title: Pharmacological targeting of adenosine receptor signaling.
abstract: Adenosine receptor signaling plays important roles in normal physiology, but is also known to modulate the development or progression of several different diseases. The design of new, efficient, and safe pharmacological approaches to target the adenosine system may have considerable therapeutic potential, but is also associated with many challenges. This review summarizes the main challenges of adenosine receptor targeted treatment including tolerance, disease stage, cell type-specific effects, caffeine intake, adenosine level assessment and receptor distribution in vivo. Moreover, we discuss several potential ways to overcome these obstacles (i.e., the use of partial agonists, indirect receptor targeting, allosteric enhancers, prodrugs, non-receptor-mediated effects, neoreceptors, conditional knockouts). It is important to address these concerns during development of new and successful therapeutic approaches targeting the adenosine system.
authors.affiliation: Department of Physiology and Pharmacology, Karolinska Institutet, Sweden.
authors.forename: Maria
authors.initials: M
authors.lastname: Peleli
authors.affiliation: Department of Physiology and Pharmacology, Karolinska Institutet, Sweden.
authors.forename: Bertil B
authors.initials: BB
authors.lastname: Fredholm
authors.affiliation: Cellular and Molecular Physiology Laboratory (CMPL), Division of Obstetrics and Gynaecology, School of Medicine, Faculty of Medicine, Pontificia Universidad Católica de Chile, Santiago 8330024, Chile; Department of Physiology, Faculty of Pharmacy, Universidad de Sevilla, Seville E-41012, Spain; University of Queensland Centre for Clinical Research (UQCCR), Faculty of Medicine and Biomedical Sciences, University of Queensland, Herston, QLD 4029, Queensland, Australia.
authors.forename: Luis
authors.initials: L
authors.lastname: Sobrevia
authors.affiliation: Department of Physiology and Pharmacology, Karolinska Institutet, Sweden. Electronic address: mattias.carlstrom@ki.se.
authors.forename: Mattias
authors.initials: M
authors.lastname: Carlström
mesh_terms: D000241:Adenosine / Q000819:agonists / Q000037:antagonists & inhibitors / Q000235:genetics; D001928:Brain Diseases, Metabolic / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D058990:Molecular Targeted Therapy; D011355:Prodrugs / Q000627:therapeutic use; D058906:Purinergic P1 Receptor Agonists / Q000627:therapeutic use*; D058915:Purinergic P1 Receptor Antagonists / Q000627:therapeutic use*; D018047:Receptors, Purinergic P1 / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D011355:Prodrugs; D058906:Purinergic P1 Receptor Agonists; D058915:Purinergic P1 Receptor Antagonists; D018047:Receptors, Purinergic P1; D000241:Adenosine
keywords: Adenosine; Adenosine receptor; Disease; Drug discovery; Drug target; Pharmacology