CTP-354

CTP-354 is an orally available, deuterated small-molecule modulator of γ-aminobutyric acid type A (GABAA) receptors, developed by Concert Pharmaceuticals using its deuterated chemical entity platform as an analog of Merck’s preclinical compound L-838417.[1][2][5][11] It binds to the benzodiazepine site of non-α1-containing GABAA receptor subtypes, aiming to retain the anxiolytic, antispastic and muscle relaxant properties of benzodiazepines while minimizing α1-mediated sedation and ataxia.[1][2][5] In Phase 1 studies in healthy volunteers, CTP-354 showed a favorable pharmacokinetic profile with an approximately 20-hour half-life, high and sustained GABAA receptor occupancy, low variability, and once-daily oral dosing without relevant food effect, and was generally well tolerated without dose-limiting sedation or ataxia.[1][6][8] It was initially developed for spasticity, including spasticity associated with spinal cord injury and multiple sclerosis, and was also considered for chronic pain, but clinical development has since been discontinued.[1][4][7][10][11]