Adenosine is an endogenous
nucleoside that has potent antiarrhythmic effects on
paroxysmal supraventricular tachycardia (PSVT) due to its negative dromotropic effects on the atrioventricular node. In addition to its electrophysiologic effects,
adenosine has important effects on vascular smooth muscle cells, inflammatory cells, the central nervous system, and the kidney. Four known
adenosine receptor subtypes (A1, A2A, A2B, and A3) mediate the pleiotropic effects of
adenosine in humans. These receptors are coupled to a wide range of second messenger cascades. Activation of the A1
adenosine receptor accounts for the negative chronotropic and dromotropic effects of
adenosine, whereas A2A, A2B and A3
adenosine receptor activation are responsible for such effects as coronary vasodilation,
bronchospasm, inhibition of platelet aggregation, and neuronal stimulation. Elucidation of the specific properties of each of the
adenosine receptor subtypes has led to the development of selective
ligands as potential therapeutic agents.
CVT-510, N-(3(R)-tetrahydrofuranyl)-6-aminopurine riboside, was developed as a selective A1
adenosine receptor agonist that specifically targets the atrioventricular node for termination of PSVT. Preliminary clinical trials have shown that
CVT-510 is effective in terminating PSVT and eliminating many of the undesirable adverse effects of
adenosine.
CVT-510 is also being explored as a potential agent for controlling the ventricular rate of
atrial fibrillation and flutter.