Table 1.
Affinities of selected AR ligands (Ki, nM) that have been used to define adenosinergic activities of non-adenosine receptor drugs (refer to Figure 2 for most structures). Species are human (h), unless noted (m, mouse; r, rat). Values shown and for other compounds in Figure 2 are in Müller and Jacobson; Carlin et al.; Wan et al.; Tosh et al.; Alnouri et al. [22,23,24,25,26]. Values that represent >100-fold selectivity are shown in bold italics.
| Compound | A1AR | A2AAR | A2BAR | A3AR |
|---|---|---|---|---|
| Agonists | ||||
| Adenosine 1 | ~100 73 (r) |
310 150 (r) |
15,000 5100 (r) |
290 6500 (r) |
| R-PIA 4 | 2.04 1.2 (r) |
220 (r) | 150,000 | 33 158 (r) |
| CGS21680 8 | 289 193 (m) |
27 10 (m) |
>10,000 | 67 48 (m) |
| Regadenoson 9 | >16,000 7.75 (m) |
290 77.2 (m) |
>10,000 >100,000 (m) |
>10,000 >10,000 (m) |
| Bay60-6583 a 12 | >10,000 351 (m) |
>10,000 >10,000 (m) |
3–10 136 (m) |
>10,000 3920 (m) |
| IB-MECA 13 | 51 5.9 (m) |
2900 ~1000 (m) |
11,000 | 1.8 0.087 (m) |
| Cl-IB-MECA 14 | 220 35 (m) |
5360 ~10,000 (m) |
>10,000 | 61.4 0.18 (m) |
| Antagonists | ||||
| Caffeine 23 | 10,700 | 24,300 | 33,800 | 13,300 >100,000 (r) |
| 8-SPT 24 | 537 (m) | 12,400 (m) | 4990 (m) | >10,000 (m) |
| XAC 25 | 6.8 1.2 (r), 2.2 (m) |
18.4 63 (r), 83 (m) |
7.75 63 (r), 4.5 (m) |
25.6 29,000 (r), ~10,000 (m) |
| DPCPX 26 | 3.0 1.5 (m) |
129 598 (m) |
51 86.2 (m) |
795 >10,000 (r, m) |
| CSC b | 28,000 (r) | 54 (r) | 8200 (r) | >10,000 (r) |
| SCH442416 28 | 1110 765 (m) |
4.1
1.27 (m) |
>10,000 | >10,000 >10,000 (m) |
| ZM241385 32 | 774 249 (m) |
1.6 0.72 (m) |
75 31 (m) |
743 10,000 (m) |
| MRS1220 38 | 81 (m) | 9.1 (m) | ND | >10,000 (m) |
| 305 (r) | 52 (r) | ND | 0.65 (h) | |
| MRS1523 39 | >10,000 15,600 (r) 5330 (m) |
3660 2050 (r) >10,000 (m) |
>10,000 >10,000 (m) |
18.9 113 (r) 702 (m) |
Notes: a—may be antagonist at A1AR and A3AR, partial agonist at A2BAR; b—CSC (structure not shown) has a second activity to inhibit monoamine oxidase: Ki MAO-B, 80.6 nM. ND, not determined.