Editing Adenosine receptor

{{Short description|Class of four receptor proteins to the molecule adenosine}}
{{Purinergic signalling}}

The '''adenosine receptors''' (or '''P1 receptors'''<ref name="pmid9133776">{{cite journal | vauthors = Fredholm BB, Abbracchio MP, Burnstock G, Dubyak GR, Harden TK, Jacobson KA, Schwabe U, Williams M | title = Towards a revised nomenclature for P1 and P2 receptors | journal = Trends Pharmacol. Sci. | volume = 18 | issue = 3 | pages = 79–82 | year = 1997 | pmid = 9133776 | doi = 10.1016/S0165-6147(96)01038-3 | pmc = 4460977 }}</ref>) are a class of [[Purinergic receptor|purinergic]] [[G protein-coupled receptor]]s with [[adenosine]] as the [[endogenous]] [[ligand (biochemistry)|ligand]].<ref name="pmid11734617">{{cite journal | vauthors = Fredholm BB, IJzerman AP, Jacobson KA, Klotz KN, Linden J | title = International Union of Pharmacology. XXV. Nomenclature and classification of adenosine receptors | journal = Pharmacol. Rev. | volume = 53 | issue = 4 | pages = 527–52 | year = 2001 | pmid = 11734617 | url = http://pharmrev.aspetjournals.org/cgi/content/abstract/53/4/527 }}</ref> There are four known types of adenosine receptors in humans: [[Adenosine A1 receptor|A<sub>1</sub>]], [[Adenosine A2A receptor|A<sub>2A</sub>]], [[Adenosine A2B receptor|A<sub>2B</sub>]] and [[Adenosine A3 receptor|A<sub>3</sub>]]; each is encoded by a different [[gene]].

The adenosine receptors are commonly known for their antagonists [[caffeine]], [[theophylline]], and [[theobromine]], whose action on the receptors produces the stimulating effects of [[coffee]], [[tea]] and [[chocolate]].

==Pharmacology==
[[File:10 caffeine knowing-neurons.jpg|thumb|Caffeine keeps you awake by blocking adenosine receptors.]]

Each type of adenosine receptor has different functions, although with some overlap.<ref name="pmid17874974">{{cite journal | vauthors = Gao ZG, Jacobson KA | title = Emerging adenosine receptor agonists | journal = Expert Opinion on Emerging Drugs | volume = 12 | issue = 3 | pages = 479–92 |date=September 2007| pmid = 17874974 | doi = 10.1517/14728214.12.3.479 | url =  https://zenodo.org/record/1236313| pmc = 11790296 }}</ref> For instance, both A<sub>1</sub> receptors and A<sub>2A</sub> play roles in the heart, regulating [[myocardial]] oxygen consumption and [[Coronary circulation|coronary]] blood flow, while the A<sub>2A</sub> receptor also has broader anti-inflammatory effects throughout the body.<ref name="pmid18160539">{{cite journal | vauthors = Haskó G, Pacher P | title = A2A receptors in inflammation and injury: lessons learned from transgenic animals | journal = Journal of Leukocyte Biology | volume = 83 | issue = 3 | pages = 447–55 |date=March 2008| pmid = 18160539 | pmc = 2268631 | doi = 10.1189/jlb.0607359 }}</ref> These two receptors also have important roles in the brain,<ref name="pmid16806272">{{cite journal | vauthors = Kalda A, Yu L, Oztas E, Chen JF | title = Novel neuroprotection by caffeine and adenosine A(2A) receptor antagonists in animal models of Parkinson's disease | journal = Journal of the Neurological Sciences | volume = 248 | issue = 1–2 | pages = 9–15 |date=October 2006| pmid = 16806272 | doi = 10.1016/j.jns.2006.05.003 }}</ref> regulating the release of other [[neurotransmitter]]s such as [[dopamine]] and [[glutamate]],<ref name="pmid17572452">{{cite journal | vauthors = Fuxe K, Ferré S, Genedani S, Franco R, Agnati LF | title = Adenosine receptor-dopamine receptor interactions in the basal ganglia and their relevance for brain function | journal = Physiology & Behavior | volume = 92 | issue = 1–2 | pages = 210–7 |date=September 2007| pmid = 17572452 | doi = 10.1016/j.physbeh.2007.05.034 }}</ref><ref name="pmid17646043">{{cite journal | vauthors = Schiffmann SN, Fisone G, Moresco R, Cunha RA, Ferré S | title = Adenosine A2A receptors and basal ganglia physiology | journal = Progress in Neurobiology | volume = 83 | issue = 5 | pages = 277–92 |date=December 2007| pmid = 17646043 | pmc = 2148496 | doi = 10.1016/j.pneurobio.2007.05.001 }}</ref><ref name="pmid18537674">{{cite journal | vauthors = Cunha RA, Ferré S, Vaugeois JM, Chen JF | title = Potential therapeutic interest of adenosine A2A receptors in psychiatric disorders | journal = Current Pharmaceutical Design | volume = 14 | issue = 15 | pages = 1512–24 | year = 2008 | pmid = 18537674 | pmc = 2423946 | doi = 10.2174/138161208784480090}}</ref> while the A<sub>2B</sub> and A<sub>3</sub> receptors are located mainly peripherally and are involved in processes such as inflammation and immune responses.

