TPPU is suitable for investigating soluble epoxide hydrolase biology and the role of epoxide-containing lipids in modulating inflammatory diseases. TPPU displays high plasma concentrations when dosed orally at 0.3 mg/kg and drug-like properties. The Cmax increases with dose from 0.3 to 3 mg/kg for TPPU. Following administration in drinking water to rats (0.2, 1, and 5 mg TPPU/L with 0.2% PEG400), TPPU’s blood concentration increases dose dependently within the treatment period to reach an almost steady state after 8 days. The sEH inhibitor, TPPU, shows antidepressant effects in animal models of depression. Expression of sEH protein is increased in the brain of chronically stressed mice and depressed patients. Prophylactic sEH inhibition or sEH-KO results in resilience to repeated social defeat stress, associated with increased BDNF-TrkB signaling in prefrontal cortex and hippocampus of KO mice.
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