Here, we present the preclinical pharmacological characterization of SYT-510, the first clinical candidate in a new class of Selective Endocannabinoid Reuptake Inhibitors (SERIs), across multiple CNS models.

In vitro assays were employed to characterize SYT-510’s mode of action and specificity. Ex vivo electrophysiological recordings in brain slices were used to gain insight on the neuromodulatory function of SERIs. In vivo animal models were utilized to study the efficacy of SYT-510 on symptoms relevant to CNS disorders.

SYT-510 inhibited the uptake of both major endocannabinoids (eCBs) AEA and 2-AG in immune and neuronal cells with high selectivity. In brain slices, SYT-510 effectively modulated CB1 receptor-mediated short-term synaptic plasticity in regions relevant to movement, learning and memory, seizure and anxiety. SYT-510 was effective in multiple animal models of anxiety, compulsive behavior, drug-induced muscle spasticity, seizure, pain and multiple sclerosis. The pharmacological effect was evident after single administrations as well as upon chronic treatment without any signs of tolerance. It correlated with moderate increases in eCB levels, which proved to be sufficient to fully activate the ECS without eliciting sedation, abuse potential and the typical psychotropic effects associated with exogenous activation of CB1 receptor

SYT-510 is the first candidate of SERIs, a novel class of ECS modulators that potently and selectively inhibit eCB reuptake, thereby rebalancing and gently enhancing the ECS to ultimately restore normal brain function under disease conditions. SERIs show broad therapeutic potential across multiple neurological and psychiatric disorders. SYT-510 is currently in Phase 2 clinical development.