CE-123 is a synthetic heterocyclic analogue of modafinil, developed by researchers at the University of Vienna under Peter Kalaba's group. It is the most extensively studied member of a series of structurally related heterocyclic derivatives.
Mechanism of Action
The compound is an atypical dopamine transporter (DAT) inhibitor with an EC50 of 2.76 μM in uptake inhibition assays conducted in HEK293 cells stably expressing human isoforms of DAT. Unlike classical stimulants, CE-123 modulates dopamine reuptake rather than inducing a massive dopamine surge — a property that underlies its favorable tolerability profile. The compound demonstrates a substantially superior blood-brain barrier penetration coefficient (Kp,uu,brain = 0.5) compared to R-modafinil (Kp,uu,brain = 0.1).
Research Data
In animal model studies, (S)-CE-123 demonstrated:
• Improved cognitive flexibility in the ASST without negative effects on impulsivity
• Enhanced spatial working memory in the radial arm maze
• Partial reversal of tetrabenazine-induced motivational deficits in FR5/chow feeding choice and progressive ratio paradigms
• Modulation of D1R receptor expression in the frontal cortex
Potential Therapeutic Applications
The compound is considered a candidate for the treatment of motivational disorders, motivational deficits in depression, schizophrenia, and neurodegenerative diseases. It belongs to the new generation of 'soft' cognitive enhancers with minimal abuse potential.
Physicochemical Properties
White to off-white crystalline solid. Soluble in DMSO (≥10 mg/mL), sparingly soluble in water. Stable at room temperature protected from light. Recommended storage: +4°C or −20°C for long-term storage.
BIOLABCHEMICALS