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Journal of Drug Targeting 2015Adenosine is a naturally occurring purine nucleoside in every cell. Many critical treatments such as modulating irregular heartbeat (arrhythmias), regulation of central... (Review)
Review
Adenosine is a naturally occurring purine nucleoside in every cell. Many critical treatments such as modulating irregular heartbeat (arrhythmias), regulation of central nervous system (CNS) activity and inhibiting seizural episodes can be carried out using adenosine. Despite the significant potential therapeutic impact of adenosine and its derivatives, the severe side effects caused by their systemic administration have significantly limited their clinical use. In addition, due to adenosine's extremely short half-life in human blood (<10 s), there is an unmet need for sustained delivery systems to enhance efficacy and reduce side effects. In this article, various adenosine delivery techniques, including encapsulation into biodegradable polymers, cell-based delivery, implantable biomaterials and mechanical-based delivery systems, are critically reviewed and the existing challenges are highlighted.
Topics: Adenosine; Animals; Drug Delivery Systems; Drug Design; Half-Life; Humans; Polymers
PubMed: 26453156
DOI: 10.3109/1061186X.2015.1058803 -
Neurochemical Research Dec 2022Several experimental studies have linked adenosine's neuroprotective role in cerebral ischemia. During ischemia, adenosine is formed due to intracellular ATP breakdown... (Review)
Review
Several experimental studies have linked adenosine's neuroprotective role in cerebral ischemia. During ischemia, adenosine is formed due to intracellular ATP breakdown into ADP, further when phosphate is released from ADP, the adenosine monophosphate is formed. It acts via A1, A2, and A3 receptors found on neurons, blood vessels, glial cells, platelets, and leukocytes. It is related to various effector systems such as adenyl cyclase and membrane ion channels via G-proteins. Pharmacological manipulation of adenosine receptors by agonists (CCPA, ADAC, IB-MECA) increases ischemic brain damage in various in vivo and in vitro models of cerebral ischemia whereas, agonist can also be neuroprotective. Mainly, receptor antagonists (CGS15943, MRS1706) indicated neuroprotection. Later, various studies also revealed that the downregulation or upregulation of specific adenosine receptors is necessary during the recovery of cerebral ischemia by activating several downstream signaling pathways. In the current review, we elaborate on the dual roles of adenosine and its receptor subtypes A1, A2, and A3 and their involvement in the pathobiology of cerebral ischemic injury. Adenosine-based therapies have the potential to improve the outcomes of cerebral injury patients, thereby providing them with a more optimistic future.
Topics: Humans; Adenosine; Receptors, Purinergic P1; Brain Ischemia; Ischemia; Adenosine Diphosphate
PubMed: 36042141
DOI: 10.1007/s11064-022-03737-3 -
Connecticut Medicine Nov 1990
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Life Sciences Oct 2021Adenosine, an endogenous purine nucleoside, is a well-known actor of the immune system and the inflammatory response both in physiologic and pathologic conditions. By... (Review)
Review
Adenosine, an endogenous purine nucleoside, is a well-known actor of the immune system and the inflammatory response both in physiologic and pathologic conditions. By acting upon particular, G-protein coupled adenosine receptors, i.e., A1, A2- a & b, and A3 receptors mediate a variety of intracellular and immunomodulatory actions. Several studies have elucidated Adenosine's effect and its up-and downstream molecules and enzymes on the anti-tumor response against several types of cancers. We have also targeted a couple of molecules to manipulate this pathway and get the immune system's desired response in our previous experiences. Besides, the outgrowth of the studies on ocular Adenosine in recent years has significantly enhanced the knowledge about Adenosine and its role in ocular immunology and the inflammatory response of the eye. Glaucoma is the second leading cause of blindness globally, and the recent application of Adenosine and its derivatives has shown the critical role of the adenosine pathway in its pathophysiology. However, despite a very promising background, the phase III clinical trial of Trabodenoson failed to achieve the non-inferiority goals of the study. In this review, we discuss different aspects of the abovementioned pathway in ophthalmology and ocular immunology; following a brief evaluation of the current immunotherapeutic strategies, we try to elucidate the links between cancer immunotherapy and glaucoma in order to introduce novel therapeutic targets for glaucoma.
Topics: Adenosine; Animals; Eye; Glaucoma; Humans; Immunity; Immunotherapy; Neoplasms
PubMed: 34245774
DOI: 10.1016/j.lfs.2021.119796 -
Current Opinion in Neurobiology Jun 2017Slow wave activity (SWA) during slow wave sleep (SWS) is the best indicator of the sleep homeostasis. The intensity of the SWA observed during SWS that follows prolonged... (Review)
Review
Slow wave activity (SWA) during slow wave sleep (SWS) is the best indicator of the sleep homeostasis. The intensity of the SWA observed during SWS that follows prolonged waking is directly correlated with the duration of prior waking and its intensity decays during SWS suggesting a buildup and a resolution of sleep need. This sleep-homeostasis related SWA results from a buildup and decay of extracellular adenosine that acts at neuronal adenosine A1 receptors to facilitate SWA and is metabolized by adenosine kinase found in glia. This local neuronal-glial circuit for homeostatic SWA is primarily under the requisite control of two genes, the Adora1 and Adk, encoding the responsible adenosine receptor and adenosine's highest affinity metabolizing enzyme.
