Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0016382 (flushing)
 6,387 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Tecadenoson is a novel selective A1 adenosine receptor agonist that is currently being evaluated for the conversion of paroxysmal supraventricular tachycardia (PSVT) to sinus rhythm. By selectively targeting the A1 receptor, tecadenoson may be associated with fewer adverse effects such as flushing, dyspnea, chest discomfort, and hypotension than adenosine, which is a nonselective agonist of all 4 adenosine receptors. Based on the results of phase I and phase II clinical trials, tecadenoson appears to be an effective agent for producing rapid and sustained conversion of PSVT to sinus rhythm. Additionally, the adverse effects that are typically attributed to adenosine's nonselective stimulation of the A2A, A2B, and A3 receptors appear to occur less frequently with the use of tecadenoson. Tecadenoson also appears to be associated with a lower incidence of atrial fibrillation following conversion of PSVT compared with the rates that have been associated with adenosine in the literature. A randomized, prospective trial will need to be conducted in the future to appropriately compare the safety and efficacy of tecadenoson and adenosine.
 ...
PMID:Tecadenoson: a novel, selective A1 adenosine receptor agonist. 1623 Aug 91

Adenosine is a ubiquitous, endogenous purine involved in a variety of physiological and pathophysiological regulatory mechanisms. Adenosine has been proposed as an endogenous antiarrhythmic substance to prevent hypoxia/ischemia-induced arrhythmias. Adenosine (and its precursor, ATP) has been used in the therapy of various cardiac arrhythmias over the past six decades. Its primary indication is treatment of paroxysmal supraventricular tachycardia, but it can be effective in other forms of supraventricular and ventricular arrhythmias, like sinus node reentry based tachycardia, triggered atrial tachycardia, atrioventricular nodal reentry tachycardia, or ventricular tachycardia based on a cAMP-mediated triggered activity. The main advantage is the rapid onset and the short half life (1- 10 sec). Adenosine exerts its antiarrhythmic actions by activation of A1 adenosine receptors located in the sinoatrial and atrioventricular nodes, as well as in activated ventricular myocardium. However, adenosine can also elicit A2A, A2B and A3 adenosine receptor-mediated global side reactions (flushing, dyspnea, chest discomfort), but it may display also proarrhythmic actions mediated by primarily A1 adenosine receptors (e.g. bradyarrhythmia or atrial fibrillation). To avoid the non-specific global adverse reactions, A1 adenosine receptor- selective full agonists (tecadenoson, selodenoson, trabodenoson) have been developed, which agents are currently under clinical trial. During long-term administration with orthosteric agonists, adenosine receptors can be internalized and desensitized. To avoid desensitization, proarrhythmic actions, or global adverse reactions, partial A1 adenosine receptor agonists, like CVT-2759, were developed. In addition, the pharmacologically "silent" site- and event specific adenosinergic drugs, such as adenosine regulating agents and allosteric modulators, might provide attractive opportunity to increase the effectiveness of beneficial actions of adenosine and avoid the adverse reactions.
...
PMID:The Janus face of adenosine: antiarrhythmic and proarrhythmic actions. 2535 87