Agonists

In the case of human, rat, and mouse, CCPA (and to a somewhat lesser extent CPA) represents a selective full agonist at the adenosine A1 receptors. Partial agonists are also available, including compounds substituted in the C8-position (Roelen et al. 1996) or the ribose 5'-substituent (van der Wenden etal. 1998). These compounds show tissue selectivity in vivo. NECA was long considered to be a selective adenosine A2 receptor agonist, but it is now realized that it is nonselective. Based on evidence that 2-substitution of NECA increased selectivity, CGS21680 was developed as an A2a receptor selective agonist (Hutchison et al. 1989). However, in humans it is less potent and less selective than in rats (Kull et al. 1999). There is an additional problem with CGS21680 as a tool: it also binds to sites unrelated to A2a receptors (Johansson etal. 1993b; Cunha etal. 1996; Lindström etal. 1996). This means that at least in organs or cells with few A2A receptors, effects of CGS21680 must be viewed with scepticism. In the case of A2b receptors the most potent agonists have affinities only marginally below 1 ^M. Furthermore, selectivity is negligible. The most potent A3 receptor agonist is Cl-IB-MECA displaying 2500 and 1400 fold selectivity over adenosine A1 and adenosine A2a receptors, respectively.

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