Adenosine

In individuals with supraventricular tachycardia (SVT), adenosine is a first line treatment used to help identify and convert the rhythm.{{cite journal |vauthors=Ciriello GD, Sorice D, Orlando A, Papaccioli G, Colonna D, Correra A, Romeo E, Esposito R, De Marco M, Diana V, Giordano M, Barrile LS, Russo MG, Sarubbi B |title=Antiarrhythmic therapy for narrow QRS supraventricular tachyarrhythmias in newborns and infants in the first year of life: Potent tools to be handled with care |journal=Indian Pacing and Electrophysiology Journal |volume=24 |issue=5 |pages=271–281 |date=2024 |pmid=39033975 |pmc=11480843 |doi=10.1016/j.ipej.2024.07.005}}{{Cite journal | vauthors = Borea PA, Gessi S, Merighi S, Vincenzi F, Varani K | title = Pharmacology of Adenosine Receptors: The State of the Art | journal = Physiological Reviews | volume = 98 | issue = 3 | pages = 1591–1625 | date = July 2018 | pmid = 29848236 | doi = 10.1152/physrev.00049.2017 | s2cid = 44107679 | doi-access = free | hdl = 11392/2391482 | hdl-access = free }}{{Cite journal | vauthors = Delacrétaz E | title = Clinical practice. Supraventricular tachycardia | journal = The New England Journal of Medicine | volume = 354 | issue = 10 | pages = 1039–1051 | date = March 2006 | pmid = 16525141 | doi = 10.1056/NEJMcp051145 }}{{Cite journal | vauthors = Belhassen B, Pelleg A | title = Electrophysiologic effects of adenosine triphosphate and adenosine on the mammalian heart: clinical and experimental aspects | journal = Journal of the American College of Cardiology | volume = 4 | issue = 2 | pages = 414–424 | date = August 1984 | pmid = 6376597 | doi = 10.1016/S0735-1097(84)80233-8 | s2cid = 21575090 | doi-access = free }}

Certain SVTs can be successfully terminated with adenosine.{{Cite journal | vauthors = Mitchell J, Lazarenko G | title = Wide QRS complex tachycardia. Diagnosis: Supraventricular tachycardia with aberrant conduction; intravenous (IV) adenosine | journal = CJEM | volume = 10 | issue = 6 | pages = 572–3, 581 | date = November 2008 | pmid = 19000353 }} This includes any re-entrant arrhythmias that require the AV node for the re-entry, e.g., AV reentrant tachycardia (AVRT) and AV nodal reentrant tachycardia (AVNRT). In addition, atrial tachycardia can sometimes be terminated with adenosine.{{Cite book | vauthors = Goyal A, Basit H, Bhyan P, Zeltser R | chapter = Reentry Arrhythmia |date=2022| chapter-url= http://www.ncbi.nlm.nih.gov/books/NBK537089/|title = StatPearls|place=Treasure Island, FL |publisher=StatPearls Publishing|pmid=30725774|access-date=2022-01-28}}

Fast rhythms of the heart that are confined to the atria (e.g., atrial fibrillation and atrial flutter) or ventricles (e.g., monomorphic ventricular tachycardia), and do not involve the AV node as part of the re-entrant circuit, are not typically converted by adenosine. However, the ventricular response rate is temporarily slowed with adenosine in such cases.

Because of the effects of adenosine on AV node-dependent SVTs, adenosine is considered a class V antiarrhythmic agent. When adenosine is used to cardiovert an abnormal rhythm, it is normal for the heart to enter ventricular asystole for a few seconds. This can be disconcerting to a normally conscious patient, and is associated with angina-like sensations in the chest.{{Cite book|title=Coronary Pressure| vauthors = Pijls NH, De Bruyne B |year=2000|publisher=Springer|isbn=0-7923-6170-9 }}{{page needed|date=August 2019}}

Adenosine is used as an adjunct to thallium (TI 201) or technetium (Tc99m) myocardial perfusion scintigraphy (nuclear stress test) in patients unable to undergo adequate stress testing with exercise.{{Cite journal | vauthors = O'Keefe JH, Bateman TM, Silvestri R, Barnhart C | title = Safety and diagnostic accuracy of adenosine thallium-201 scintigraphy in patients unable to exercise and those with left bundle branch block | journal = American Heart Journal | volume = 124 | issue = 3 | pages = 614–621 | date = September 1992 | pmid = 1514488 | doi = 10.1016/0002-8703(92)90268-z }}

