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(Circulation. 1996;93:1871-1876.)
© 1996 American Heart Association, Inc.

Articles

Selective Attenuation by N-0861 (N⁶-Endonorboran-2-yl-9-Methyladenine) of Cardiac A₁ Adenosine Receptor–Mediated Effects in Humans

Barry D. Bertolet, MD; Luiz Belardinelli, MD; Elizabeth A. Franco, RN; Wilmer W. Nichols, PhD; Richard A. Kerensky, MD; James A. Hill, MD

From the Division of Cardiology, Department of Medicine, University of Florida Health Sciences Center, Gainesville.

Correspondence to Barry D. Bertolet, MD, Division of Cardiology, Box 100277, JHMHC, University of Florida, Gainesville, FL 32610-0277.

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 atria-to-His (A-H) interval, chest pain severity, and coronary blood flow velocity were made before and after low-dose (69 µg · kg^-1 · 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.

Key Words: adenosine • electrophysiology • receptors, purinergic • circulation

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