Disease relevance of N-0861

• Pertussis toxin pretreatment and/or the selective A1-adenosine receptor antagonists 1,3-dipropyl-8-cyclopentylxanthine (DPCPX) and (+/-)N6-endonorbornan-2-yl-9-methyladenine (N-0861) were used to prevent activation of A1-adenosine receptors in these cells [1].
• OBJECTIVE: To study antagonism of A1 adenosine receptors in an anaesthetised open chest swine model, the selective A1 receptor antagonist, N6-endonorbornan-2-yl-9-methyladenine (N-0861), was examined to see if it attenuates bradycardia, augments reflex tachycardia associated with adenosine infusion, or both [2].
• Left ventricular dP/dt and rate-pressure product were maintained with N-0861 and adenosine, and N-0861 unmasked a postadenosine reflex tachycardia [2].
• RESULTS: N-0861 significantly enhanced immediate postdefibrillation electrophysiological and haemodynamic recovery compared to placebo for ventricular fibrillation episodes lasting 35 s [3].
• 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 [4].

High impact information on N-0861

• 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 [5].
• The results indicate that both N-0861 and WRC-0342 are neutral antagonists, whereas both CPX and WRC-0571 are antagonists with inverse agonist activity [6].
• Adenosine A1-receptor occupancy predicts A1-receptor antagonist effects of N-0861 [7].
• Thallium-201 (18.5-37.0 MBq) was injected during adenosine hyperemia while N-0861 was present [4].
• Effect of N-0861, a selective adenosine A1 receptor antagonist, on pharmacologic stress imaging with adenosine [4].

Biological context of N-0861

• At 60 s postdefibrillation, when other variables were equal, the first derivative of left ventricular pressure in the presence of N-0861 remained 26% greater than placebo [3].
• 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 [4].
• N-0861 alone had only a modest effect on renal or systemic hemodynamics, but produced significant dose-related diuresis/natriuresis [8].
• The selectivity of antagonism of A1 vs. A2 receptors by N-0861 was evaluated by generating dose-response curves to adenosine-induced bradycardia (A1 effect), and vasodilation in the in situ constant-flow perfused rat hindquarter vasculature (A2 effect) [9].

Anatomical context of N-0861

• However, in the left atrium, N-0861 (pKB = 6.2) and DPCPX (pKB = 8.9) were no more potent in antagonizing responses to the A1-selective agonists than they were in antagonizing responses to NECA.(ABSTRACT TRUNCATED AT 250 WORDS)[10]
• Receptor binding studies indicated that N-0861 competitively displaced the binding of 8-cyclopentyl-1,3-[3H]dipropylxanthine to crude guinea pig and human atrial membranes (Ki values of 0.62 and 0.7 microM, respectively) but did not displace the binding of S-(p-nitro[3H]benzyl)-6-thioinosine [11].
• N-0861 significantly reduced stimulus to His bundle prolongation induced by either hypoxia or reduced perfusion ("ischemia") but did not attenuate the hypoxia-induced decrease in coronary perfusion pressure [11].

Associations of N-0861 with other chemical compounds

• The selective A1-adenosine receptor antagonist N-0861 (9-methyladenine derivative) antagonized the effects of adenosine on afterdepolarizations, ITi, and TA [12].

Analytical, diagnostic and therapeutic context of N-0861

• Plasma concentrations of N-0861 were determined with an HPLC method [7].

References