Adenosine-Related Mechanisms in Non-Adenosine Receptor Drugs

Kenneth A. Jacobson; Marc L. Reitman

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preprints.org > medicine and pharmacology > pharmacology and toxicology > 202004.0115.v2

Working Paper Review Version 2 This version is not peer-reviewed

Adenosine-Related Mechanisms in Non-Adenosine Receptor Drugs

Kenneth A. Jacobson

^* and

Marc L. Reitman

Version 1 : Received: 6 April 2020 / Approved: 8 April 2020 / Online: 8 April 2020 (04:11:27 CEST)
Version 2 : Received: 8 April 2020 / Approved: 9 April 2020 / Online: 9 April 2020 (16:19:14 CEST)

A peer-reviewed article of this Preprint also exists.

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

Abstract

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, cannabidiol), affecting intracellular metabolic pathways (e.g. methotrexate, nicotinamide riboside, salicylate, 5‐aminoimidazole‐4‐carboxamide riboside), or undetermined means (e.g. acupuncture). Yet 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 in 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.

Keywords

adenosine receptor; nucleoside transport; CNS; inflammation; cardiovascular system; pain

Subject

Medicine and Pharmacology, Pharmacology and Toxicology

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Comments (1)

Comment 1

Received: 9 April 2020
Commenter: Kenneth Jacobson
Commenter's Conflict of Interests: Author

Comment: Many more mentions of ligands, their concentrations and mode of administration from the cited papers are now included in the text. This allows the reader to follow, in brief, how the various ligand probes were used in many of the studies and the strength of their findings. The Table was simplified by omitting 5 compounds, and minor corrections were made.

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