Editing Adenosine (section)

== Research ==

=== Viruses ===
{{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 [[cytokine]]s and prevents lethality in infected animals, raising the possibility of a new treatment for this [[flavivirus]].<ref>{{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 }}</ref> The 7-deaza-adenosine analog has been shown to inhibit the replication of the [[hepatitis C virus]].<ref>{{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 }}</ref> [[BCX4430]] is protective against [[Ebola virus disease|Ebola]] and [[Marburg virus disease|Marburg]] viruses.<ref>{{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 }}</ref> Such adenosine analogs are potentially clinically useful since they can be taken orally.

=== Anti-inflammatory properties ===
Adenosine is believed to be an [[anti-inflammatory]] agent at the A<sub>2A</sub> receptor.<ref name="pmid18461129">{{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 }}</ref><ref name="pmid18846036">{{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 }}</ref> 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.<ref name="pmid21044428">{{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 }}</ref>

=== Central nervous system ===
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 [[neurotransmitter]]s [[dopamine]] and [[glutamate]].<ref>{{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 }}</ref> Experimental evidence suggests that adenosine and adenosine agonists can activate [[Trk receptor]] phosphorylation through a mechanism that requires the adenosine A<sub>2A</sub> receptor.<ref name="pmid11248116">{{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 }}</ref>

=== Hair ===
Adenosine has been shown to promote thickening of hair on people with thinning hair.<ref name="pmid19239555">{{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 }}</ref><ref name="pmid22020741">{{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 }}</ref>  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).<ref>{{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 }}</ref>

=== Sleep ===
Adenosine is a key factor in regulating the body's [[Circadian rhythm|sleep-wake cycle]].<ref>{{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 }}</ref> Adenosine levels bulid 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.<ref>{{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}}</ref> [[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.<ref>{{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 }}</ref> 

A principal component of [[Cannabis (drug)|cannabis]] [[Tetrahydrocannabinol|delta-9-tetrahydrocannabinol]] (THC) and the [[Endocannabinoid system|endocannabinoid]] [[anandamide]] (AEA) induces [[sleep]] in [[rat]]s by increasing adenosine levels in the [[basal forebrain]]. These components also significantly increase [[slow-wave sleep]] during the [[sleep cycle]], mediated by [[CB1 receptor]] [[Cannabinoid agonist|activation]]. These findings identify a potential [[Medical cannabis|therapeutic use]] of [[cannabinoid]]s to induce sleep in conditions where sleep may be severely attenuated.<ref>{{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 }}</ref>