Effect of N-0861, a selective adenosine A1 receptor antagonist, on pharmacologic stress imaging with adenosine

N6-endonorboman-2-yl-9-methyladenine (N-0861) is a drug which inhibits the A1 Adenosine Receptor subtype. One proposed use for N-0861 is to eliminate A1 receptor-mediated side effects such as A-V heart block and possibly angina in patients undergoing pharmacologic stress with adenosine. The goal of this study was to determine whether N-0861 has any crossover effect on the A2 vasodilatory action of adenosine or on 201TI uptake which would adversely affect imaging of coronary stenoses.

Methods: In eight dogs with critical left anterior descending (LAD) stenoses, we compared the hemodynamic response to intravenous adenosine (250 micrograms/kg/min) before and after N-0861 administration. LAD and left circumflex (LCx) coronary flows were measured ultrasonically and regional blood flow was assessed using microspheres. Thallium-201 (18.5-37.0 MBq) was injected during adenosine hyperemia while N-0861 was present. Imaging of heart slices was performed and defect magnitude was calculated as LAD:LCx count ratios from regions of interest (ROIs) on images. Regional 201Tl activity and microsphere flow were determined by gamma well counting.

Results: There was no change in mean heart rate, arterial and left atrial pressures, +dP/dt, and ultrasonically measured LAD and LCx coronary flows upon N-0861 administration. In addition, adenosine evoked a similar hemodynamic response after N-0861. There was also no change in coronary flow in the critically stenotic LAD but LCx flow tripled to 106 +/- 14 ml/min (p < 0.01).

Conclusion: These data indicate that N-0861 pretreatment does not adversely affect adenosine A2 receptor-mediated vasodilation and has no effect on the detection of a critical coronary stenosis by 201Tl imaging. Thus, the pretreatment strategy may prove useful for the elimination of A1 receptor-mediated side effects during pharmacologic stress imaging with adenosine.