2020
DOI: 10.20944/preprints202004.0115.v1
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Adenosine-Related Mechanisms in Non-Adenosine Receptor Drugs

Abstract: Many ligands directly target adenosine receptors (ARs). Here we review the effects on adenosinergic signaling of other drugs that are not typically identified as binding ARs. Non-AR mechanisms include raising adenosine levels by inhibiting adenosine transport (e.g. ticagrelor, ethanol, cannabidiol), affecting intracellular metabolic pathways (e.g. methotrexate, nicotinamide riboside, salicylate, AICA riboside), or undetermined means (e.g. acupuncture). Yet other compounds bind ARs, in addition to their canonic… Show more

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Cited by 10 publications
(7 citation statements)
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“…This regimen has now been abandoned, but it has allowed us to identify multiple pathways activated by the drug chemical precursor, salicylate, which include an indirect elevation of extracellular Ado concentrations [ 53 ]. A similar indirect influence on the Ado system has been demonstrated for high doses of other NSAIDs (i.e., sulindac) and for sulfasalazine, a prodrug of 5-amino-salicylic acid acting as a DMARD [ 53 , 54 ].…”
Section: Drugs Targeting the Adenosine System In Autoimmune Disordmentioning
confidence: 60%
“…This regimen has now been abandoned, but it has allowed us to identify multiple pathways activated by the drug chemical precursor, salicylate, which include an indirect elevation of extracellular Ado concentrations [ 53 ]. A similar indirect influence on the Ado system has been demonstrated for high doses of other NSAIDs (i.e., sulindac) and for sulfasalazine, a prodrug of 5-amino-salicylic acid acting as a DMARD [ 53 , 54 ].…”
Section: Drugs Targeting the Adenosine System In Autoimmune Disordmentioning
confidence: 60%
“…AMPK activity has been described to prevent articular cartilage degeneration during mouse aging ( 257 ), and is also required to maintain mitochondrial function and prevent OA ( 213 ). As we have described earlier in this review, metformin can activate AMPK, resulting in an increase in extracellular adenosine ( 194 ). It is known that metformin is beneficial in obese patients with knee OA, but the contribution of AMPK to this effect requires further study.…”
Section: Discussionmentioning
confidence: 81%
“…Metformin, a first-line drug for T2D treatment, is known to affect the energy state of the cell. It has been recently proposed that metformin may be beneficial in obese patients with knee OA ( 193 ) and can also inhibit respiratory chain complex 1, activating AMPK and inhibiting AMP deaminase, which results in an increase in extracellular adenosine ( 194 ). The increased adenosine levels might activate A2AR and could explain the beneficial effect of metformin in obese patients with knee osteoarthritis, but this needs to be explored further.…”
Section: Purinergic System In Oa and Modulation By Metainflammationmentioning
confidence: 99%
“…The second step is an attempt to translate these in vitro findings to potential in vivo relevance by looking for accepted biomarkers of NT inhibition. As adenosine represents the main endogenous substrate of NTs, which are essential for adenosine re-uptake, extracellular adenosine levels can be elevated as a result of NT inhibition in vivo, although other mechanisms (e.g., inhibition of adenosine metabolism) can also result in elevated plasma adenosine levels [ 23 ]. Among the NT most relevant for adenosine re-uptake, ENT1 has been identified as a major player.…”
Section: Background and Role Of Nts And Their Inhibitionmentioning
confidence: 99%