Antiarrhythmic - tecadonoson
Cardiac arrhythmias are both a symptom and a cause of various forms of heart disease. The naturally occurring nucleoside adenosine is clinically effective as an antiarrhythmic agent, but its action is very non-specific, acting at all four sub-types of adenosine cell surface receptors (AdoRs), and hence its use all too often leads to unwanted effects such as hypotension. So a more specific agent would, potentially, have significant clinical benefits over adenosine.
The A1 AdoR has a range of cardioprotective functions, such as improving post-ischaemic function, reducing infarct size and giving decreases in arrhythmias, and US company CV Therapeutics is investigating the A1 AdoR agonist tecadenoson as a potential antiarrhythmic agent. Several Phase I trials have been carried out.
In one open label multicentre study, 32 fit volunteers were given tecadenosan as an intravenous bolus in doses ranging from 0.3 to 30µg/kg. It caused dose dependent increases in the A-H intervals of the heart beat, prolonging atrioventricular nodal conduction without affecting sinus rate at the lower doses.1
An open label dose escalation study was carried out in 30 patients with inducible, sustained supraventricular tachycardia. Boluses of between 3 and 15 µg/kg were administered, and after one bolus, supraventricular tachycardias were converted to sinus rhythm in 25 patients in less than a minute, and after a second dose in a further three. It was well tolerated with no adverse events reported, and the trial indicates that it may be of use in controlling the ventricular rate in atrial fibrillation.2
Comparing patients in the study whose arrhythmias were converted to sinus rhythm after receiving tecadenoson with patients similarly converted after receiving adenosine, showed that those receiving the new active had fewer arrhythmias or ventricular ectopic beats. It therefore appears to be less proarrhythmic than adenosine.3
Tecadenoson is undergoing Phase II/III trials as a drug to treat atrial fibrillation and flutter, and in converting patients with paroxysmal supraventricular tachycardias to normal sinus rhythm.