When used to treat SVT, adenosine is administered intravenously as a rapid bolus (typically 0.10–0.15 mg/kg initially) over 1-2 seconds, followed by a rapid saline flush (often using a 2-way or 3-way stopcock). If the initial dose is ineffective, it may be repeated every 2 minutes with a slightly increased dose (0.05–0.1 mg/kg increments) every 2 minutes up to a maximum total dose of 0.3 mg/kg (not exceeding 12 mg). Due to adenosine's extremely short half-life (less than 10 seconds), it is often injected through a central venous line or a large proximal peripheral vein; administration into lower extremities, PICC lines, or smaller veins may lead to therapeutic failure due to rapid metabolism before reaching the heart. When given to dilate the arteries, such as in a "stress test", the dosage is typically 0.14 mg/kg/min, administered for 4 or 6 minutes, depending on the protocol.

The recommended dose may be increased in patients on theophylline since methylxanthines prevent binding of adenosine at receptor sites. The dose is often decreased in patients on dipyridamole (Persantine) and diazepam (Valium) because adenosine potentiates the effects of these drugs. The recommended dose is also reduced by half in patients presenting congestive heart failure, myocardial infarction, shock, hypoxia, and/or chronic liver disease or chronic kidney disease, and in elderly patients.

Adverse effects associated with adenosine administration are primarily due to its activation of adenosine receptors on vascular tissue, resulting in vasodilation. Side effects of adenosine include skin flushing, lightheadedness, nausea, sweating, nervousness, numbness, and a sense of impending doom. These effects are typically very short-lived due to adenosine's rapid metabolism and short half-life. Less common, but more serious, cardiovascular effects can occur, such as cardiac arrhythmias (including premature atrial and ventricular contractions and atrioventricular (AV) block), hypotension, cardiac ischemia, and prolonged asystole.{{cite web |vauthors=Singh S, McKintosh R |title=Adenosine |publisher=StatPearls Publishing |date=August 28, 2023 |pmid=30085591 |url=https://www.ncbi.nlm.nih.gov/books/NBK519049/ |access-date=January 30, 2025}}

Dipyridamole potentiates the action of adenosine, requiring the use of lower doses.

File:Caffeine and adenosine.svg's principal mode of action is as an antagonist of adenosine receptors in the brain.{{cite journal | vauthors = Saygin D, Tabib T, Bittar HE, Valenzi E, Sembrat J, Chan SY, Rojas M, Lafyatis R | title = Transcriptional profiling of lung cell populations in idiopathic pulmonary arterial hypertension | journal = Pulmonary Circulation | volume = 10 | issue = 1 | pages = 1–15 | date = 2020 | pmid = 32166015 | doi = 10.1177/2045894020908782 | pmc = 7052475 }}]]

Methylxanthines (e.g. caffeine found in coffee, theophylline found in tea, or theobromine found in chocolate) have a purine structure and bind to some of the same receptors as adenosine.{{Cite journal | vauthors = Ribeiro JA, Sebastião AM | title = Caffeine and adenosine | journal = Journal of Alzheimer's Disease | volume = 20 | issue = Suppl 1 | pages = S3-15 | year = 2010 | pmid = 20164566 | doi = 10.3233/JAD-2010-1379 | doi-access = free | hdl = 10451/6361 | hdl-access = free }} Methylxanthines act as competitive antagonists of adenosine and can blunt its pharmacological effects.{{Cite web| title=Vitamin B4 |publisher=R&S Pharmchem |url=http://www.rspharmchem.com/vitamin-b4.htm |date=April 2011 |url-status=dead |archive-url=https://web.archive.org/web/20110715213918/http://www.rspharmchem.com/vitamin-b4.htm |archive-date= 2011-07-15 }} Individuals taking large quantities of methylxanthines may require increased doses of adenosine.