Most older compounds acting on adenosine receptors are nonselective, with the endogenous agonist [[adenosine]] being used in hospitals as treatment for severe [[tachycardia]] (rapid heart beat),<ref name="pmid17408751">{{cite journal | vauthors = Peart JN, Headrick JP | title = Adenosinergic cardioprotection: multiple receptors, multiple pathways | journal = Pharmacology & Therapeutics | volume = 114 | issue = 2 | pages = 208–21 |date=May 2007| pmid = 17408751 | doi = 10.1016/j.pharmthera.2007.02.004 }}</ref> and acting directly to slow the heart through action on all four adenosine receptors in heart tissue,<ref name="pmid17999026">{{cite journal | vauthors = Cohen MV, Downey JM | title = Adenosine: trigger and mediator of cardioprotection | journal = Basic Research in Cardiology | volume = 103 | issue = 3 | pages = 203–15 |date=May 2008| pmid = 17999026 | doi = 10.1007/s00395-007-0687-7 }}</ref> as well as producing a [[sedative]] effect through action on A<sub>1</sub> and A<sub>2A</sub> receptors in the brain. [[Xanthine]] derivatives such as [[caffeine]] and [[theophylline]] act as non-selective [[antagonist (pharmacology)|antagonists]] at A<sub>1</sub> and A<sub>2A</sub> receptors in both heart and brain and so have the opposite effect to adenosine, producing a [[stimulant]] effect and rapid heart rate.<ref name="pmid18088379">{{cite journal | author = Ferré S | title = An update on the mechanisms of the psychostimulant effects of caffeine | journal = Journal of Neurochemistry | volume = 105 | issue = 4 | pages = 1067–79 |date=May 2008| pmid = 18088379 | doi = 10.1111/j.1471-4159.2007.05196.x | doi-access = free }}</ref> These compounds also act as [[phosphodiesterase inhibitor]]s, which produces additional [[anti-inflammatory]] effects, and makes them medically useful for the treatment of conditions such as [[asthma]], but less suitable for use in scientific research.<ref name="pmid17373584">{{cite journal | author = Osadchii OE | title = Myocardial phosphodiesterases and regulation of cardiac contractility in health and cardiac disease | journal = Cardiovascular Drugs and Therapy | volume = 21 | issue = 3 | pages = 171–94 |date=June 2007| pmid = 17373584 | doi = 10.1007/s10557-007-6014-6 }}</ref>

