts through neuronal adenosine A receptors to prevent mood and memory dysfunction triggered by chronic stress
  publication-title: Proceedings of the National Academy of Sciences of the United States of America
– volume: 18
  start-page: 1
  issue: 1
  year: 2018
  end-page: 3
  article-title: Coffee consumption and prevention of cirrhosis: In support of the caffeine hypothesis
  publication-title: Gene Expression
– volume: 114
  start-page: 2066
  issue: 8
  year: 2017
  end-page: 2071
  article-title: Crystal structure of the adenosine A2A receptor bound to an antagonist reveals a potential allosteric pocket
  publication-title: Proceedings of the National Academy of Sciences
– volume: 33
  start-page: 55
  year: 2010
  end-page: 60
  article-title: An open‐label, positron emission tomography study to assess adenosine A brain receptor occupancy of Vipadenant (BIIB014) at steady‐state levels in healthy male volunteers
  publication-title: Clinical Neuropharmacology
– volume: 139
  start-page: 1019
  year: 2016
  end-page: 1055
  article-title: How does adenosine control neuronal dysfunction and neurodegeneration?
  publication-title: Journal of Neurochemistry
– volume: 8
  start-page: 41
  year: 2018
  article-title: Towards high throughput GPCR crystallography: In Meso soaking of adenosine A receptor crystals
  publication-title: Scientific Reports
– volume: 63
  start-page: 613
  issue: 2
  year: 2020
  end-page: 620
  article-title: Docking finds GPCR ligands in dark chemical matter
  publication-title: Journal of Medicinal Chemistry
– volume: 5
  year: 2013
  article-title: Adenosine receptor antagonists including caffeine alter fetal brain development in mice
  publication-title: Science Translational Medicine
– volume: 26
  start-page: 259
  year: 2018
  end-page: 269
  article-title: Structural connection between activation microswitch and allosteric sodium site in GPCR signaling
  publication-title: Structure
– volume: 11
  start-page: 1936
  issue: 17
  year: 2016
  end-page: 1943
  article-title: Synthesis and in vivo evaluation of fluorine‐18 and iodine‐123 pyrazolo[4,3‐e]‐1,2,4‐triazolo[1,5‐c]pyrimidine derivatives as PET and SPECT radiotracers for mapping A receptors
  publication-title: ChemMedChem
– volume: 43
  start-page: 439
  issue: 2
  year: 2018
  end-page: 448
  article-title: Stimulation of intestinal Cl‐ secretion through CFTR by caffeine intake in salt‐sensitive hypertensive rats
  publication-title: Kidney & Blood Pressure Research
– volume: 231
  start-page: 586
  issue: 6
  year: 1957
  end-page: 590
  article-title: Antagonism between adenosine & methylxanthine at the bundle of His of the heart
  publication-title: Naunyn‐Schmiedebergs Archiv für Experimentelle Pathologie Und Pharmakologie
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Snippet A long evolution of knowledge of the psychostimulant caffeine led in the 1960s to another purine natural product, adenosine and its A2A receptor. Adenosine is...
A long evolution of knowledge of the psychostimulant caffeine led in the 1960s to another purine natural product, adenosine and its A 2A receptor. Adenosine is...
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SubjectTerms Adenosine
Adenosine A2A receptors
Aging
Autocrine signalling
Caffeine
Clinical trials
Diabetes mellitus
Drug development
Immunotherapy
Liver diseases
Membrane proteins
Natural products
Neurodegenerative diseases
Paracrine signalling
Xanthines
Title Adenosine A2A receptor antagonists: from caffeine to selective non‐xanthines
URI https://onlinelibrary.wiley.com/doi/abs/10.1111%2Fbph.15103
https://www.proquest.com/docview/2676583301
https://www.proquest.com/docview/2404643724
https://pubmed.ncbi.nlm.nih.gov/PMC9251831
Volume 179
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