Defination

Adenosine is a natural nucleotide, which is the intermediate product of metabolism, chemically 6-amino-9-beta-D-ribofuranosyl-9-H-purine. Adenosine is one of the important active components in the body, helps in cellular energy transfer by forming molecules like adenosine triphosphate (ATP) and adenosine diphosphate (ADP). It also plays a role in signaling various pathways and functions in the body by forming signally molecules like cyclic adenosine monophosphate (cAMP).

In the body

▼▲ Adenosine in the body Function Brain Promoting sleep and suppresses arousal acting as a central nervous system depressant. Heart Causing dilation of the coronary blood vessels that Improving blood circulation to the heart; Increasing the diameter of blood vessels in the peripheral organs; Decreasing heart rate Blood Broken down by adenosine deaminase. By taking medicine like Dipyridamole(inhibitor of adenosine deaminase), it can improve blood flow through the coronary blood vessels that supply the heart muscles. Kidneys, lungs and liver In the kidneys adenosine decreases renal blood flow and decrease the production of rennin from the kidneys. In the lungs it causes constriction of airways and in the liver it leads to constriction of blood vessels and increases breakdown of glycogen to form glucose.

Medical uses

Adenosine has a role in the expansion of coronary artery and myocardial contractility, is clinically applied in the treatment of angina, hypertension, cerebrovascular disorders, stroke sequelae, muscular atrophy, etc. It is also given intravenously (by IV) for treating supraventricular tachycardia and Tl myocardial imaging. It is also used for cardiac stress tests. ? Side effects: Since the half-life of Adenosine is less than 10 seconds, its side effects are usually transient. However, side effects are common, and include flushing, headache, chest discomfort, bronchoconstriction, and occasionally hypotension. Hepatic and renal failure and other drugs except dipyridamole seem to have little effect on the action of adenosine. ? ? Adenosine dose

Mechanism of action

Its function is realized through the activation of the adenosine receptor (A receptor). Adenosine activates G protein coupled potassium channels by binding to the A receptor which makes increasing the outflow of K+ and cell membrane hyperpolarization so as to decrease the automaticity in the atrium, sinoatrial node and atrioventricular node. It can also significantly increase the level of cGMP , prolong ERP of the atrioventricular node and slowing of atrioventricular, depress sympathetic nervous or early and delayed after depolarization induced by isoproterenol and then plays an effective role in arrhythmia. This product has not been classified in I~IV anti arrhythmia medicine. Adenosine receptor A1 receptors, which are found in cardiomyocytes and which are responsible for the inhibition of adenylyl cylase activity which lowers cyclic adenosine monophosphate (AMP) results in sinus slowing, increase in AV node conduction delay, and antagonism of the effects of catecholamines; A2 receptors, which are found in endothelial cells and vascular smooth muscle and are responsible for the enhancement of adenylyl cylase activity and increased cyclic AMP which relaxes smooth muscle. Both negative chronotropic and dromotropic effects of adenosine are cyclic AMP independent (direct action) as well cyclic AMP dependent (indirect action).

Biological Activity

Neurotransmitter that acts as the preferred endogenous agonist at all adenosine receptor subtypes.

Biochem/physiol Actions

Endogenous neurotransmitter at adenosine receptors. Cardioprotective effects may relate to activation of A1 adenosine receptors. The antiplatelet and anti?inflammatory actions of adenosine appear to be mediated via the A2 adenosine receptor. In contrast, adenosine appears to be a pro-inflammatory mediator in asthma and chronic obstructive pulmonary disease (COPD).

Side effects

Adverse reactions to the administration of adenosine are fairly common; however, the short half-life of the drug limits the duration of such events.The most common adverse effects are flushing, chest pain, and dyspnea. Adenosine may induce profound bronchospasm in patients with known reactive airway disease. The mechanism for bronchospasm is unclear, and the effect may last for up to 30 minutes despite the short half-life of the drug.