Newer adenosine receptor agonists and antagonists are much more potent and subtype-selective, and have allowed extensive research into the effects of blocking or stimulating the individual adenosine receptor subtypes, which is now resulting in a new generation of more selective drugs with many potential medical uses. Some of these compounds are still derived from adenosine or from the xanthine family, but researchers in this area have also discovered many selective adenosine receptor ligands that are entirely structurally distinct, giving a wide range of possible directions for future research.<ref name="pmid18181659">{{cite journal | vauthors = Baraldi PG, Tabrizi MA, Gessi S, Borea PA | title = Adenosine receptor antagonists: translating medicinal chemistry and pharmacology into clinical utility | journal = Chemical Reviews | volume = 108 | issue = 1 | pages = 238–63 |date=January 2008| pmid = 18181659 | doi = 10.1021/cr0682195 }}</ref><ref name="pmid18537675">{{cite journal | vauthors = Cristalli G, Lambertucci C, Marucci G, Volpini R, Dal Ben D | title = A2A adenosine receptor and its modulators: overview on a druggable GPCR and on structure-activity relationship analysis and binding requirements of agonists and antagonists | journal = Current Pharmaceutical Design | volume = 14 | issue = 15 | pages = 1525–52 | year = 2008 | pmid = 18537675 | doi = 10.2174/138161208784480081}}</ref>

==Subtypes==
===Comparison===
{| class="wikitable"
|+Adenosine receptors
|-
! Receptor !! Gene !! Mechanism <ref>Unless else specified in boxes, then ref is:[http://senselab.med.yale.edu/NeuronDB/receptors2.asp#Neuropeptide%20Y%20receptors, senselab] {{Webarchive|url=https://web.archive.org/web/20090228070451/http://senselab.med.yale.edu/NeuronDB/receptors2.asp#Neuropeptide%20Y%20receptors, |date=2009-02-28 }}</ref> !! Effects !! Agonists !! Antagonists
|-
! '''[[Adenosine A1 receptor|A<sub>1</sub>]]'''
| {{Gene|ADORA1}} || [[Gi alpha subunit|G<sub>i/o</sub>]] → [[Cyclic adenosine monophosphate|cAMP]]↑/↓
* Inhibition
**↓ vesicle release
* [[Bronchoconstriction]]
* Afferent arteriolar constriction in Kidney

||
* Decreased [[heart rate]]
|| 
*[[N6-Cyclopentyladenosine]]
*N6-3-methoxyl-4-hydroxybenzyl adenine riboside (B2)
*[[Adenosine]]
*[[CCPA (biochemistry)|CCPA]]
*Certain [[Benzodiazepine]]s and [[Barbiturate]]s
*2'-MeCCPA
*GR 79236
*SDZ WAG 994
*Benzyloxy-cyclopentyladenosine (BnOCPA)
|| 
*[[Caffeine]]
*[[Theophylline]]
*[[8-Cyclopentyl-1,3-dimethylxanthine]] (CPX)
*[[8-Cyclopentyl-1,3-dipropylxanthine]] (DPCPX)
*[[8-Phenyl-1,3-dipropylxanthine]]
*PSB 36
|-
! '''[[Adenosine A2A receptor|A<sub>2A</sub>]]'''
| {{Gene|ADORA2A}} || [[Gs alpha subunit|G<sub>s</sub>]] → [[Cyclic adenosine monophosphate|cAMP]]↑ || 
* [[coronary circulation|Coronary artery]] [[vasodilatation]]
* Decreased dopaminergic activity in CNS
* Inhibition of central neuron excitation.
|| 
*N6-3-methoxyl-4-hydroxybenzyl adenine riboside (B2)
*ATL-146e
*[[CGS-21680]]
*[[Regadenoson]]
*[[Adenosine]]
 || 
*[[Caffeine]]
*[[Aminophylline]]
*[[Theophylline]]
*[[Istradefylline]]
*[[SCH-58261]]
*[[SCH-442,416]]
*[[ZM-241,385]]
|-
! '''[[Adenosine A2B receptor|A<sub>2B</sub>]]'''
| {{Gene|ADORA2B}} || [[Gs alpha subunit|G<sub>s</sub>]] → [[Cyclic adenosine monophosphate|cAMP]]↑

