CRL-40-941 50 mg – 60 capsules

CRL-40,941 (Fladrafinil / Bisfluoroadrafinil) 50 mg — 60 research capsules. CRL-40,941 — also known as fladrafinil or bisfluoroadrafinil — is the bis-(p-fluoro) analogue of adrafinil and a close relative 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 Laboratoire L. Lafon (the same program that produced modafinil and adrafinil), CRL-40,941 belongs, like adrafinil, to the modafinil class of wakefulness-promoting agents, characterised by the absence of the locomotor activation, anxiety, sympathetic tone and abuse liability typical of classical psychostimulants; direct published data on CRL-40,941 itself are limited.

Research Overview

CRL-40,941 is the bis-(p-fluoro)-adrafinil analogue developed at Laboratoire L. Lafon (now Cephalon / Teva) as part of the same medicinal-chemistry program that produced modafinil (CRL-40,476) and adrafinil (CRL-40,028) [1]. Compounds of this class act principally at the dopamine transporter (DAT), with secondary effects on noradrenergic and orexinergic systems [1,2]; comparable binding data for CRL-40,941 itself have not been published. The two para-fluorine substitutions on the diphenylmethyl scaffold distinguish it from adrafinil and are expected to increase lipophilicity and metabolic stability. Modafinil-class compounds show a 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 — a bis-fluorinated analogue of adrafinil within the modafinil class of wakefulness-promoting agents [1,2].
• Dopamine transporter (DAT) pharmacology — a comparator for studying DAT-mediated wakefulness versus classical-stimulant effects within the modafinil class [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 modafinil and adrafinil [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.