Percentages of activation or inhibition in Ca2+ microfluorometry assays of TRPV1, TRPV3, TRPA1, TRPM3, and ASIC3 channels selected β-lactams (10 µM)
| Compound | Config | hTRPV1 agonism (%) | hTRPV1 antagonism (%) | hTRPV3 antagonism (%) | hTRPA1 agonism (%) | hTRPA1 antagonism (%) | hTRPM3 antagonism (%) | ASIC3 antagonism (%) |
|---|---|---|---|---|---|---|---|---|
| 1a | 3S,4S,2'S | 31.3 ± 3.6 | 19.4 ± 1.7 | –6.3 ± 5.9 | 0.4 ± 0.3 | 4.2 ± 1.1 | ND | 6.0 ± 0.9 |
| 1b | 3S,4S,2'R | 4.7 ± 3.6 | –9.4 ± 15.1 | –6.6 ± 2.9 | 0.4 ± 0.2 | –2.4 ± 7.5 | 8.9 ± 8.8 | –10.1 ± 8.9 |
| 1c | 3R,4R,2'S | 63.7 ± 3.1 | 52.6 ± 17.0a | 6.6 ± 2.5 | 0.7 ± 0.1 | –13.1 ± 8.8 | 7.5 ± 10.3 | ND |
| 1d | 3R,4R,2'R | –2.2 ± 3.2 | –1.5 ± 0.8 | 11.2 ± 3.0 | 0.2 ± 0.6 | –6.1 ± 4.9 | 8.5 ± 1.8 | ND |
| 9d | 3R,4R,2'R | 4.9 ± 0.6 | –8.8 ± 2.9 | 0.1 ± 0.9 | 1.3 ± 0.2 | 7.8 ± 0.6 | 10.6 ± 2.9 | ND |
| 11a | 3S,4S,2'S | 26.7 ± 3.1 | 46.4 ± 0.4a | 7.1 ± 0.4 | 1.1 ± 0.4 | 9.5 ± 3.4 | 19.9 ± 6.6 | 2.1 ± 6.2 |
hTRPV1: human transient receptor potential vanilloid, type 1; hTRPA1: human transient receptor potential ankirin, type 1; hTRPM3: human transient receptor potential melastatin, subtype 3; ASIC3: acid sensing ion cannel, subunit 3; IC50: concentration exerting a half-maximal inhibition; ND: no data. In all cases, data is from two experiments in duplicate. Agonism: assay for agonist activity. Antagonism: assay for antagonist activity (see Materials and methods). Agonists used for activation of the different channels: TRPV1 (capsaicin, 30 nM), TRPV3 [2-aminoethoxydiphenyl borate (2-APB), 30 µM], TRPA1 (allylisothiocyanate, 10 µM), TRPM3 (pregnenolone sulfate, 50 µM), ASIC3 (buffer, pH 5.5). Antagonists used as references: TRPV1 (capsazepin, IC50 1.3 × 10−7 M), TRPV3 (ruthenium red, IC50 2.5 × 10−7 M), TRPA1 (ruthenium red, 10 µM), TRPM3 (isosakuranetin, 10 µM; IC50 50 nM), ASIC3 (amiloride, 1 mM). ª The observed antagonism could be due, at least in part, to desensitization, since the compound is able to activate the receptor > 20%