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Open AccessFeature PaperReview

Adenosine-Related Mechanisms in Non-Adenosine Receptor Drugs

1
Molecular Recognition Section, Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD 20892, USA
2
Diabetes, Endocrinology and Obesity Branch, National Institute of Diabetes and Digestive and Kidney Diseases, NIH, Bethesda, MD 20892, USA
*
Author to whom correspondence should be addressed.
Cells 2020, 9(4), 956; https://doi.org/10.3390/cells9040956
Received: 10 March 2020 / Revised: 8 April 2020 / Accepted: 10 April 2020 / Published: 13 April 2020
(This article belongs to the Special Issue Adenosine Receptors: From Cell Biology to Human Diseases)
Many ligands directly target adenosine receptors (ARs). Here we review the effects of noncanonical AR drugs on adenosinergic signaling. Non-AR mechanisms include raising adenosine levels by inhibiting adenosine transport (e.g., ticagrelor, ethanol, and cannabidiol), affecting intracellular metabolic pathways (e.g., methotrexate, nicotinamide riboside, salicylate, and 5-aminoimidazole-4-carboxamide riboside), or undetermined means (e.g., acupuncture). However, other compounds bind ARs in addition to their canonical ‘on-target’ activity (e.g., mefloquine). The strength of experimental support for an adenosine-related role in a drug’s effects varies widely. AR knockout mice are the ‘gold standard’ method for investigating an AR role, but few drugs have been tested on these mice. Given the interest in AR modulation for treatment of cancer, CNS, immune, metabolic, cardiovascular, and musculoskeletal conditions, it is informative to consider AR and non-AR adenosinergic effects of approved drugs and conventional treatments. View Full-Text
Keywords: adenosine receptor; nucleoside transport; CNS; inflammation; cardiovascular system; pain adenosine receptor; nucleoside transport; CNS; inflammation; cardiovascular system; pain
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MDPI and ACS Style

Jacobson, K.A.; Reitman, M.L. Adenosine-Related Mechanisms in Non-Adenosine Receptor Drugs. Cells 2020, 9, 956.

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