BL 1249

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.