Table 2.
TREK-1 activators.
| Molecule | EC50 | Cell type | Specificity | References | |
|---|---|---|---|---|---|
| Neuroprotective agents | Riluzole | Transient activation (100 μM tested) | COS cells | Activates TRAAK (EC50∼60 μM), blocks TTX-sensitive (IC50 = 90 μM) and TTX-resistant (IC50 = 143 μM) sodium channels. It antagonizes Ca2+ entry induced by glutamic acid (IC50 = 0.30 ± 0.07 μM) or by NMDA (IC50 = 12.8 ± 2.4 μM). Riluzole inhibits glutamate release in the caudate nucleus (10 μM tested) and the hippocampus (10–30 μM tested) | Cheramy et al., 1992; Martin et al., 1993; Hubert et al., 1994; Song et al., 1997; Duprat et al., 2000 |
| Mood stabilizers | Lithium | Maximum of activation at 1 mM | HEK293 cells | nd | Kim et al., 2017 |
| Gabapentin | 100μM tested | nd | Kim et al., 2017 | ||
| Valproate | 100 μM tested | nd | Kim et al., 2017 | ||
| Carbamazepine | Maximum of activation at 100 μM | nd | Kim et al., 2017 | ||
| Carbazole-based | ML67 | EC50 = 213 ± 1.2 μM | Xenopus oocytes | Activates TREK-2 (EC50∼250 μM) and TRAAK | Bagriantsev et al., 2013 |
| ML67-33 | EC50 = 36.3 ± 1 μM | Xenopus oocytes | Activates TREK-2 (EC50 = 30.2 ± 1.4 μM) and TRAAK (EC50 = 27.3 ± 1.2 μM) | ||
| EC50 = 9.7 ± 1.2 μM | HEK293 | ||||
| ML335 | EC50 = 14.3 ± 2.7 μM | Xenopus oocytes | Activates TREK-2 (EC50 = 5.2 ± 0.5 μM), no effect on TRAAK | Lolicato et al., 2017 | |
| EC50 = 5.2 ± 0.8 μM | HEK293 | ||||
| ML402 | EC50 = 13.7 ± 7 μM | Xenopus oocytes | Activates TREK-2 (EC50 = 5.9 ± 1.6 μM), no effect on TRAAK | ||
| EC50 = 5.9 ± 1.6 μM | HEK293 | ||||
| Polyunsaturated fatty acids (PUFA) | Arachidonic acid | (0.1–10 μM) tested | COS cells | Activates TREK-2 (1–10 μM), no effect on TRAAK (0.01–100 μM) | Patel et al., 1998 |
| General volatile anesthetics | Chloroform | (0.2–1.6 mM) | COS cells | Selective for TREK-1 | Patel et al., 1999 |
| Halothane | (0.04–4 mM) | Activates TASK channels | |||
| Isoflurane | 2 mM tested | Activates TASK channels | |||
| Diethyl ether | 0.8 mM tested | Decrease TASK channel activity | |||
| Analgesics (NSAIDs) | Fenamate | EC50∼100 μM | COS cells | Activates TREK-2 (EC50∼100 μM) and TRAAK (>100 μM) | Takahira et al., 2005 |
| Flufenamic acid | 250 ± 35% at 100 μM | TsA201 cells | nd | Veale et al., 2014 | |
| Tetrazole-based | BL-1249 | EC50 = 1.49 ± 0.08 μM | Cultured human urinary bladder myocytes | nd | Tertyshnikova et al., 2005 |
| EC50 = 2 ± 2 μM | Pancreatic ductal adenocarcinoma | nd | Sauter et al., 2016 | ||