CLP290 is an activator of the neuron-specific K+-Cl cotransporter KCC2 and displays potential for the treatment of a wide range of neurological and psychiatric indications.

In vivo co-treatment with morphine and oral CLP290 prevented membrane KCC2 downregulation in SDH neurons.?Concurrently, co-treatment with CLP290 significantly mitigated MIH and acute administration of CLP257 in established MIH restored normal nociceptive behavior.

Morphine sulfate (50 mg/ml) was diluted in saline sterile solution immediately before injection.?Morphine or saline were subcutaneously injected twice a day (10 mg/kg;?9 a.m. 6 p.m.) in na?ve adult rats.?The KCC2 enhancer CLP257 and its carbamate pro-drug CLP290 were freshly diluted in 20% 2-hydroxypropyl-β-cyclodextrin (HPCD) prior injection.?CLP257 or vehicle were delivered intraperitoneally after 7 8 days of morphine or saline, as described (100 mg/kg).?CLP290 or vehicle were delivered orally by gavage twice a day for the whole duration of the morphine/saline treatment (100 mg/kg).