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

Abstract

UNLABELLED:

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.

• Authors: D K Glover, M Ruiz, V Sansoy, R J Barrett, G A Beller
• Journal: Journal of nuclear medicine : official publication, Society of Nuclear Medicine (J Nucl Med) Vol. 36 Issue 2 Pg. 270-5 (Feb 1995) ISSN: 0161-5505 [Print] United States
• PMID: 7830130 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Norbornanes
• Purinergic P1 Receptor Antagonists
• Thallium Radioisotopes
• N 0861
• Adenine
• Adenosine

Topics

• Adenine (analogs & derivatives, pharmacology)
• Adenosine (antagonists & inhibitors, pharmacology)
• Animals
• Coronary Circulation (drug effects)
• Coronary Disease (diagnostic imaging, physiopathology)
• Dogs
• Exercise Test
• Hemodynamics (drug effects)
• Norbornanes (pharmacology)
• Purinergic P1 Receptor Antagonists
• Radionuclide Imaging
• Thallium Radioisotopes
• Vasodilation (drug effects)