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

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Summary

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 K i-value of 0.4 nM, compared to a K i-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 K i-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.

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Abbreviations

CCPA:

2-choro-N6-cyclopentyladenosine

CPA:

N6-cyclopentyladenosine

NECA:

5′-N-ethylcarboxamidoadenosine

PIA:

N6-phenylisopropyladenosine

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Lohse, M.J., Klotz, KN., Schwabe, U. et al. 2-Chloro-N6-cyclopentyladenosine: a highly selective agonist at A1 adenosine receptors. Naunyn-Schmiedeberg's Arch Pharmacol 337, 687–689 (1988). https://doi.org/10.1007/BF00175797

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  • DOI: https://doi.org/10.1007/BF00175797

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