Caffeine acts by blocking binding of adenosine to the adenosine A₁ receptor, which enhances release of the neurotransmitter acetylcholine.{{Cite journal | vauthors = Carter AJ, O'Connor WT, Carter MJ, Ungerstedt U | title = Caffeine enhances acetylcholine release in the hippocampus in vivo by a selective interaction with adenosine A1 receptors | journal = The Journal of Pharmacology and Experimental Therapeutics | volume = 273 | issue = 2 | pages = 637–642 | date = May 1995 | doi = 10.1016/S0022-3565(25)09521-7 | pmid = 7752065 }} Caffeine also increases cyclic AMP levels through nonselective inhibition of phosphodiesterase.{{Cite journal | vauthors = Faudone G, Arifi S, Merk D | title = The Medicinal Chemistry of Caffeine | journal = Journal of Medicinal Chemistry | volume = 64 | issue = 11 | pages = 7156–7178 | date = June 2021 | pmid = 34019396 | doi = 10.1021/acs.jmedchem.1c00261 | s2cid = 235094871 }} "Caffeine has a three-dimensional structure similar to that of adenosine," which allows it to bind and block its receptors.{{Cite book | vauthors = Hillis DM, Sadava D, Hill RW, Price MV | title = Principles of Life | edition = 2 | pages = 102–103 | year = 2015 | publisher = Macmillan Learning | isbn = 978-1-4641-8652-3 }}

Common contraindications for adenosine include

• Asthma, traditionally considered an absolute contraindication. This is being contested, and it is now considered a relative contraindication (however, selective adenosine antagonists are being investigated for use in treatment of asthma){{Cite journal | vauthors = Brown RA, Spina D, Page CP | title = Adenosine receptors and asthma | journal = British Journal of Pharmacology | volume = 153 | issue = Suppl 1 | pages = S446–S456 | date = March 2008 | pmid = 18311158 | pmc = 2268070 | doi = 10.1038/bjp.2008.22 }}

Adenosine is an endogenous purine nucleoside that modulates many physiological processes. Cellular signaling by adenosine occurs through four known adenosine receptor subtypes (A₁, A_2A, A_2B, and A₃).{{Cite journal | vauthors = Haskó G, Linden J, Cronstein B, Pacher P | title = Adenosine receptors: therapeutic aspects for inflammatory and immune diseases | journal = Nature Reviews. Drug Discovery | volume = 7 | issue = 9 | pages = 759–770 | date = September 2008 | pmid = 18758473 | pmc = 2568887 | doi = 10.1038/nrd2638 }}

Extracellular adenosine concentrations from normal cells are approximately 300 nM; however, in response to cellular damage (e.g., in inflammatory or ischemic tissue), these concentrations are quickly elevated (600–1,200 nM). Thus, in regard to stress or injury, the function of adenosine is primarily that of cytoprotection preventing tissue damage during instances of hypoxia, ischemia, and seizure activity. Activation of A_2A receptors produces a constellation of responses that in general can be classified as anti-inflammatory.{{Cite journal | vauthors = Haskó G, Cronstein BN | title = Adenosine: an endogenous regulator of innate immunity | journal = Trends in Immunology | volume = 25 | issue = 1 | pages = 33–39 | date = January 2004 | pmid = 14698282 | doi = 10.1016/j.it.2003.11.003 }} Enzymatic production of adenosine can be anti-inflammatory or immunosuppressive.{{Cite journal | vauthors = Sek K, Mølck C, Stewart GD, Kats L, Darcy PK, Beavis PA | title = Targeting Adenosine Receptor Signaling in Cancer Immunotherapy | journal = International Journal of Molecular Sciences | volume = 19 | issue = 12 | pages = 3837 | date = December 2018 | pmid = 30513816 | pmc = 6321150 | doi = 10.3390/ijms19123837 | doi-access = free }}{{Cite journal | vauthors = Konen JM, Fradette JJ, Gibbons DL | title = The Good, the Bad and the Unknown of CD38 in the Metabolic Microenvironment and Immune Cell Functionality of Solid Tumors | journal = Cells | volume = 9 | issue = 1 | pages = 52 | date = December 2019 | pmid = 31878283 | pmc = 7016859 | doi = 10.3390/cells9010052 | doi-access = free }}{{Cite journal | vauthors = Antonioli L, Pacher P, Vizi ES, Haskó G | title = CD39 and CD73 in immunity and inflammation | journal = Trends in Molecular Medicine | volume = 19 | issue = 6 | pages = 355–367 | date = June 2013 | pmid = 23601906 | pmc = 3674206 | doi = 10.1016/j.molmed.2013.03.005 }}