Topics: Adenosine; Homeostasis; Humans; Neuroglia; Neurons; Sleep
PubMed: 28633050
DOI: 10.1016/j.conb.2017.05.015 -
Ceskoslovenska Fysiologie 2015Adenosine is not just a major component of adenine nucleotides and ribonucleic acids, but also has its own signaling functions. ExtraceIlular level of adenosine in an... (Review)
Review
Adenosine is not just a major component of adenine nucleotides and ribonucleic acids, but also has its own signaling functions. ExtraceIlular level of adenosine in an organism is strictly maintained through the balance between its formation, degradation and transport. Adenosine is formed by enzymatic degradation of adenosine triphosphate and eliminated by phosphorylation to adenosine monophosphate or by deamination to inosine. Transport of adenosine across the cell membrane is ensured by equilibrative and concentrative nucleoside transporters. All these processes participate in maintenance of adenosine level under normal conditions, but a balanced equilibrium can be disrupted in some pathophysiological situations. Extracellular adenosine as a signaling molecule binds to adenosine receptors, which may trigger via their cognate trimeric G proteins different signaling pathways. In this way, adenosine regulates energy homeostasis and affects the function of various organs. Targeted pharmacological manipulations of specific adenosine receptor subtypes or enzymes involved in its metabolism can potentially be used for therapeutic purposes.
Topics: Adenosine; Humans; Nucleoside Transport Proteins; Receptors, Purinergic P1; Signal Transduction
PubMed: 26738245
DOI: No ID Found -
Neuropharmacology May 2013In rodents, insufficient adenosine produces behavioral and physiological symptoms consistent with several comorbidities of autism. In rodents and humans, stimuli... (Review)
Review
In rodents, insufficient adenosine produces behavioral and physiological symptoms consistent with several comorbidities of autism. In rodents and humans, stimuli postulated to increase adenosine can ameliorate these comorbidities. Because adenosine is a broad homeostatic regulator of cell function and nervous system activity, increasing adenosine's influence might be a new therapeutic target for autism with multiple beneficial effects. This article is part of the Special Issue entitled 'Neurodevelopmental Disorders'.
Topics: Adenosine; Animals; Autistic Disorder; Humans
PubMed: 22940000
DOI: 10.1016/j.neuropharm.2012.08.013 -
Der Internist Mar 1995
Review
Topics: Adenosine; Electrocardiography; Heart Conduction System; Humans; Tachycardia, Paroxysmal; Tachycardia, Supraventricular
PubMed: 7737824
DOI: No ID Found -
Clinical and Investigative Medicine.... Oct 1992Adenosine, an endogenous nucleoside has been recently approved for use in the treatment of paroxysmal supraventricular tachycardia. Adenosine is nearly 100% effective in... (Comparative Study)
Comparative Study Review
Adenosine, an endogenous nucleoside has been recently approved for use in the treatment of paroxysmal supraventricular tachycardia. Adenosine is nearly 100% effective in terminating tachycardia in which the atrioventricular node forms part of the reentrant circuit. Although most ventricular tachycardias are insensitive to adenosine, this substance is effective in ventricular tachycardia induced by catecholamines or exercise. An intravenous bolus dose of 6 mg is the initial dose. If no effect is noted a further bolus of 12 mg can be given. The most common side effects are dyspnea, chest pressure and facial flushing. This article reviews, in addition, some of the comparative trials with verapamil and adenosine triphosphate, some of the additional therapeutic indications, the possible mechanisms of action in cardiac tissue, and the type of purinergic receptors involved in the antiarrhythmic effects of adenosine.
Topics: Adenosine; Animals; Heart Conduction System; Humans; Tachycardia, Paroxysmal; Tachycardia, Supraventricular; Vasodilation
PubMed: 1458718
DOI: No ID Found -
International Journal of Molecular... May 2024This review article focuses on the role of adenosine in coronary artery disease (CAD) diagnosis and treatment. Adenosine, an endogenous purine nucleoside, plays crucial... (Review)
Review
This review article focuses on the role of adenosine in coronary artery disease (CAD) diagnosis and treatment. Adenosine, an endogenous purine nucleoside, plays crucial roles in cardiovascular physiology and pathology. Its release and effects, mediated by specific receptors, influence vasomotor function, blood pressure regulation, heart rate, and platelet activity. Adenosine therapeutic effects include treatment of the no-reflow phenomenon and paroxysmal supraventricular tachycardia. The production of adenosine involves complex cellular pathways, with extracellular and intracellular synthesis mechanisms. Adenosine's rapid metabolism underscores its short half-life and physiological turnover. Furthermore, adenosine's involvement in side effects of antiplatelet therapy, particularly ticagrelor and cangrelor, highlights its clinical significance. Moreover, adenosine serves as a valuable tool in CAD diagnosis, aiding stress testing modalities and guiding intracoronary physiological assessments. Its use in assessing epicardial stenosis and microvascular dysfunction is pivotal for treatment decisions. Overall, understanding adenosine's mechanisms and clinical implications is essential for optimizing CAD management strategies, encompassing both therapeutic interventions and diagnostic approaches.
Topics: Humans; Adenosine; Coronary Artery Disease; Animals; Adenosine Monophosphate; Platelet Aggregation Inhibitors
PubMed: 38892037
DOI: 10.3390/ijms25115852