N-0861 selectively antagonizes adenosine A1 receptors in vivo.

Experiments were performed to determine the antagonistic actions of (+/-)N6-endonorbornan-2-yl-9-methyladenine (N-0861) at A1 and A2 adenosine receptors in vivo, and to evaluate the pharmacodynamics of the observed responses. 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). N-0861, at doses greater than or equal to 1 mumol/kg + 0.04 mumol/kg per min, i.v. produced dose-related rightward shifts of the A1 dose-response curve, but had no effect on the A2 dose-response curve at doses as high as 100 mumol/kg, i.v. In contrast, the non-selective A1/A2 adenosine receptor antagonist 8-phenyltheophylline antagonized both A1 and A2 receptor-mediated responses to adenosine. The minimum effective i.v. dose and the duration of action of N-0861 were determined by evoking bradycardic responses to i.v. adenosine (A1 effect) in anesthetized, vagotomized, beta-blocked rats before and after single bolus doses of vehicle or N-0861 (0.3, 0.6, 1.0, 3.0 or 10.0 mumol/kg). The lowest i.v. dose of N-0861 to antagonize A1 receptor-mediated bradycardia was 0.3 mumol/kg i.v.; the duration of effect ranged from 1 min (following 0.3-1 mumol/kg) to approximately 2.5 h (following 10 mumol/kg). N-0861 is a selective (by greater than or equal to 333-fold) antagonist of adenosine A1 receptors.
AuthorsR J Barrett, D A Droppleman, K F Wright
JournalEuropean journal of pharmacology (Eur J Pharmacol) Vol. 216 Issue 1 Pg. 9-16 (May 27 1992) ISSN: 0014-2999 [Print] Netherlands
PMID1526257 (Publication Type: Journal Article)
Chemical References
  • Norbornanes
  • Purinergic Antagonists
  • N 0861
  • Theophylline
  • 8-phenyltheophylline
  • Adenine
  • Adenosine
  • Adenine (analogs & derivatives, pharmacology)
  • Adenosine (pharmacology)
  • Animals
  • Dose-Response Relationship, Drug
  • Heart Rate (drug effects)
  • Injections, Intravenous
  • Male
  • Norbornanes (pharmacology)
  • Purinergic Antagonists
  • Rats
  • Rats, Inbred Strains
  • Theophylline (analogs & derivatives, pharmacology)
  • Vasodilation (drug effects)

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