Selective attenuation by N-0861 (N6-endonorboran-2-yl-9-methyladenine) of cardiac A1 adenosine receptor-mediated effects in humans

Background: To determine the Adenosine Receptor subtype selectivity of the novel antagonist N-0861, the A1 and A2 receptor-mediated cardiac effects of Adenosine were investigated in 13 patients during continuous intravenous infusion and boluses of Adenosine before and after intravenous infusion of N-0861.

Methods and results: Measurements of the the atria-to-His (A-H) interval, chest Pain severity, and coronary blood flow velocity were made before and after low-dose (69 microg x kg(-1) x min(-1)) intravenous infusion and bolus (2.5 mg) Adenosine. Two doses of N-0861 were infused intravenously, and the Adenosine protocol was repeated. N-0861 0.25 mg/kg abolished the negative dromotropic effect (A-H interval prolongation) and chest discomfort experienced during infusion of Adenosine and attenuated discomfort observed during the boluses of adenosine; however, the increase in coronary blood flow velocity was not significantly affected.

Conclusions: These actions of N-0861 support the concept that the negative dromotropic effect and anginalike Pain caused by Adenosine are A1 Adenosine receptor-mediated, whereas the increase in coronary blood flow velocity is due to activation of A2 Adenosine receptors. N-0861 appears to be an effective and selective A1 Adenosine Receptor antagonist in humans.