Disease relevance of Tecadenoson

• OBJECTIVES: The aim of this study was to evaluate tecadenoson safety and efficacy during conversion of paroxysmal supraventricular tachycardia (PSVT) to sinus rhythm [1].
• CONCLUSIONS: In this study, tecadenoson rapidly terminated sustained PSVT by depressing AV nodal conduction without causing hypotension [1].
• METHODS: In this open-label, multicenter, dose escalation study, tecadenoson was administered to 37 patients (AV node re-entrant tachycardia, n = 29; AV re-entrant tachycardia, n = 8) with inducible PSVT sustained for > or =1 min during an electrophysiology study [1].
• Our objective was to determine whether the antilipolytic effect of N-[3-(R)-tetrahydrofuranyl]-6-aminopurine riboside (CVT-510), an A(1) agonist, could be distinguished from its bradycardia effect and demonstrated in rats with normal or elevated serum NEFA [2].
• At doses of 15 and 30 microg/kg, CVT-510 produced transient second/third degree AV heart block in all four patients treated [3].

High impact information on Tecadenoson

• Termination of paroxysmal supraventricular tachycardia by tecadenoson (CVT-510), a novel A1-adenosine receptor agonist [1].
• Unlike adenosine, which non-selectively activates all four Ado R subtypes and produces unwanted effects, tecadenoson appears to terminate AV node-dependent supraventricular tachycardias without hypotension and bronchoconstriction [1].
• BACKGROUND: Tecadenoson (CVT-510), a novel adenosine receptor (Ado R) agonist, selectively activates the A1 Ado R and prolongs atrioventricular (AV) nodal conduction at doses lower than those required to cause A2 Ado R-mediated coronary and peripheral vasodilation [1].
• To mimic the antilipolytic effect of CVT-510 in awake rats, hearts were perfused with palmitate at concentrations similar to those observed in the in vivo studies (0.8 and 0.2 mM), which decreased myocardial oxygen consumption (MVO(2)) by 11% [2].
• Thus, CVT-510 at doses > or =5-fold lower than those that slow heart rate caused a marked and sustained lowering of normal or elevated NEFA, that when mimicked in vitro decreased MVO(2) and would be expected to improve cardiac efficiency [2].

Biological context of Tecadenoson

• CVT-510 shortened atrial (EC50 = 73 nM) but not the ventricular monophasic action potentials (MAP) [4].
• CONCLUSIONS: CVT-510 promptly prolongs AV nodal conduction and does not affect sinus rate or blood pressure [3].
• A1 selective ligands acting as full agonists (CVT-510) or partial agonists (CVT-2759), antagonists (BG9719/CVT-124) and allosteric enhancers (PD81723) are now under preclinical scrutiny or are being developed for the clinical application in a variety of cardiovascular disorders and will be discussed herein [5].

Anatomical context of Tecadenoson

• Because CVT-510 did not affect the ventricular action potential, it is unlikely that this agonist will have a proarrythmic action in ventricular myocardium [4].

Gene context of Tecadenoson

• CVT-510, the lead compound from a series of selective adenosine A1 receptor agonists, is being developed by CV Therapeutics for the potential treatment of supraventricular tachycardias and atrial arrhythmias [224364], [299365] [6].

Analytical, diagnostic and therapeutic context of Tecadenoson

• 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 [7].

References