Journal article
Effects of N6-endonorbornan-2-yl-9-methyladenine, N0861, on negative chronotropic and vasodilatory actions of adenosine in the canine heart in vivo
Canadian journal of physiology and pharmacology, v 70(11), pp 1450-1456
01 Nov 1992
PMID: 1296857
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Abstract
The pharmacology of N
6
-endonorbornan-2-yl-9-methyladenine (N0861), a new selective antagonist of adenosine at the A
1
adenosine receptor subtype (A
1
-AdoR), was studied in vivo using a canine model. First, the pharmacokinetics of N0861 were determined in anesthetized dogs. The time-dependent decay of plasma levels of N0861 fitted a two-compartment polyexponential model with α-phase t
1/2
= 3.80 min and β-phase t
1/2
= 80.55 min. Secondly, the effect of N0861 on the negative chronotropic and vasodilatory actions of adenosine in the canine heart were determined. N0861 attenuated the negative chronotropic action of adenosine (1-6 μmol/kg; rapid bolus into the right atrium) on sinus node pacemaker activity in a dose-dependent manner (pA
2
= 4.23). For example, the maximal prolongation of sinus cycle length induced by 6 μmol/kg adenosine was 82 ± 13% under baseline conditions and 57 ± 10, 34 ± 5 and 34 ± 6% during infusion of N0861 at incremental rates leading to plasma levels of 7.75 ± 1.02, 14.15 ± 0.87, and 19.71 ± 1.83 μg/mL, respectively. In contrast, N0861 did not inhibit but had a tendency to potentiate the vasodilatory action of adenosine (thought to be mediated by the A
2
adenosine receptor subtype (A
2
-AdoR)) on the left anterior descending and circumflex coronary arteries. These data indicate that two different receptors, similar to the typical A
1
-AdoR and A
2
-AdoR, mediate the electrophysiologic and vasodilatory actions of adenosine in the canine heart, respectively, and that N0861 is a selective antagonist of adenosine at A
1
-AdoR in the canine heart in vivo.Key words: adenosine, N0861, atrioventricular block, A
1
adenosine receptor, dog heart.
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Details
- Title
- Effects of N6-endonorbornan-2-yl-9-methyladenine, N0861, on negative chronotropic and vasodilatory actions of adenosine in the canine heart in vivo
- Creators
- Amir Pelleg - Cardiovascular Institute of the SouthCarl M Hurt
- Publication Details
- Canadian journal of physiology and pharmacology, v 70(11), pp 1450-1456
- Publisher
- NRC Research Press
- Number of pages
- 7
- Resource Type
- Journal article
- Language
- English
- Web of Science ID
- WOS:A1992KP11800003
- Scopus ID
- 2-s2.0-0027008741
- Other Identifier
- 991019348759004721
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- Web of Science research areas
- Pharmacology & Pharmacy
- Physiology