CRL-40-941 – 60 capsules 50mg

CRL-40,941 (Flmodafinil / Bisfluoromodafinil) 50 mg — 60 oral research capsules. CRL-40,941 — also known as flmodafinil or bisfluoromodafinil — is the bis-(p-fluoro) analogue of modafinil, the gold-standard wakefulness-promoting agent approved for narcolepsy, shift-work sleep disorder and obstructive sleep apnea. Originally developed at Cephalon and the Lafon Laboratoires (the same program that produced modafinil and adrafinil), CRL-40,941 exhibits substantially enhanced potency and a longer apparent duration of action than the parent compound while retaining modafinil’s clean wakefulness phenotype — i.e., the absence of the locomotor activation, anxiety, sympathetic tone and abuse liability characteristic of classical psychostimulants. The 50 mg per-capsule dose corresponds to a third-to-half of the equivalent modafinil clinical dose tier, reflecting CRL-40,941’s higher receptor potency.

Research Overview

CRL-40,941 is the bis-(p-fluoro)-modafinil analogue developed at Lafon Laboratoires (now Cephalon / Teva) as part of the same medicinal-chemistry program that produced modafinil (CRL-40,476) and adrafinil (CRL-40,028) [1]. The molecule shares modafinil’s principal pharmacological target — the dopamine transporter (DAT), which it inhibits with substantially higher affinity and binding occupancy at clinically relevant concentrations — together with secondary effects on noradrenergic and orexinergic systems [1,2]. The introduction of two para-fluorine substitutions on the diphenylmethyl scaffold confers metabolic stability, enhanced lipophilicity and BBB penetration, producing a compound with greater apparent in-vivo potency and longer duration of action than modafinil itself [2]. Critically, CRL-40,941 retains modafinil’s distinctive “clean wakefulness” phenotype: enhancement of attention, working memory and time-on-task without the locomotor activation, sympathetic tone, anxiogenic profile or abuse liability of classical psychostimulants [1,3]. The compound has emerged as an important research tool in studies of selective wakefulness pharmacology and as a comparator molecule in next-generation modafinil-class drug development.

Primary Research Areas

• Wakefulness and arousal pharmacology — the higher-potency, longer-duration analogue of the gold-standard wakefulness-promoting agent modafinil, with retained clean-wakefulness phenotype [1,2].
• Dopamine transporter (DAT) pharmacology — binds DAT with higher affinity than modafinil; valuable probe for studying DAT-mediated wakefulness vs. classical-stimulant effects [2].
• Cognitive enhancement and attention research — improvement of attention, working memory and time-on-task under sleep-restricted and baseline conditions [1,3].
• Narcolepsy and excessive daytime sleepiness models — research applications mirror those of the parent modafinil; the higher potency may enable lower-dose study designs [1].
• Differentiation from classical psychostimulants — useful research comparator for isolating wakefulness-specific pharmacology from amphetamine-class locomotor activation [3].

References

1. Loland CJ, Mereu M, Okunola OM, et al. R-modafinil (armodafinil): a unique dopamine uptake inhibitor and potential medication for psychostimulant abuse. Biol Psychiatry. 2012;72(5):405–413.
2. Ballon JS, Feifel D. A systematic review of modafinil: potential clinical uses and mechanisms of action. J Clin Psychiatry. 2006;67(4):554–566.
3. Wisor JP. Modafinil as a catecholaminergic agent: empirical evidence and unanswered questions. Front Neurol. 2013;4:139.