Termination of paroxysmal supraventricular tachycardia by tecadenoson (CVT-510), a novel A1-adenosine receptor agonist.

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Prystowsky EN, Niazi I, Curtis AB, Wilber DJ, Bahnson T, Ellenbogen K, Dhala A, Bloomfield DM, Gold M, Kadish A, Fogel RI, Gonzalez MD, Belardinelli L, Shreeniwas R, Wolff AA

Termination of paroxysmal supraventricular tachycardia by tecadenoson (CVT-510), a novel A1-adenosine receptor agonist.

J Am Coll Cardiol. 2003 Sep 17;42(6):1098-102.

PubMed ID

13678937 [ View in PubMed

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Abstract

OBJECTIVES: The aim of this study was to evaluate tecadenoson safety and efficacy during conversion of paroxysmal supraventricular tachycardia (PSVT) to sinus rhythm. 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. 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. 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. Seven regimens (0.3 to 15 microg/kg) of up to two identical tecadenoson intravenous bolus doses were administered. RESULTS: After the first or second bolus, PSVT converted to sustained sinus rhythm for > or =5 min in 86.5% (32/37) of the patients, with 91% (29/32) of the conversions occurring after the first bolus (most within 30 s), coincident with anterograde conduction block in the AV node. No effects on sinus cycle length (SCL) or systolic blood pressure were observed. The atrial-His (AH), but not the His-ventricular (HV) interval was prolonged up to 5 min after the final tecadenoson bolus, returning to baseline by 10 min. Tecadenoson was generally well tolerated. CONCLUSIONS: In this study, tecadenoson rapidly terminated sustained PSVT by depressing AV nodal conduction without causing hypotension. After sinus rhythm restoration, there was minimal AH interval prolongation without HV interval or SCL prolongation.

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Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Tecadenoson	Adenosine receptor A1	Protein	Humans	Unknown	Not Available	Details