A blood-brain barrier-permeable, non-toxic phenyl-pyrazolylurea compound that acts as a direct, potent, fast, and reversible activator of GIRK1 (G-protein activated inward-rectifying K+ channel containing subunit 1) containing channels (EC50 = 162, 914, and 887nM in Thallium influx assay for GIRK1/2, GIRK1/3, and GIRK1/4 expressed in HEK-293 cell lines). Its action does not require the presence of an activated Gi GPCR. Shown to be inactive towards GIRK2, GIRK2/3, Kir2.1, KV7.4 and GABAA, and weakly active against a panel of 61 other receptors, ion channels, enzymes, transporters, and proteins even at higher concentration (~10uM). Exhibits desirable pharmacokinetic properties with good solubility (17.5uM), predicted hepatic clearance (88 ml/min/kg), and Tmax of 640nM and 130nM in plasma and brain, respectively. Shown to reduce locomotor function and seizure frequency in electroshock- and chemically-induced murine epilepsy models (60mg/kg, i.p).
Storage and Stability:May be stored at 4°C. For long-term storage, aliquot and store at 4°C. Do not freeze. For maximum recovery of product, centrifuge the original vial prior to removing the cap. Further dilutions can be made in assay buffer.
