A<sub>1</sub>adenosine receptor agonists and their potential therapeutic applications

Elzein, Elfatih; Zablocki, Jeff

doi:10.1517/13543780802497284

Cited by 81 publications

(75 citation statements)

References 55 publications

(54 reference statements)

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“…However, it was shown later that adenosine infusion provoked oscillation of chest pain without involvement of opioids [807]. Yet, A1R agonists were recommended for the treatment of neuropathic pain as well as cardioprotective agents [808].…”

Section: Anginamentioning

confidence: 99%

Cardiac purinergic signalling in health and disease

Burnstock

Pelleg

2014

Purinergic Signalling

118

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This review is a historical account about purinergic signalling in the heart, for readers to see how ideas and understanding have changed as new experimental results were published. Initially, the focus is on the nervous control of the heart by ATP as a cotransmitter in sympathetic, parasympathetic, and sensory nerves, as well as in intracardiac neurons. Control of the heart by centers in the brain and vagal cardiovascular reflexes involving purines are also discussed. The actions of adenine nucleotides and nucleosides on cardiomyocytes, atrioventricular and sinoatrial nodes, cardiac fibroblasts, and coronary blood vessels are described. Cardiac release and degradation of ATP are also described. Finally, the involvement of purinergic signalling and its therapeutic potential in cardiac pathophysiology is reviewed, including acute and chronic heart failure, ischemia, infarction, arrhythmias, cardiomyopathy, syncope, hypertrophy, coronary artery disease, angina, diabetic cardiomyopathy, as well as heart transplantation and coronary bypass grafts.

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Section: Anginamentioning

confidence: 99%

Cardiac purinergic signalling in health and disease

Burnstock

Pelleg

2014

Purinergic Signalling

118

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“…Some, such as tecadenoson, selodenoson, and PJ-875, are being developed for the treatment of supraventricular tachyarrhythmias. 29,30 Theoretically, these drugs may have several advantages over adenosine, including more sustained and selective cardiac A1 receptor effect and fewer adverse effects (eg, hypotension, flushing, bronchoconstriction, chest discomfort) in the assessment of PVs at risk of reconnection after PVI.…”

Section: Novelty and Potential Clinical Relevancementioning

confidence: 99%

Mechanisms by Which Adenosine Restores Conduction in Dormant Canine Pulmonary Veins

et al. 2010

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Background-Adenosine acutely reconnects pulmonary veins (PVs) after radiofrequency application, revealing "dormant conduction" and identifying PVs at risk of reconnection, but the underlying mechanisms are unknown. Methods and Results-Canine PV and left-atrial (LA) action potentials were recorded with standard microelectrodes and ionic currents with whole-cell patch clamp before and after adenosine perfusion. PVs were isolated with radiofrequency current application in coronary-perfused LA-PV preparations. Adenosine abbreviated action potential duration similarly in PV and LA but significantly hyperpolarized resting potential (by 3.9Ϯ0.5%; PϽ0.05) and increased dV/dt max (by 34Ϯ10%) only in PV. Increased dV/dt max was not due to direct effects on I Na , which was reduced similarly by adenosine in LA and PV but correlated with resting-potential hyperpolarization (rϭ0.80). Adenosine induced larger inward rectifier K ϩ current (I KAdo ) in PV (eg, -2.28Ϯ0.04 pA/pF; -100 mV) versus LA (-1.28Ϯ0.16 pA/pF). Radiofrequency ablation isolated PVs by depolarizing resting potential to voltages positive to -60 mV. Adenosine restored conduction in 5 dormant PVs, which had significantly more negative resting potentials (-57Ϯ6 mV) versus nondormant (-46Ϯ5 mV, nϭ6; PϽ0.001) before adenosine. Adenosine hyperpolarized both, but more negative resting-potential values after adenosine in dormant PVs (-66Ϯ6 mV versus -56Ϯ6 mV in nondormant; PϽ0.001) were sufficient to restore excitability. Adenosine effects on resting potential and conduction reversed on washout. Spontaneous recovery of conduction occurring in dormant PVs after 30 to 60 minutes was predicted by the adenosine response. Key Words: arrhythmia ablation Ⅲ adenosine Ⅲ atrium Ⅲ conduction Ⅲ electrophysiology Ⅲ ion channels P ulmonary vein isolation (PVI) is an effective treatment for atrial fibrillation (AF). 1,2 Nevertheless, many patients require repeated ablation procedures because of AF recurrence, which in most cases are associated with reconnection of previously isolated PVs. 3,4 It has recently been noted that intravenous purinergic agonists such as adenosine can transiently restore conduction through a previously isolated PV, a phenomenon called "dormant conduction." [5][6][7][8] The demonstration of dormant conduction has predictive value for eventual reconnection, and additional radiofrequency (RF) applications to veins showing dormant conduction at the time of initial PVI may prevent reconnection and AF recurrence. 6 -8 The mechanisms by which adenosine restores conduction to dormant PVs are unknown. The objectives of this study were to (1) explore the effects of adenosine on ionic currents and action potentials (APs) in canine left-atrial (LA) and PV cardiomyocytes, and (2) relate these effects to changes in conduction between the PV and LA after RF ablation in an in vitro model. Conclusions-Adenosine Clinical Perspective on p 972 Materials and MethodsSee the online-only Data Supplement for the complete Materials and Methods section. The following text summarize...