Also recently discovered A<sub>2B</sub> has Gq → [[Diglyceride|DAG]] and [[Inositol triphosphate|IP3]] → Release calcium → activate calmodulin → activate [[myosin light chain kinase]] → phosphorylate myosin light chain → myosin light chain plus actin → bronchoconstriction{{Citation needed|date=November 2011}}
|| 
*[[Bronchospasm]]
|| 
*5'-N-ethylcarboxamidoadenosine
*[[BAY 60–6583]]
*[[Adenosine]]
*LUF-5835
*LUF-5845
||
*[[Theophylline]]
*[[Caffeine]]
*[[CVT-6883]]
*[[MRS-1706]]
*MRS-1754
*PSB-603
*PSB-0788
*PSB-1115
|-
! '''[[Adenosine A3 receptor|A<sub>3</sub>]]'''
| {{Gene|ADORA3}} || [[Gi alpha subunit|G<sub>i/o</sub>]] → ↓cAMP|| 
*Cardiac muscle relaxation
*Smooth muscle contraction
*Cardioprotective in [[cardiac ischemia]]
*Inhibition of neutrophil [[degranulation]]
|| 
*2-(1-Hexynyl)-N-methyladenosine
*CF-101 (IB-MECA)
*[[Adenosine]]
*2-Cl-IB-MECA
*[[CP-532,903]]
*MRS-3558
 ||
*[[Theophylline]]
*[[Caffeine]]
*MRS-1191
*MRS-1220
*MRS-1334
*MRS-1523
*MRS-3777
*MRE3008F20
*PSB-10
*PSB-11
*VUF-5574
|-
|}

===A<sub>1</sub> adenosine receptor===
{{Main|Adenosine A1 receptor}}
The adenosine A<sub>1</sub> receptor has been found to be ubiquitous throughout the entire body.

====Mechanism====
This receptor has an inhibitory function on most of the tissues in which it is expressed. In the brain, it slows metabolic activity by a combination of actions. Presynaptically, it reduces [[synaptic vesicle]] release while post synaptically it has been found to stabilize the [[Magnesium in biology|magnesium]] on the [[NMDA receptor]]<sup>source?</sup>.

====Antagonism and agonism====
{{See also|Adenosine receptor agonist|Adenosine receptor antagonist|Adenosine reuptake inhibitor}}
Specific A<sub>1</sub> [[receptor antagonist|antagonists]] include [[8-Cyclopentyl-1,3-dipropylxanthine|8-cyclopentyl-1,3-dipropyl xanthine]] (DPCPX), and [[8-Cyclopentyl-1,3-dimethylxanthine|cyclopentyltheophylline]] (CPT) or 8-cyclopentyl-1,3-[[dipropylxanthine]] (CPX), while specific agonists include 2-chloro-N(6)-cyclopentyladenosine ([[CCPA (biochemistry)|CCPA]]).

[[Tecadenoson]] is an effective A<sub>1</sub> adenosine agonist, as is [[selodenoson]].

====In the heart====
The A<sub>1</sub>, together with A<sub>2A</sub> receptors of endogenous adenosine play a role in regulating [[myocardial]] oxygen consumption and coronary blood flow. Stimulation of the A<sub>1</sub> receptor has a myocardial depressant effect by decreasing the conduction of electrical impulses and suppressing [[Cardiac pacemaker|pacemaker]] cell function, resulting in a decrease in [[heart rate]]. This makes adenosine a useful medication for treating and diagnosing ''[[tachyarrhythmia]]s'', or excessively fast heart rates. This effect on the A<sub>1</sub> receptor also explains why there is a brief moment of cardiac standstill when adenosine is administered as a rapid [[intravenous|IV]] push during [[cardiac resuscitation]]. The rapid infusion causes a momentary myocardial stunning effect.

