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.


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.
Bertolet
B D
BD
Department of Medicine, University of Florida Health Sciences Center, Gainesville, 32610-0277, USA.
Belardinelli
L
L
Franco
E A
EA
Nichols
W W
WW
Kerensky
R A
RA
Hill
J A
JA
D000225:Adenine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000241:Adenosine / Q000494:pharmacology; D000368:Aged; D003326:Coronary Circulation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D006321:Heart / Q000187:drug effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009636:Norbornanes / Q000494:pharmacology*; D010146:Pain / Q000209:etiology; D058915:Purinergic P1 Receptor Antagonists; D018047:Receptors, Purinergic P1 / Q000502:physiology
D009636:Norbornanes; D058915:Purinergic P1 Receptor Antagonists; D018047:Receptors, Purinergic P1; C073387:N 0861; D000225:Adenine; D000241:Adenosine