ATPace™: injectable adenosine 5′-triphosphate

Abstract

ATPace™, a novel injectable formulation of adenosine 5′-triphosphate (ATP), is developed by Cordex Pharma, Inc. (Cordex) as a diagnostic and therapeutic drug for the management of cardiac bradyarrhythmias. Extracellular ATP exerts multiple effects in various cell types by activating cell-surface receptors known as P2 receptors. In the heart, ATP suppresses the automaticity of cardiac pacemakers and atrioventricular (AV) nodal conduction via adenosine, the product of its degradation by ecto-enzymes, as well as by triggering a cardiocardiac vagal reflex. ATP, given as a rapid intravenous bolus injection, has been used since the late 1940s as a highly effective and safe therapeutic agent for the acute termination of reentrant paroxysmal supraventricular tachycardia (PSVT) involving the AV node. In addition, preliminary studies have shown that ATP can also be used as a diagnostic agent for the identification of several cardiac disorders including sinus node dysfunction (sick sinus syndrome), dual AV nodal pathways, long QT syndrome, and bradycardic syncope. The US Food and Drug Administration has approved Cordex formulation for ATP as an Investigational New Drug and two pathways for its marketing approval; one therapeutic, i.e., acute termination of paroxysmal PSVT, and the other diagnostic, i.e., the identification of patients with bradycardic syncope who can benefit from pacemaker therapy. The scientific rationale for the development of ATPace™ is discussed.

Discrimination of Ribonucleoside Mono-, Di-, and Triphosphates Using an Engineered Nanopore

“…It is also an adjunct drug for chronic hepatitis, coronary heart disease, nephritis, and cerebral arteriosclerosis. 36 Since ATP is usually synthesized from AMP or adenosine by yeast fermentation in industry, 37,38 AMP and ADP are inevitably introduced as impurities in the ATP production process. 39 Thus, the simultaneous analysis of ribonucleotide impurities is of great importance in the pharmaceutical quality control of ATP drugs.…”

“…As essential nutrients, energy supplies, and coenzyme factors, natural ribonucleotides are widely used in the pharmacy industry. − For example, ATP is an important clinical drug in the treatment of metabolic disorders and muscular atrophy. It is also an adjunct drug for chronic hepatitis, coronary heart disease, nephritis, and cerebral arteriosclerosis .…”

Emergency department visits for paroxysmal supraventricular tachycardia in Saudi Arabia

“…If the arrhythmia was not converted within 1 min, a second bolus of 12 mg was injected as described previously. [ 18 19 20 ]…”

Historical and Current Adenosine Receptor Agonists in Preclinical and Clinical Development

“…Adenosine is considered as an endogenous antiarrhythmic agent partly due to its endogenous anti-ischemic property (Kiesman et al, 2009; Szentmiklosi et al, 2015). As described earlier, infused adenosine (under the name of Adenocard, approved in 1989, Olsson, 2003) and its precursor ATP have long been used for the treatment of paroxysmal supraventricular tachycardia (PSVT) (Pelleg et al, 2012; Szentmiklosi et al, 2015). The antiarrhythmic action of adenosine has been suggested to occur via the A 1 AR in the sinoatrial and atrioventricular nodes, which leads to modification of AV nodal conduction (Kiesman et al, 2009).…”