2-Chloro-N6-cyclopentyladenosine: a highly selective agonist at A1 adenosine receptors

Naunyn Schmiedebergs Arch Pharmacol. 1988 Jun;337(6):687-9. doi: 10.1007/BF00175797.


2-Chloro-N6-cyclopentyladenosine (CCPA) was synthesized as a potential high affinity ligand for A1 adenosine receptors. Binding of [3H]PIA to A1 receptors of rat brain membranes was inhibited by CCPA with a Ki-value of 0.4 nM, compared to a Ki-value of 0.8 nM for the parent compound N6-cyclopentyladenosine (CPA). Binding of [3H]NECA to A2 receptors of rat striatal membranes was inhibited with a Ki-value of 3900 nM, demonstrating an almost 10,000-fold A1-selectivity of CCPA. CCPA inhibited the activity of rat fat cell membrane adenylate cyclase, a model for the A1 receptor, with an IC50-value of 33 nM, and it stimulated the adenylate cyclase activity of human platelet membranes with an EC50-value of 3500 nM. The more than 100-fold A1-selectivity compares favourably with a 38-fold selectivity of CPA. Thus, CCPA is an agonist at A1 adenosine receptors with a 4-fold higher selectivity and 2-fold higher affinity than CPA, and a considerably higher selectivity than the standard A1 receptor agonist R-N6-phenylisopropyladenosine (R-PIA). CCPA represents the agonist with the highest selectivity for A1 receptors reported so far.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine / analogs & derivatives*
  • Adenosine / pharmacology
  • Adenylyl Cyclases / metabolism
  • Adipose Tissue / drug effects
  • Adipose Tissue / metabolism
  • Animals
  • Blood Platelets / drug effects
  • Blood Platelets / enzymology
  • Blood Platelets / metabolism
  • Brain / drug effects
  • Brain / metabolism
  • Corpus Striatum / drug effects
  • Corpus Striatum / metabolism
  • Humans
  • In Vitro Techniques
  • Rats
  • Receptors, Purinergic / drug effects
  • Receptors, Purinergic / metabolism*


  • Receptors, Purinergic
  • 2-chloro-N(6)cyclopentyladenosine
  • Adenylyl Cyclases
  • Adenosine