In normal physiological states, this serves as a protective mechanism. However, in altered cardiac function, such as [[hypoperfusion]] caused by [[hypotension]], [[heart attack]] or [[cardiac arrest]] caused by [[nonperfusing bradycardia]]s (e.g., [[ventricular fibrillation]] or [[pulseless ventricular tachycardia]]<ref name="Ong2016">{{cite book |last1=Ong |first1=MH |last2=Lim |first2=S |last3=Venkataraman |first3=A |title=Tintinalli’s Emergency Medicine: A Comprehensive Study Guide, 8e |date=2016 |publisher=McGraw-Hill Education |isbn=978-0071794763 |chapter-url=https://accessmedicine.mhmedical.com/content.aspx?bookid=1658&sectionid=109427163 |chapter=23: Defibrillation and Cardioversion |access-date=30 March 2024}}</ref>), adenosine has a negative effect on physiological functioning by preventing necessary compensatory increases in heart rate and blood pressure that attempt to maintain cerebral perfusion.

====In neonatal medicine====
Adenosine antagonists are widely used in [[neonatal medicine]];

A reduction in A<sub>1</sub> expression appears to prevent hypoxia-induced [[ventriculomegaly]] and loss of white matter, which raises the possibility that pharmacological blockade of A<sub>1</sub> may have clinical utility.

Theophylline and caffeine are nonselective adenosine antagonists that are used to stimulate respiration in premature infants.

====Bone homeostasis====
Adenosine receptors play a key role in the homeostasis of bone. The A<sub>1</sub> receptor has been shown to stimulate [[osteoclast]] differentiation and function.<ref>Kara FM, Doty SB, Boskey A, Goldring S.. (2010). Adenosine A1 Receptors (A1R) Regulate Bone Resorption II Adenosine A1R Blockade or Deletion Increases Bone Density and Prevents Ovariectomy-Induced Bone Loss. Arthritis Rheumatology . 62 (2), 534–541.</ref> Studies have found that blockade of the A<sub>1</sub> Receptor suppresses the osteoclast function, leading to increased bone density.<ref>{{cite journal | vauthors = He W, Wilder T, Cronstein BN | year = 2013 | title = Rolofylline, an adenosine A1 receptor antagonist, inhibits osteoclast differentiation as an inverse agonist | journal = Br J Pharmacol | volume = 170 | issue = 6| pages = 1167–1176 | doi = 10.1111/bph.12342 | pmc = 3838692 }}</ref>

===A<sub>2A</sub> adenosine receptor===
{{Main|Adenosine A2A receptor}}
As with the A<sub>1</sub>, the A<sub>2A</sub> receptors are believed to play a role in regulating myocardial oxygen consumption and coronary blood flow.

====Mechanism====
The activity of A<sub>2A</sub> adenosine receptor, a G-protein coupled receptor family member, is mediated by G proteins that activate [[adenylyl cyclase]]. It is abundant in basal ganglia, vasculature and platelets and it is a major target of caffeine.<ref name="entrez">{{cite web | title = Entrez Gene: ADORA2A adenosine A2A receptor| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=135}}</ref>

====Function====
The A<sub>2A</sub> receptor is responsible for regulating myocardial blood flow by [[vasodilation|vasodilating]] the [[coronary circulation|coronary arteries]], which increases blood flow to the [[myocardium]], but may lead to hypotension. Just as in A1 receptors, this normally serves as a protective mechanism, but may be destructive in altered cardiac function.

