capadenoson (BAY 684986) / Bayer - LARVOL DELTA

Investigation of adenosine A1 receptor-mediated β-arrestin 2 recruitment using a split-luciferase assay. (PubMed, Front Pharmacol) - "Capadenoson, in contrast to adenosine, CPA, or NECA, shows only partial agonism in this assay with respect to the recruitment of β-arrestin 2, whereas it shows full agonism in the case of the inhibitory effect of AAR on cAMP production... The presented assay is a useful tool for the quantitative study of AAR-mediated β-arrestin 2 recruitment. It allows data collection for stimulatory, inhibitory, and modulatory substances and is also suitable for more complex substance mixtures such as valerian extract."

Journal • Heart Failure • ARRB1

Lack of efficacy of a partial adenosine A1 receptor agonist in neuropathic pain models in mice. (PubMed, Purinergic Signal) - "However, administration of capadenoson at established in vivo doses (0.03-1.0 mg/kg) did not alter mechanical hypersensitivity in the spared nerve injury and paclitaxel models of neuropathic pain, whereas the standard analgesic pregabalin significantly inhibited the pain behavior. Moreover, capadenoson failed to affect potassium currents in DRG neurons, in contrast to a full AR agonist. Despite expression of AR in nociceptive neurons, our data do not support the hypothesis that pharmacological intervention with partial AR agonists might be a valuable approach for the treatment of neuropathic pain."

Journal • Preclinical • Immunology • Neuralgia • Pain • Peripheral Neuropathic Pain

Pharmacological Insights Into Safety and Efficacy Determinants for the Development of Adenosine Receptor Biased Agonists in the Treatment of Heart Failure. (PubMed, Front Pharmacol) - "We compare this agent with the well-characterized, pan-adenosine receptor (AR) agonist NECA, capadenoson, and the AR biased agonist VCP746, previously shown to be safe and cardioprotective in pre-clinical models of heart failure. The failure of neladenoson to reach primary endpoints in clinical trials suggests that AR-mediated cAMP inhibition may be a poor indicator of effectiveness in chronic heart failure. This study provides additional information that can aid future screening and/or design of improved AR agonists that are safe and efficacious in treating heart failure in patients."

Clinical • Journal • Cardiovascular • Congestive Heart Failure • Heart Failure

Design and Pharmacological Profile of a Novel Covalent Partial Agonist for the Adenosine A Receptor. (PubMed, Biochem Pharmacol) - "For the human adenosine A receptor (hAAR) this has led to the discovery of capadenoson, which has been in phase IIa clinical trials for heart failure...These results led us to conclude that LUF7746 is a novel covalent hAAR partial agonist and a valuable chemical probe for further mapping the receptor activation process. It may also serve as a prototype for a therapeutic approach in which a covalent partial agonist may cause less on-target side effects, conferring enhanced safety compared to a full agonist."

Journal • Cardiovascular • Congestive Heart Failure • Heart Failure

Adenosine receptor targeting in health and disease (Expert Opin Investig Drugs) - Selective ligands of A1, A2A, A2B & A3 adenosine receptors are likely to find applications in the treatment of pain, ischemic conditions, glaucoma, asthma, arthritis, cancer & other disorders in which inflammation is a feature; The aim of this review is to provide an overview of the present knowledge regarding the role of these adenosine receptors in health & disease

Expert opinion • Cardiovascular

Probe dependence of allosteric enhancers on the binding affinity of adenosine A -receptor agonists at rat and human A -receptors measured using NanoBRET. (PubMed, Br J Pharmacol) - "These results demonstrate the power of the NanoBRET ligand binding approach to study the effect of allosteric ligands on the binding of fluorescent agonists to the adenosine A -receptor in intact living cells. Furthermore, our studies suggests that VCP171 and PD 81,723 may switch a proportion of A -receptors to an active agonist conformation (R*)."

Journal • Preclinical

The effect of two selective A -receptor agonists and the bitopic ligand VCP746 on heart rate and regional vascular conductance in conscious rats. (PubMed, Br J Pharmacol) - "These results suggest VCP746 mediates its cardiovascular effects via activation of A rather than A adenosine receptors. This has implications for the design of future bitopic ligands that incorporate A allosteric ligand moieties."

Journal • Preclinical