{{Main|Adenosine receptor}}

All adenosine receptor subtypes (A₁, A_2A, A_2B, and A₃) are G-protein-coupled receptors. The four receptor subtypes are further classified based on their ability to either stimulate or inhibit adenylate cyclase activity. The A₁ receptors couple to G_i/o and decrease cAMP levels, while the A₂ adenosine receptors couple to G_s, which stimulates adenylate cyclase activity. In addition, A₁ receptors couple to G_o, which has been reported to mediate adenosine inhibition of Ca²⁺ conductance, whereas A_2B and A₃ receptors also couple to G_q and stimulate phospholipase activity.

Researchers at Cornell University have recently shown adenosine receptors to be key in opening the blood-brain barrier (BBB).

Mice dosed with adenosine have shown increased transport across the BBB of amyloid plaque antibodies and prodrugs associated with Parkinson's disease, Alzheimer's, multiple sclerosis, and cancers of the central nervous system.{{Cite journal | vauthors = Carman AJ, Mills JH, Krenz A, Kim DG, Bynoe MS | title = Adenosine receptor signaling modulates permeability of the blood-brain barrier | journal = The Journal of Neuroscience | volume = 31 | issue = 37 | pages = 13272–13280 | date = September 2011 | pmid = 21917810 | pmc = 3328085 | doi = 10.1523/JNEUROSCI.3337-11.2011 }}

Adenosine is an endogenous agonist of the ghrelin/growth hormone secretagogue receptor.{{Cite book | vauthors = Smith RG, Betancourt L, Sun Y | chapter = Role of the Growth Hormone Secretagogue Receptor in the Central Nervous System | veditors = Kordon C, Robinson I, Hanoune J, Dantzer R |title=Brain Somatic Cross-Talk and the Central Control of Metabolism| chapter-url = https://books.google.com/books?id=Ml7vCAAAQBAJ&pg=PA42|year= 2012|publisher=Springer Science & Business Media|isbn=978-3-642-18999-9|pages=42–}} However, while it is able to increase appetite, unlike other agonists of this receptor, adenosine is unable to induce the secretion of growth hormone and increase its plasma levels.

When it is administered intravenously, adenosine causes transient heart block in the atrioventricular (AV) node. This is mediated via the A₁ receptor, inhibiting adenylyl cyclase, reducing cAMP and so causing cell hyperpolarization by increasing K⁺ efflux via inward rectifier K⁺ channels, subsequently inhibiting Ca²⁺ current.{{Cite web|date=2021-03-18|title=Аденозин в косметике - Польза антивозрастной корейской косметики|url=https://kimito.com.ua/adenozin-v-kosmetike/|access-date=2021-03-22|website=KIMITO|language=ru-RU}}{{Cite book|title = Basic & Clinical Pharmacology |edition=12th| vauthors = Katzung B |publisher = McGraw Hill|year = 2012|page=245|isbn = 978-0-07-176402-5}} It also causes endothelial-dependent relaxation of smooth muscle as is found inside the artery walls. This causes dilation of the "normal" segments of arteries, i.e. where the endothelium is not separated from the tunica media by atherosclerotic plaque. This feature allows physicians to use adenosine to test for blockages in the coronary arteries, by exaggerating the difference between the normal and abnormal segments.

The administration of adenosine also reduces blood flow to coronary arteries past the occlusion. Other coronary arteries dilate when adenosine is administered while the segment past the occlusion is already maximally dilated, which is a process called coronary steal. This leads to less blood reaching the ischemic tissue, which in turn produces the characteristic chest pain.

Adenosine used as a second messenger can be the result of de novo purine biosynthesis via adenosine monophosphate (AMP), though it is possible other pathways exist.{{Cite journal | vauthors = Miller-Patrick K, Vincent DL, Early RJ, Weems YS, Tanaka Y, Ashimine DT, Nusser KD, Lee CN, Ledgerwood KS, Weems CW | title = Effects of the purine biosynthesis pathway inhibitors azaserine, hadacidin, and mycophenolic acid on the developing ovine corpus luteum | journal = The Chinese Journal of Physiology | volume = 36 | issue = 4 | pages = 245–252 | year = 1993 | pmid = 8020339 }}

When adenosine enters the circulation, it is broken down by adenosine deaminase, which is present in red blood cells and the vessel wall.