====Agonists and antagonists====
Specific antagonists include [[istradefylline]] (KW-6002) and [[SCH-58261]], while specific agonists include [[CGS-21680]] and ATL-146e.<ref name="pmid16518376">{{cite journal | vauthors = Jacobson KA, Gao ZG | title = Adenosine receptors as therapeutic targets | journal = Nature Reviews. Drug Discovery | volume = 5 | issue = 3 | pages = 247–64 | year = 2006 | pmid = 16518376 | doi = 10.1038/nrd1983 | pmc = 3463109 }}</ref>

====Bone homeostasis====
The role of A2A receptor opposes that of A1 in that it inhibits osteoclast differentiation and activates [[osteoblast]]s.<ref>{{cite journal | vauthors = Mediero A, Frenkel SR, Wilder T, HeW MA, Cronstein BN | year = 2012 | title = Adenosine A2A receptor activation prevents wearparticle-induced osteolysis | journal = Sci Transl Med | volume = 4 | issue = 135| pages = 135–165 }}</ref> Studies have shown it to be effective in decreasing inflammatory osteolysis in inflamed bone.<ref>{{cite journal | vauthors = Mediero A, Kara FM, Wilder T, Cronstein BN | year = 2012 | title = Adenosine A 2A receptor ligation inhibits osteoclast formation | journal = Am J Pathol | volume = 180 | issue = 2| pages = 775–786 | doi = 10.1016/j.ajpath.2011.10.017 |pmc=3349861  | doi-access = free }}</ref> This role could potentiate new therapeutic treatment in aid of bone regeneration and increasing bone volume.

===A<sub>2B</sub> adenosine receptor===
{{Main|Adenosine A2B receptor}}
This integral membrane protein stimulates adenylate cyclase activity in the presence of adenosine. This protein also interacts with [[netrin-1]], which is involved in axon elongation.

====Bone homeostasis====
Similarly to A2A receptor, the A2B receptor promotes osteoblast differentiation.<ref>{{cite journal | vauthors = Costa MA, Barbosa A, Neto E, Sá-e-Sousa A, Freitas R, Neves JM, Magalhães-Cardoso T, Ferreirinha F, Correia-de-Sá P | year = 2011 | title = On the role of subtype selective adenosine receptor agonists during proliferation and osteogenic differentiation of human primary bone marrow stromal cells | journal = J Cell Physiol | volume = 226 | issue = 5| pages = 1353–1366 | doi = 10.1002/jcp.22458 }}</ref> The osteoblast cell is derived from the Mesenchymal Stem Cell (MSC) which can also differentiate into a chondrocyte.<ref name="10.1017/erm.2013.2">{{cite journal | vauthors = Carroll SH, Ravid K | year = 2013 | title = Differentiation of mesenchymal stem cells to osteoblasts and chondrocytes: a focus on adenosine receptors | journal = Expert Reviews in Molecular Medicine | volume =  15| doi = 10.1017/erm.2013.2 | doi-access = free }}</ref> The cell signalling involved in the stimulation of the A2B receptor directs the route of differentiation to osteoblast, rather than chondrocyte via the Runx2 gene expression.<ref name="10.1017/erm.2013.2" /> Potential therapeutic application in aiding bone degenerative diseases, age related changes as well as injury repair.

===A<sub>3</sub> adenosine receptor===
{{Main|Adenosine A3 receptor}}
It has been shown in studies to inhibit some specific signal pathways of adenosine. It allows for the inhibition of growth in human melanoma cells. Specific antagonists include ''MRS1191'', ''MRS1523'' and ''MRE3008F20'', while specific agonists include [[Cl-IB-MECA]] and MRS3558.<ref name="pmid16518376" />

====Bone homeostasis====
The role of A3 receptor is less defined in this field. Studies have shown that it plays a role in the downregulation of [[osteoclast]]s.<ref>{{cite journal | vauthors = Rath-Wolfson L, Bar-Yehuda S, Madi L, Ochaion A, Cohen S, Zabutti A, Fishman P | year = 2006 | title = IB-MECA, an A | journal = Clin Exp Rheumatol | volume = 24 | pages = 400–406 }}</ref> Its function in regards to osteoblasts remains ambiguous.

