BL 1249
BL 1249 性质
| 沸点 | 492.6±55.0 °C(Predicted) |
|---|---|
| 密度 | 1.291±0.06 g/cm3(Predicted) |
| 储存条件 | -20°C |
| 溶解度 | 二甲基亚砜：~17.5mg/mL |
| 形态 | 固体 |
| 酸度系数(pKa) | 4.10±0.10(Predicted) |
| 颜色 | 粉色至棕色 |
BL 1249 用途与合成方法
EC50: 5.5 μM (TREK-1) and 8.0 μM (TREK-2)
BL-1249 produces a concentration-dependent membrane hyperpolarization of cultured human bladder myocytes, assessed as either a reduction in fluorescence of the voltage-sensitive dye bis-(1,2-dibutylbarbituric acid)trimethine oxonol (
EC
50
of 1.26 μM) or by direct electrophysiological measurement
EC
50
of 1.49 μM). BL-1249 produced a concentration-dependent hyperpolarization with an
EC
50
of 21.0 μM in human aortic smooth muscle cells.
In in vitro organ bath experiments, BL-1249 produces a concentration-dependent relaxation of 30 mM KCl-induced contractions in rat bladder strips (
EC
50
of 1.12 μM), yet has no effect on aortic strips up to the highest concentration tested (10 μM). The bladder relaxation produced by BL-1249 is partially blocked by Ba
2+
(1 and 10 mM).
BL-1249 is a selective agonist of the TREK subfamily when applied extracellularly, having preferential action on K
2P
2.1(TREK-1) and K
2P
10.1(TREK-2) over K
2P
4.1(TRAAK) and establish that its mechanism of action relies on gating at the selectivity filter C-type gate.
BL-1249 (1 mg/kg) inhibits isovolumic bladder contractions in vivo. The short duration of the effect of BL-1249 on bladder contraction ( 30 min) is likely due to a fast elimination half-life of the compound after i.v. administration (0.69 h).
BL-1249 (1 mg/kg) has little effect on mean arterial blood pressure, an observation again consistent with the in vitro bladder to vascular relaxant selectivity.