Dipyridamole, an inhibitor of adenosine nucleoside transporter, allows adenosine to accumulate in the blood stream. This causes an increase in coronary vasodilatation.

Adenosine deaminase deficiency is a known cause of immunodeficiency.

{{See also|Nucleoside analogue}}

The adenosine analog NITD008 has been reported to directly inhibit the recombinant RNA-dependent RNA polymerase of the dengue virus by terminating its RNA chain synthesis. This interaction suppresses peak viremia and rise in cytokines and prevents lethality in infected animals, raising the possibility of a new treatment for this flavivirus.{{Cite journal | vauthors = Yin Z, Chen YL, Schul W, Wang QY, Gu F, Duraiswamy J, Kondreddi RR, Niyomrattanakit P, Lakshminarayana SB, Goh A, Xu HY, Liu W, Liu B, Lim JY, Ng CY, Qing M, Lim CC, Yip A, Wang G, Chan WL, Tan HP, Lin K, Zhang B, Zou G, Bernard KA, Garrett C, Beltz K, Dong M, Weaver M, He H, Pichota A, Dartois V, Keller TH, Shi PY | title = An adenosine nucleoside inhibitor of dengue virus | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 106 | issue = 48 | pages = 20435–20439 | date = December 2009 | pmid = 19918064 | pmc = 2787148 | doi = 10.1073/pnas.0907010106 | doi-access = free | bibcode = 2009PNAS..10620435Y }} The 7-deaza-adenosine analog has been shown to inhibit the replication of the hepatitis C virus.{{Cite journal | vauthors = Olsen DB, Eldrup AB, Bartholomew L, Bhat B, Bosserman MR, Ceccacci A, Colwell LF, Fay JF, Flores OA, Getty KL, Grobler JA, LaFemina RL, Markel EJ, Migliaccio G, Prhavc M, Stahlhut MW, Tomassini JE, MacCoss M, Hazuda DJ, Carroll SS | title = A 7-deaza-adenosine analog is a potent and selective inhibitor of hepatitis C virus replication with excellent pharmacokinetic properties | journal = Antimicrobial Agents and Chemotherapy | volume = 48 | issue = 10 | pages = 3944–3953 | date = October 2004 | pmid = 15388457 | pmc = 521892 | doi = 10.1128/AAC.48.10.3944-3953.2004 }} BCX4430 is protective against Ebola and Marburg viruses.{{Cite journal | vauthors = Warren TK, Wells J, Panchal RG, Stuthman KS, Garza NL, Van Tongeren SA, Dong L, Retterer CJ, Eaton BP, Pegoraro G, Honnold S, Bantia S, Kotian P, Chen X, Taubenheim BR, Welch LS, Minning DM, Babu YS, Sheridan WP, Bavari S | title = Protection against filovirus diseases by a novel broad-spectrum nucleoside analogue BCX4430 | journal = Nature | volume = 508 | issue = 7496 | pages = 402–405 | date = April 2014 | pmid = 24590073 | pmc = 7095208 | doi = 10.1038/nature13027 | bibcode = 2014Natur.508..402W }} Such adenosine analogs are potentially clinically useful since they can be taken orally.

Adenosine is believed to be an anti-inflammatory agent at the A_2A receptor.{{Cite journal | vauthors = Nakav S, Chaimovitz C, Sufaro Y, Lewis EC, Shaked G, Czeiger D, Zlotnik M, Douvdevani A | title = Anti-inflammatory preconditioning by agonists of adenosine A1 receptor | journal = PLOS ONE | volume = 3 | issue = 5 | pages = e2107 | date = May 2008 | pmid = 18461129 | pmc = 2329854 | doi = 10.1371/journal.pone.0002107 | veditors = Bozza P | doi-access = free | bibcode = 2008PLoSO...3.2107N }}{{Cite journal | vauthors = Trevethick MA, Mantell SJ, Stuart EF, Barnard A, Wright KN, Yeadon M | title = Treating lung inflammation with agonists of the adenosine A2A receptor: promises, problems and potential solutions | journal = British Journal of Pharmacology | volume = 155 | issue = 4 | pages = 463–474 | date = October 2008 | pmid = 18846036 | pmc = 2579671 | doi = 10.1038/bjp.2008.329 }} Topical treatment of adenosine to foot wounds in diabetes mellitus has been shown in lab animals to drastically increase tissue repair and reconstruction. Topical administration of adenosine for use in wound-healing deficiencies and diabetes mellitus in humans is currently under clinical investigation.

