Fladrafinil (CRL-40,941)

Fladrafinil, code CRL-40,941, is 2-[bis(4-fluorophenyl)methylsulfinyl]-N-hydroxyacetamide: adrafinil with a fluorine atom on each phenyl ring. It belongs to the modafinil family of wake-promoting compounds, and in volunteers it is converted to flmodafinil (CRL-40,940), its amide counterpart, much as adrafinil is converted to modafinil (Krug et al., 2026). Laboratoire L.

Direct research on fladrafinil is thin, so this guide also uses flmodafinil, adrafinil and modafinil data, labeled as such.

Those, the synonyms and the structure come from PubChem CID 13316557, so the two sources do not conflict.

Relevant work falls into five areas. Each summary names its model and flags data from related compounds.

Origin in the Lafon afinil series

Lafon identified adrafinil in 1974, and its kinetics led to its active metabolite, modafinil (Billiard and Broughton, 2018). In mice, alpha-adrenergic blockers such as prazosin prevented hyperactivity induced by adrafinil, then coded CRL 40028 (Duteil et al., 1979). Lafon's US patent 4,489,095 (Lafon, 1984) then claimed halogenated versions and named the difluoro compound, CRL 40941, the most interesting.

In its tests, CRL 40941 raised spontaneous activity in mice, like adrafinil. When two groups of male mice housed apart were brought together, 64 and 128 mg/kg cut fights by 58 to 61 percent, which adrafinil did not. These are patent data; we found no peer-reviewed study that repeats them. Model: mice.

Metabolism: a prodrug of flmodafinil

The only peer-reviewed study of fladrafinil in a living system is a 2026 doping-control study from Cologne, Germany. Six volunteers each ingested flmodafinil and, three weeks apart, fladrafinil, both as liquid supplements, and the group measured them in urine and dried blood spots. Intact fladrafinil was detectable in urine for up to 12 hours.

Flmodafinil, flmodafinil acid and flmodafinil sulfone also appeared, with flmodafinil peaking several hours later, and stayed detectable for up to 8 days (flmodafinil) and 2 weeks (its acid and sulfone). The authors conclude that fladrafinil is a prodrug of flmodafinil (Krug et al., 2026). Adrafinil follows the same pattern; a doping-control method screens urine for it and its major metabolites, modafinil and modafinil acid (Lu et al., 2009). Model: a human excretion study.

Dopamine transporter data from flmodafinil and modafinil

We found no published binding data for fladrafinil itself. Its conversion product, flmodafinil, bound the dopamine transporter (DAT) in rat brain membranes with a Ki of 2,190 nM, close to 2,520 nM for racemic modafinil, while the dichloro and dibromo analogs bound more tightly, at 919 and 600 nM (Cao et al., 2010). For modafinil, DAT is the best-supported target. Mice lacking DAT did not respond to its wake-promoting action (Wisor et al., 2001). Whether fladrafinil binds DAT before conversion has not been reported. Models: rat brain tissue and knockout mice.

Wakefulness and behavior in animals

Lauflumide (NLS-4), which PubChem lists as a synonym of flmodafinil, was compared with modafinil in C57BL/6J mice by EEG. Mice given 64 mg/kg NLS-4 stayed awake longer than mice given 150 mg/kg modafinil, neither group showed rebound sleep, and recovery sleep after NLS-4 held less NREM sleep and delta activity. The authors note that Lafon conceived the compound but never developed it (Luca et al., 2018).

Adrafinil data point both ways. In aged beagle dogs, 20 mg/kg adrafinil given 2 hours before training cut the errors and trials needed to learn a discrimination task (Milgram et al., 2000), yet the same amount raised errors on a delayed nonmatching-to-position working memory task (Siwak et al., 2003). No comparable data exist for fladrafinil. Models: mice and aged dogs.

Analytical chemistry and doping control

Heat breaks fladrafinil down. In a gas chromatograph's heated inlet, CRL-40,941, CRL-40,940 and N-methyl-4,4-difluoromodafinil formed a tetrafluoro analog of 1,1,2,2-tetraphenylethane, and the authors warn that routine GC-MS analysis can be ambiguous (Dowling et al., 2017). A US food-testing laboratory validated an LC-HRMS method for modafinil and four analogs, including CRL-40,940 and CRL-40,941, then found adrafinil in all four adrafinil-labeled nootropic products it bought (Bakota and Nandrea, 2025).

The Cologne urine method detects fladrafinil down to 0.2 ng/mL, and none of about 2,000 elite-athlete urine samples from 2023 and 2024 contained either compound or their metabolites (Krug et al., 2026). Models: reference material, commercial products, urine and blood.