CE-123 powder (S-CE-123)

What is CE-123

CE-123 (5-((benzhydrylsulfinyl)methyl)thiazole) is a synthetic heterocyclic analogue of modafinil developed by Peter Kalaba's group at the University of Vienna. It is the most extensively studied and most potent member of a series of structurally related heterocyclic derivatives.

Mechanism of Action The compound is an atypical dopamine transporter (DAT) inhibitor with EC₅₀ ≈ 2.76 μM in reuptake inhibition assays in HEK293 cells stably expressing human DAT isoforms. Ultraselectivity for DAT over NET and SERT distinguishes CE-123 from modafinil, which acts on all three transporters. Rather than triggering a dopamine surge, CE-123 modulates reuptake — a property that underlies its favorable safety profile: no euphoria, no dependence.

BBB Penetration CE-123 achieves a brain unbound-to-plasma unbound concentration ratio Kp,uu,brain = 0.5, versus 0.1 for R-modafinil — fivefold greater availability in brain tissue at equivalent peripheral concentrations.

Preclinical Data (S)-CE-123 reverses tetrabenazine-induced dopamine depletion in FR5/chow and progressive ratio paradigms, restoring effort-based motivation without affecting general locomotor activity. In the ASST, it improves cognitive flexibility without negative effects on impulsivity. In the radial arm maze, it enhances spatial working memory. Daily single dosing improves both memory acquisition and retrieval without signs of tolerance.