Methotrexate's anti-inflammatory effect may be due to its stimulation of adenosine release.{{Cite journal | vauthors = Cronstein B | title = How does methotrexate suppress inflammation? | journal = Clinical and Experimental Rheumatology | volume = 28 | issue = 5 Suppl 61 | pages = S21–S23 | year = 2010 | pmid = 21044428 }}

In general, adenosine has an inhibitory effect in the central nervous system (CNS).

Caffeine's stimulatory effects are credited primarily (although not entirely) to its capacity to block adenosine receptors, thereby reducing the inhibitory tonus of adenosine in the CNS. This reduction in adenosine activity leads to increased activity of the neurotransmitters dopamine and glutamate.{{Cite journal | vauthors = Solinas M, Ferré S, You ZB, Karcz-Kubicha M, Popoli P, Goldberg SR | title = Caffeine induces dopamine and glutamate release in the shell of the nucleus accumbens | journal = The Journal of Neuroscience | volume = 22 | issue = 15 | pages = 6321–6324 | date = August 2002 | pmid = 12151508 | pmc = 6758129 | doi = 10.1523/JNEUROSCI.22-15-06321.2002 }} Experimental evidence suggests that adenosine and adenosine agonists can activate Trk receptor phosphorylation through a mechanism that requires the adenosine A_2A receptor.{{Cite journal | vauthors = Lee FS, Chao MV | title = Activation of Trk neurotrophin receptors in the absence of neurotrophins | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 98 | issue = 6 | pages = 3555–3560 | date = March 2001 | pmid = 11248116 | pmc = 30691 | doi = 10.1073/pnas.061020198 | doi-access = free | bibcode = 2001PNAS...98.3555L }}

Adenosine has been shown to promote thickening of hair on people with thinning hair.{{Cite journal | vauthors = Oura H, Iino M, Nakazawa Y, Tajima M, Ideta R, Nakaya Y, Arase S, Kishimoto J | title = Adenosine increases anagen hair growth and thick hairs in Japanese women with female pattern hair loss: a pilot, double-blind, randomized, placebo-controlled trial | journal = The Journal of Dermatology | volume = 35 | issue = 12 | pages = 763–767 | date = December 2008 | pmid = 19239555 | doi = 10.1111/j.1346-8138.2008.00564.x | s2cid = 12289511 }}{{Cite journal | vauthors = Hwang KA, Hwang YL, Lee MH, Kim NR, Roh SS, Lee Y, Kim CD, Lee JH, Choi KC | title = Adenosine stimulates growth of dermal papilla and lengthens the anagen phase by increasing the cysteine level via fibroblast growth factors 2 and 7 in an organ culture of mouse vibrissae hair follicles | journal = International Journal of Molecular Medicine | volume = 29 | issue = 2 | pages = 195–201 | date = February 2012 | pmid = 22020741 | doi = 10.3892/ijmm.2011.817 | doi-access = free }} A 2013 study compared topical adenosine with minoxidil in male androgenetic alopecia, finding it was as potent as minoxidil (in overall treatment outcomes) but with higher satisfaction rate with patients due to “faster prevention of hair loss and appearance of the newly grown hairs” (further trials were called for to clarify the findings).{{Cite journal | vauthors = Faghihi G, Iraji F, Rajaee Harandi M, Nilforoushzadeh MA, Askari G | title = Comparison of the efficacy of topical minoxidil 5% and adenosine 0.75% solutions on male androgenetic alopecia and measuring patient satisfaction rate | journal = Acta Dermatovenerologica Croatica | volume = 21 | issue = 3 | pages = 155–159 | date = 2013 | pmid = 24183218 }}