==Ligand affinities==
===Adenosine receptor agonists===
{| class="wikitable"
|+ Binding affinities (K<sub>i</sub>, nM) of notable adenosine receptor agonists<ref name="KhayatHanifGeldenhuys2019">{{cite book | vauthors = Khayat MT, Hanif A, Geldenhuys WJ, Nayeem MA | chapter = Adenosine Receptors and Drug Discovery in the Cardiovascular System | pages=16–64 | veditors=Choudhary MI | title=Frontiers in Cardiovascular Drug Discovery: Volume 4 | publisher=Amazon Digital Services LLC - Kdp | series=Frontiers in Cardiovascular Drug Discovery  | year=2019 | isbn=978-1-68108-400-8 | url=https://books.google.com/books?id=R6SXDwAAQBAJ&pg=PA16 | access-date=23 September 2024}}</ref><ref>{{cite journal | vauthors = Müller CE, Jacobson KA | title = Recent developments in adenosine receptor ligands and their potential as novel drugs | journal = Biochim Biophys Acta | volume = 1808 | issue = 5 | pages = 1290–1308 | date = May 2011 | pmid = 21185259 | pmc = 3437328 | doi = 10.1016/j.bbamem.2010.12.017 | url = }}</ref>
|-
! Compound !! [[A1 receptor|A<sub>1</sub>]] !! [[A2A receptor|A<sub>2A</sub>]] !! [[A2B receptor|A<sub>2B</sub>]] !! [[A3 receptor|A<sub>3</sub>]] !! Selectivity
|-
| [[Adenosine]] || ~100 (h)<br />73 (r) || 310 (h)<br />150 (r) || 15,000 (h)<br />5100 (r) || 290 (h)<br />6500 (r) || Non-selective
|-
| [[2-Chloroadenosine]] || 6.7 (r) || 76 (r) || 24,000 (h) || 1890 (r) || A<sub>1</sub>-selective
|-
| [[CV-1808]] || 400 (r) || 100 (r) || {{Abbr|ND|No data}} || {{Abbr|ND|No data}} || {{Abbr|ND|No data}}
|-
| [[5′-(N-Ethylcarboxamido)adenosine|NECA]] || 14 (h)<br />5.1 (r) || 20 (h)<br />9.7 (r) || 140 (h)<br />1890 (h)<br />1900 (m) || 25 (h)<br />113 (r) || Non-selective
|-
| [[CGS-21680]] || 289 (h)<br />1800 (r)<br />120 (rb) || 27 (h)<br />19 (r) || >10,000 (h)<br />>10,000 (r) || 67 (h)<br />584 (r)<br />673 (rb) || A<sub>2A</sub>-selective
|-
| [[HENECA]] || 60 (h) || 6.4 (h) || 6100 || 2.4 (h) || Non-selective
|-
| [[BAY 60-6583]] || >10,000 (h) || >10,000 (h) || 3–10 (h)<br />330 (m)<br />750 (d)<br />340 (rb) || >10,000 (h) || A<sub>2B</sub>-selective
|-
| colspan="6" style="width: 1px; background-color:#eaecf0; text-align: center;" | '''Notes:''' Values are in nanomolar (nM) units. The smaller the value, the more avidly the compound binds to the site. The parentheses after values indicate the species: h = human, r = rat, m = mouse, rb = rabbit, d = dog.
|}

