Adenosine receptors selective agonists

Melman A, Gao ZG, Kumar D, Wan TC, Gizewski E, Auchampach JA, Jacobson KA (2008) Design of (N)-methanocarba adenosine 5 -uronamides as species-independent A3 receptor-selective agonists. Bioorg Med Chem Ledl8 2813-2819... 

Adenosine derivatives 138 and 139 containing a fused thiirane moiety were synthesized and reported to be a highly potent and selective A1 adenosine receptor (AiAR) agonists. Differences in affinities toward human AjAR and other subtypes of adenosine receptors are more than three orders of magnitude <2004BMC4877>. 

Fig. 4 Selective activation of pulmonary C-flbers arising from the nodose ganglia with either adenosine or 2-methyl-5-hydroxytryptamine (a 5-HT3 receptor selective agonist) markedly inhibits citric acid induced coughing in anesthetized guinea pigs, while intrapulmonary RAR activation by histamine is without effect. Citric acid (0.001-2 M) was applied topically to the tracheal mucosa in 100 — pL ahquots at 1-min intervals and in ascending concentrations. Each bar represents the mean SEM cumulative number of coughs evoked by citric acid in five to six experiments...

Adenosine Receptors. Figure 1 Structures of widely used AR agonists, both nonselective and selective. Affinities/potencies at the ARs are found in Table 2. (a) Nucleoside derivatives that are either nonselective or selective for A receptors (1-12). (b) Nucleoside derivatives that are selective for A2a. A2a/A2b (mixed), or A3 receptors (13-19). 

TABLE 17-2 Subtypes of adenosine receptor, their effectors and selective agonists and antagonists ... 

FIGURE 17-7 The structures of selective agonists and antagonists of adenosine receptors. 

As mentioned above, a key factor in excluding a role for three out of the four recognised adenosine receptor subtypes was that the subtype selective agonists, CPA (Aj), CGS 21680 (A2A) and 2-CI-IB-MECA (A3), unlike the non-selective agonists,... 

Gao Z-G, Kim S-K, Biadatti T, Chen W, Lee K, Barak D, Kim S-G, Johnson CR, Jacobson KA (2002) Structural determinants of A3 adenosine receptor activation nucleoside ligands at the agonist/antagonist boundary. J Med Chem 445 4471-4484 Gao Z-G, Blaustein JB, Gross AS, Melman N, Jacobson KA (2003) M -Substituted adenosine derivatives selectivity, efficacy, and species differences at A3 adenosine receptors. Biochem Pharmacol 65 1675-1684... 

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