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“…GP-3269, an adenosine kinase inhibitor (Fig. 29.1 ), and GW-493838, an A 1 R agonist, may be useful in the treatment of pain and migraines (Elzein and Zablocki 2008 ;Erion et al 1997 ;Kowaluk and Jarvis 2000 ;McGaraughty et al 2005 ;Wiesner et al 1999 ) (Table 29.2 ). Guanosine was also found to have an antinociceptive effect in mice (Schmidt et al 2009 ) , suggesting that it may also be a potential target for the treatment of pain.…”

Section: Pain Managementmentioning

confidence: 99%

Anatomical Distribution of Nucleoside System in the Human Brain and Implications for Therapy

Kovács

Dobolyi

2012

Adenosine

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Nucleosides have a wide range of physiological and pathophysiological roles in the human brain as modulators of a variety of neural functions. For example, adenosine, inosine, guanosine, and uridine participate in the mechanisms underlying memory, cognition, sleep, pain, depression, schizophrenia, epilepsy, Alzheimer's disease, Huntington's disease, and Parkinson's disease. Consequently, increasing attention is now being given to the speci fi c role of nucleosides in physiological and pathological processes in the human brain. Different elements of nucleoside system, including nucleoside concentrations, metabolic enzyme activity, and expression of nucleoside transporters and receptors, may be changed under normal and pathological conditions. The alterations suggest that interlinked elements of the nucleoside system are functioning in a tightly concerted manner.Nucleoside levels, activity of nucleoside metabolic enzymes, and expression of nucleoside transporters and receptors are unevenly distributed in the brain, suggesting that nucleosides have different roles in functionally distinct human brain areas. The aim of this chapter is to summarize our present knowledge of the anatomical distribution of nucleoside system in the human brain, placing emphasis on potential therapeutic pharmacological strategies.

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A₁adenosine receptor agonists and their potential therapeutic applications

Cited by 81 publications

References 55 publications

Cardiac purinergic signalling in health and disease

Cardiac purinergic signalling in health and disease

Mechanisms by Which Adenosine Restores Conduction in Dormant Canine Pulmonary Veins

Anatomical Distribution of Nucleoside System in the Human Brain and Implications for Therapy

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A1adenosine receptor agonists and their potential therapeutic applications

Cited by 81 publications

References 55 publications

Cardiac purinergic signalling in health and disease

Cardiac purinergic signalling in health and disease

Mechanisms by Which Adenosine Restores Conduction in Dormant Canine Pulmonary Veins

Anatomical Distribution of Nucleoside System in the Human Brain and Implications for Therapy

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A₁adenosine receptor agonists and their potential therapeutic applications