===Adenosine receptor antagonists===
{| class="wikitable"
|+ Binding affinities (K<sub>i</sub>, nM) of notable adenosine receptor antagonists<ref name="KhayatHanifGeldenhuys2019" /><ref>{{cite journal | vauthors = Müller CE, Jacobson KA | title = Xanthines as adenosine receptor antagonists | journal = Handb Exp Pharmacol | volume = | issue = 200 | pages = 151–199 | date = 2011 | pmid = 20859796 | pmc = 3882893 | doi = 10.1007/978-3-642-13443-2_6 | url = }}</ref>
|-
! Compound !! [[A1 receptor|A<sub>1</sub>]] !! [[A2A receptor|A<sub>2A</sub>]] !! [[A2B receptor|A<sub>2B</sub>]] !! [[A3 receptor|A<sub>3</sub>]] !! Selectivity
|-
| [[Caffeine]] || 10,700 (h)<br />44,900 (h)<br />41,000 (r)<br />44,000 (r)<br />47,000 (gp)<br />44,000 (c) || 23,400 (h)<br />9560 (h)<br />45,000 (r)<br />32,500 (r)<br />48,000 (r) || 33,800 (h)<br />10,400 (h)<br />20,500 (h)<br />30,000 (r)<br />13,000 (m) || 13,300 (h)<br />>100,000 (r) || Non-selective
|-
| [[Theophylline]] || 6770 (h)<br />14,000 (r)<br />8740 (r)<br />7060 (gp)<br />4710 (rb)<br />9050 (s)<br />6330 (c) || 1710 (h)<br />6700 (h)<br />22,000 (r)<br />25300 (r) || 9070 (h)<br />74,000 (h)<br />15,100 (r)<br />5630 (m)<br />11,000 (gp)<br />17,700 (rb)<br />38,700 (d) || 22,300 (h)<br />86,400 (h)<br />>100,000 (r)<br />85,000 (r)<br />>100,000 (d) || Non-selective
|-
| [[Theobromine]] || 105,000 (r)<br />83,400 (r) || >250,000 (r)<br />187,000 (r) || 130,000 (h) || >100,000 (r) || Non-selective
|-
| [[Paraxanthine]] || 21,000 (r) || 32,000 (r) || 4,500 (h) || >100,000 (r) || Non-selective
|-
| [[3-Chlorostyrylcaffeine]] (CSC) || 28,000 (r) || 54 (r) || 8200 || >10,000 (r) || A<sub>2A</sub>-selective
|-
| [[MSX-2]] || 900 (r)<br />2500 (h) || 8.04 (r)<br />5.38 (h)<br />14.5 (h) || >10,000 (h) || >10,000 (h) || A<sub>2A</sub>-selective
|-
| [[Istradefylline]] (KW-6002) || 841 (h)<br />230 (r) || 12 (h)<br />91.2 (h)<br />2.2 (r)<br />4.46 (r) || >10,000 (h) || 4470 (h) || A<sub>2A</sub>-selective
|-
| [[CGS-15943]] || 3.5 (h) || 1.2 (h) || 32.4 (h) || 35 (h) || Non-selective
|-
| [[SCH-58261]] || 725 (h) || 5.0 (h) || 1110 (h) || 1200 (h) || A<sub>2A</sub>-selective
|-
| [[ZM-241,385|ZM-241385]] || 255  || 0.8 || 50 || >10,000 || A<sub>2A</sub>-selective
|-
| [[Preladenant]] (SCH-420814) || >1000 (h) || 0.9 (h) || >1000 (h) || >1000 (h) || A<sub>2A</sub>-selective
|-
| colspan="6" style="width: 1px; background-color:#eaecf0; text-align: center;" | '''Notes:''' Values are in nanomolar (nM) units. The smaller the value, the more avidly the compound binds to the site. The parentheses after values indicate the species: h = human, r = rat, m = mouse, gp = guinea pig, rb = rabbit, c = calf or cow, s = sheep.
|}

==References ==
{{Reflist|2}}

==External links==
* {{cite web | url = http://www.iuphar-db.org/GPCR/ChapterMenuForward?chapterID=1273 | title = Adenosine Receptors | work = IUPHAR Database of Receptors and Ion Channels | publisher = International Union of Basic and Clinical Pharmacology | access-date = 2006-07-20 | archive-date = 2016-10-24 | archive-url = https://web.archive.org/web/20161024114822/http://www.iuphar-db.org/GPCR/ChapterMenuForward?chapterID=1273 | url-status = dead }}
*{{MeshName|Adenosine+Receptors}}

{{G protein-coupled receptors}}
{{Authority control}}

[[Category:G protein-coupled receptors]]
[[Category:Adenosine receptors| ]]