A2A Receptor Ligands: Past, Present and Future Trends

Manera, Clementina; Saccomanni, Giuseppe

doi:10.2174/156802610791268765

Cited by 23 publications

(11 citation statements)

References 138 publications

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“…The SARs of ligands at the A 2A AR have been reviewed recently [38,39]. Substitution of adenosine at the 2-position, especially with (thio)ethers, secondary amines, and alkynes, has resulted in many synthetic analogues selective for the A 2A AR.…”

Section: Adenosine Receptor Agonistsmentioning

confidence: 99%

Recent developments in adenosine receptor ligands and their potential as novel drugs

Müller

Jacobson

2011

Biochimica et Biophysica Acta (BBA) - Biomembranes

393

461

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Medicinal chemical approaches have been applied to all four of the adenosine receptor (AR) subtypes (A1, A2A, A2B, and A3) to create selective agonists and antagonists for each. The most recent class of selective AR ligands to be reported is the class of A2BAR agonists. The availability of these selective ligands has facilitated research on therapeutic applications of modulating the ARs and in some cases has provided clinical candidates. Prodrug approaches have been developed which improve the bioavailability of the drugs, reduce side-effects, and/or may lead to site-selective effects. The A2A agonist regadenoson (Lexiscan®), a diagnostic drug for myocardial perfusion imaging, is the first selective AR agonist to be approved. Other selective agonists and antagonists are or were undergoing clinical trials for a broad range of indications, including capadenoson and tecadenoson (A1 agonists) for atrial fibrillation, or paroxysmal supraventricular tachycardia, respectively, apadenoson and binodenoson (A2A agonists) for myocardial perfusion imaging, preladenant (A2A antagonist) for the treatment of Parkinson’s disease, and CF101 and CF102 (A3 agonists) for inflammatory diseases and cancer, respectively. This article is part of a Special Issue entitled: “Adenosine Receptors”.

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Section: Adenosine Receptor Agonistsmentioning

confidence: 99%

Recent developments in adenosine receptor ligands and their potential as novel drugs

Müller

Jacobson

2011

Biochimica et Biophysica Acta (BBA) - Biomembranes

393

461

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“…Several review articles on adenosine receptor ligands in general (Müller & Jacobson, 2011a; Müller & Jacobson, 2011b; Fredholm et al, 2011) and A 2A R antagonists in particular (Müller & Ferré, 2010; Clementina & Giuseppe, 2010; Shah & Hodgson, 2010; Cristalli et al, 2009) have appeared recently. The first adenosine receptor antagonists described in the literature were the plant alkaloids caffeine ( 1 ) and theophylline ( 2 ), which are characterized by their core xanthine structure (Figure 1).…”

Section: Overview Of Important A2ar Antagonistsmentioning

confidence: 99%

Past, present and future of A2A adenosine receptor antagonists in the therapy of Parkinson's disease

Armentero

Pinna

Ferré

et al. 2011

Pharmacology & Therapeutics

173

152

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Several selective antagonists for adenosine A2A receptors (A2AR) are currently under evaluation in clinical trials (phases I to III) to treat Parkinson’s disease, and they will probably soon reach the market. The usefulness of these antagonists has been deduced from studies demonstrating functional interactions between dopamine D2 and adenosine A2A receptors in the basal ganglia. At present it is believed that A2AR antagonists can be used in combination with the dopamine precursor L-DOPA to minimize the motor symptoms of Parkinson’s patients. However, a considerable body of data indicates that in addition to ameliorating motor symptoms, adenosine A2AR antagonists may also prevent neurodegeneration. Despite these promising indications, one further issue must be considered in order to develop fully optimized anti-parkinsonian drug therapy, namely the existence of receptor (hetero)dimers/oligomers of G protein-coupled receptors, a topic currently the focus of intense debate within the scientific community. Dopamine D2 receptors (D2Rs) expressed in the striatum are known to form heteromers with A2A adenosine receptors. Thus, the development of heteromer-specific A2A receptor antagonists represents a promising strategy for the identification of more selective and safer drugs.

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“…Recently, A 2A AR agonists have been approved for clinical trials based on their anti-inflammatory and wound-healing properties [15], [28], [29]. In clinical evaluation, the chronic A 2A AR activation was able to reduce the inflammatory status in specific diseases as diabetic nephropathy and to promote healing of diabetic foot ulcers [30].…”

Section: Introductionmentioning

confidence: 99%

A2A Adenosine Receptors Are Differentially Modulated by Pharmacological Treatments in Rheumatoid Arthritis Patients and Their Stimulation Ameliorates Adjuvant-Induced Arthritis in Rats

et al. 2013

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A2A adenosine receptors (ARs) play a key role in the inhibition of the inflammatory process. The purpose of this study was to evaluate the modulation of A2AARs in rheumatoid arthritis (RA) patients after different pharmacological treatments and to investigate the effect of A2AAR stimulation in a rat model of arthritis. We investigated A2AAR density and functionality in RA progression by using a longitudinal study in RA patients before and after methotrexate (MTX), anti-TNFα agents or rituximab treatments. A2AARs were analyzed by saturation binding assays in lymphocytes from RA patients throughout the 24-month study timeframe. In an adjuvant-induced arthritis model in rats we showed the efficacy of the A2AAR agonist, CGS 21680 in comparison with standard therapies by means of paw volume assessment, radiographic and ultrasonographic imaging. Arthritic-associated pain was investigated in mechanical allodynia and thermal hyperalgesia tests. IL-10 release following A2AAR stimulation in lymphocytes from RA patients and in serum from arthritic rats was measured. In lymphocytes obtained from RA patients, the A2AAR up-regulation was gradually reduced in function of the treatment time and the stimulation of these receptors mediated a significant increase of IL-10 production. In the same cells, CGS 21680 did not affected cell viability and did not produced cytotoxic effects. The A2AAR agonist CGS 21680 was highly effective, as suggested by the marked reduction of clinical signs, in rat adjuvant-induced arthritis and associated pain. This study highlighted that A2AAR agonists represent a physiological-like therapeutic alternative for RA treatment as suggested by the anti-inflammatory role of A2AARs in lymphocytes from RA patients. The effectiveness of A2AAR stimulation in a rat model of arthritis supported the role of A2AAR agonists as potential pharmacological treatment for RA.

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A2A Receptor Ligands: Past, Present and Future Trends

Cited by 23 publications

References 138 publications

Recent developments in adenosine receptor ligands and their potential as novel drugs

Recent developments in adenosine receptor ligands and their potential as novel drugs

Past, present and future of A2A adenosine receptor antagonists in the therapy of Parkinson's disease

A2A Adenosine Receptors Are Differentially Modulated by Pharmacological Treatments in Rheumatoid Arthritis Patients and Their Stimulation Ameliorates Adjuvant-Induced Arthritis in Rats

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