Adenosine is a key factor in regulating the body's sleep-wake cycle.{{cite journal | vauthors = Reichert CF, Deboer T, Landolt HP | title = Adenosine, caffeine, and sleep-wake regulation: state of the science and perspectives | journal = Journal of Sleep Research | volume = 31 | issue = 4 | pages = e13597 | date = August 2022 | pmid = 35575450 | pmc = 9541543 | doi = 10.1111/jsr.13597 }} Adenosine levels build up in the brain during periods of wakefulness, causing a need to sleep when level become too high and lowers during periods of sleep, giving a sensation of restedness when waking. Higher adenosine levels correlate with a stronger feeling of sleepiness, also known as sleep drive or sleep pressure.{{Cite web |date=2022-06-07 |title=Adenosine and Sleep |url=https://www.sleepfoundation.org/how-sleep-works/adenosine-and-sleep |access-date=2023-04-12 |website=Sleep Foundation |language=en-US}} Cognitive behavioral therapy for insomnia (CBT-I), which is considered one of the most effective treatments for insomnia, utilizes short-term sleep deprivation to raise and regulate adenosine levels in the body, for the intended promotion of consistent and sustained sleep in the long term.{{cite journal | vauthors = Perlis M, Shaw PJ, Cano G, Espie CA | title = Models of insomnia. | journal = Principles and Practice of Sleep Medicine. | date = January 2011 | volume = 5 | issue = 1 | pages = 850–865 | publisher = Elsevier Inc. | doi = 10.1016/B978-1-4160-6645-3.00078-5 | isbn = 9781416066453 | url = https://www.med.upenn.edu/cbti/assets/user-content/documents/ppsmmodelsofinsomnia20115theditionproof.pdf }}

A principal component of cannabis delta-9-tetrahydrocannabinol (THC) and the endocannabinoid anandamide (AEA) induces sleep in rats by increasing adenosine levels in the basal forebrain. These components also significantly increase slow-wave sleep during the sleep cycle, mediated by CB1 receptor activation. These findings identify a potential therapeutic use of cannabinoids to induce sleep in conditions where sleep may be severely attenuated.{{Cite journal | vauthors = Murillo-Rodriguez E, Blanco-Centurion C, Sanchez C, Piomelli D, Shiromani PJ | title = Anandamide enhances extracellular levels of adenosine and induces sleep: an in vivo microdialysis study | journal = Sleep | volume = 26 | issue = 8 | pages = 943–947 | date = December 2003 | pmid = 14746372 | doi = 10.1093/sleep/26.8.943 | doi-access = free }}

It also plays a role in regulation of blood flow to various organs through vasodilation.{{Cite journal | vauthors = Sato A, Terata K, Miura H, Toyama K, Loberiza FR, Hatoum OA, Saito T, Sakuma I, Gutterman DD | title = Mechanism of vasodilation to adenosine in coronary arterioles from patients with heart disease | journal = American Journal of Physiology. Heart and Circulatory Physiology | volume = 288 | issue = 4 | pages = H1633–H1640 | date = April 2005 | pmid = 15772334 | doi = 10.1152/ajpheart.00575.2004 | s2cid = 71178 }}{{Cite journal | vauthors = Costa F, Biaggioni I | title = Role of nitric oxide in adenosine-induced vasodilation in humans | journal = Hypertension | volume = 31 | issue = 5 | pages = 1061–1064 | date = May 1998 | pmid = 9576114 | doi = 10.1161/01.HYP.31.5.1061 | doi-access = free }}{{Cite journal | vauthors = Morgan JM, McCormack DG, Griffiths MJ, Morgan CJ, Barnes PJ, Evans TW | title = Adenosine as a vasodilator in primary pulmonary hypertension | journal = Circulation | volume = 84 | issue = 3 | pages = 1145–1149 | date = September 1991 | pmid = 1884445 | doi = 10.1161/01.CIR.84.3.1145 | doi-access = free }}

• Adenosine receptor
• Adenosine reuptake inhibitor
• List of growth hormone secretagogues

{{Reflist|30em}}

{{Neurotransmitters}}

{{Emergency medicine}}

{{Nucleobases, nucleosides, and nucleotides}}

{{Antiarrhythmic agents}}

{{Purine receptor modulators}}

{{GH/IGF-1 axis signaling modulators}}

{{Authority control}}

Category:Adenosine receptor agonists

Category:Antiarrhythmic agents

Category:Chemical substances for emergency medicine

Category:Drugs acting on the cardiovascular system

Category:Ghrelin receptor agonists

Category:Nucleosides

Category:Purines

Category:Neurotransmitters

Category:Vasodilators

Category:Hydroxymethyl compounds