The Endocannabinoid Reuptake Inhibitor WOBE437 Is Orally Bioavailable and Exerts Indirect Polypharmacological Effects via Different Endocannabinoid Receptors

Endocannabinoid reuptake inhibitor WOBE437, which blocks anandamide (AEA) and 2-arachidonoylglycerol (2-AG) transport, is evaluated for oral bioavailability to the brain and for downstream receptor-specific effects in pain and inflammation. In mice, WOBE437 reaches measurable brain concentrations after oral dosing and is cleared from the brain within a few hours. CB1-dependent effects are observed in an acute analgesia assay (hot plate test) without catalepsy or locomotor effects, supporting functional analgesia rather than general sedation.