Table 1.
Binding affinities and EC50/IC50 values of RO5166017 at rodent and primate TAAR1
| Parameter, assay, preparation | Mouse | Rat | Human | Cynomolgus monkey |
| Ki, binding, HEK293* | 1.9 ± 1.2 | 2.7 ± 1.3 | 31 ± 4 | 24 ± 5 |
| EC50, cAMP, HEK293† | 3.3 ± 1.7 (65 ± 15%) | 14 ± 10 (90 ± 17%) | 55 ± 27 (95 ± 8%) | 97 ± 53 (81 ± 1%) |
| EC50, GIRK, Xenopus oocytes‡§ | 8.0 ± 1.2 (72 ± 2%) | n.d. | n.d. | n.d. |
| IC50, patch clamp, VTA slices§ | 1.73 | n.d. | n.d. | n.d. |
| IC50, patch clamp, DRN slices§ | 2.99 | n.d. | n.d. | n.d. |
Values (in nM) represent the mean ± SEM from at least three independent experiments. Data in parentheses represent the maximal efficacy relative to PEA (EC50 and cAMP) or pTyr (EC50 and GIRK). n.d., not determined.
*Radioligand [3H]RO5166017 for mouse and rat TAAR1 and [3H]RO5192022 for human and cynomolgus monkey TAAR1.
†Upstate (Millipore) immunoassay for cAMP.
‡Current mediated by Kir3.1 and Kir3.2 coexpressed with TAAR1.
§Current at −50-mV holding potential.