Drug interactions

Metabolism of adenosine is slowed by dipyridamole, indicating that in patients stabilized on dipyridamole the therapeutically effective dose of adenosine may have to be increased. Methylxanthines antagonize the effects of adenosine via blockade of the adenosine receptors.

Metabolism

It is impossible to study adenosine in classical pharmacokinetic studies, since it is present in various forms in all the cells of the body. An efficient salvage and recycling system exists in the body, primarily in erythrocytes and blood vessel endothelial cells. The halflife in vitro is estimated to be less than 10 seconds, and may be even shorter in vivo.

Purification Methods

Crystallise adenosine from distilled water and dry it at 110o. It has been purified via the picrate, where ethanolic picric acid is added to adenosine and the picrate is filtered off and recrystallised from EtOH. It has m 180-185o(dec). Adenosine is recovered by dissolving 0.4g of the picrate in 80mL of hot H2O, treated with a small quantity of Dowex 1 anion exchange resin in the chloride form, and the resin is filtered off. The filtrate is treated with more resin and filtered again. One equivalent of aqueous NaOH is added to the colourless filtrate which is evaporated to 4mL and cooled to give 0.176g of adenosine m 236o. [Davoll et al. J Chem Soc 967 1948, Davoll & Lowy J Am Chem Soc 73 1650 1951, Beilstein 26 III/IV 3598.]

Precautions

Patients with second- or third-degree A-V block should not receive adenosine. As indicated previously, the use of adenosine in asthmatic patients may exacerbate the asthmatic symptoms.

Ubiquitous Signalling Molecule

Adenosine is a purine nucleoside signaling molecule found ubiquitously in human systems. It plays various roles related to metabolism, regulation of sleep patterns, development, neuroprotection, and cellular homeostasis.

Interaction with Adenosine Receptors

Adenosine interacts with four G protein-coupled receptor (GPCR) subtypes known as A1, A2A, A2B, and A3 adenosine receptors (ARs).
Each receptor subtype has a unique pharmacological profile and tissue distribution, allowing adenosine to modulate diverse physiological processes.

Modulation of Inflammation

Adenosine is a potent modulator of inflammation, making the adenosinergic system a promising pharmacological target for diseases involving inflammation. It regulates immune responses and inflammatory processes in conditions such as rheumatic diseases, neurological disorders, and cancer.

Endogenous Anticonvulsant and Neuroprotectant

Adenosine acts as an endogenous anticonvulsant and neuroprotectant in the brain.
Seizure activity leads to the production of large quantities of adenosine, which helps to stop seizures.

Role in Immune Response

Adenosine serves as a key mediator of the immune response, influencing the activation of immune cells and the generation of reactive oxygen species (ROS). It regulates neutrophil activation, which plays a crucial role in inflammation and immune responses.

Neuromodulatory Function

In the central nervous system (CNS), adenosine acts as a neuromodulation.
Increased extracellular adenosine concentration in response to neuronal stress and damage can promote or attenuate neuroinflammation.

Production and Metabolism

Adenosine is produced through various mechanisms, including the dephosphorylation of adenine nucleotides (ATP, ADP, and AMP) and the release of adenine nucleotides into the extracellular space.
Enzymes like ectonucleoside triphosphate diphosphohydrolase (CD39) and ecto-5鈥?-nucleotidase (CD73) catalyze the conversion of adenine nucleotides to adenosine.

Definition

ChEBI: A ribonucleoside composed of a molecule of adenine attached to a ribofuranose moiety via a beta1N9-glycosidic bond.

Brand name

Adenocard (Astellas); Adenoscan (Astellas).

General Description

Adenosine is a purine nucleoside and a building block of RNA and many other biomolecules such as adenosine triphosphate and nicotinamide adenine dinucleotide. In the extracellular space, ecto-5′-nucleotidase (CD73) dephosphorylates adenosine triphosphate (ATP) to produce adenosine. Adenosine has four receptors namely A1R, A2AR A2BR and A3R. Adenosine plays a key role in the osteogenic differentiation. A1R induces osteoclast differentiation and A2AR induces osteoblast differentiation.