N-[(2,4-difluorophenyl)methyl]-2'-{[2-(4-methoxyphenyl)acetamido]methyl}-[1,1'-biphenyl]-2-carboxamide

Biological Activity

Potent and selective TASK-1 potassium channel blocker th at induces lasting respiratory alkalosis and stimulates breathing in anesthetized rats.




A1899 is a highly potent and selective non-voltage-dependent two-pore domain potassium channel K 2P 3.1 blocker (TASK-1, KCNK3, IC50 = 7 nM in CHO cells) with 10-fold selectivity over TASK-3 and much reduced or little potency towards TASK-2/4 (>8 μM in Xenopus oocytes) and other potassium channels. A1899 specifically blocks TASK-1 currents by 74% in Xenopus oocytes at 100 nM via an open-channel block mechanism. A1899 induces lasting respiratory alkalosis and stimulates breathing in anesthetized rats in vivo (5-25 mg/kg, i.v.). Also mitigates the endothelin-1 induced prolonged action potential duration in cardiomyocytes ( at 200 nM).

storage

Store at -20°C