Fladrafinil (CRL-40,941)

Identity, and the one atom that separates two compounds

Three names point at the same molecule here. Fladrafinil, the development code CRL-40,941 and the alternative name fluorafinil all sit on a single PubChem record, CID 13316557, so nothing is distinguished by the choice of label. That record carries CAS 90212-80-9, molecular formula C15H13F2NO3S, molecular weight 325.3, InChIKey VKGUUSVYPXTWMA-UHFFFAOYSA-N and UNII 5RT6X0M01F, under the IUPAC name 2-[bis(4-fluorophenyl)methylsulfinyl]-N-hydroxyacetamide. What separates the structure from adrafinil is small and precise: a fluorine added at the para position of each phenyl ring.

Flmodafinil is a different compound and has its own record: CID 13271852, CAS 90280-13-0, C15H13F2NO2S, molecular weight 309.3, code CRL-40,940, also indexed as lauflumide. One oxygen separates the two. Fladrafinil carries a hydroxyl on the amide nitrogen; flmodafinil does not. The pair stands in the same relation as adrafinil (CID 3033226, CAS 63547-13-7, CRL-40028) stands to modafinil, and the two Lafon code numbers differ by one digit. Vendor listings, aggregator pages and forum posts move between the two names freely, and a claim attached to one of them is frequently a claim measured on the other.

A ChEMBL search for fladrafinil returns no molecule record at all. Flmodafinil has one, CHEMBL1672359, carrying eight indexed bioactivity measurements. The FDA Global Substance Registration System holds a substance record for fladrafinil under UNII 5RT6X0M01F; that record is an identifier assignment and carries no marketing authorisation with it. No regulator in any jurisdiction has approved the compound for human use.

What the 1984 patent measured, and what it did not

US Patent 4,489,095, Halogenobenzhydrylsulfinylacetohydroxamic acids, names Louis Lafon as inventor and Laboratoire L. Lafon as assignee, with a priority date of 4 June 1982, a filing date of 26 May 1983 and a grant date of 18 December 1984. Fladrafinil is Example 1, code CRL 40941, melting point 90 to 91 degrees Celsius. Every pharmacological result in the document was produced by intraperitoneal injection of a gum arabic suspension, at 20 mL/kg in the male mouse and 5 mL/kg in the male rat. That document remains the only source of pharmacological data on the molecule itself.

The inter-group aggression test is the experiment the patent was built around. Groups of three male mice spent three weeks either side of an opaque partition, four cages per compound per dose against six control cages. Half an hour after injection the partition was removed and fights were counted over ten minutes. Fladrafinil changed the fight count by minus 58 per cent at 64 mg/kg, minus 61 per cent at 128 mg/kg and minus 20 per cent at 256 mg/kg, a dose the patent notes excites the mice. Adrafinil, run alongside, gave plus 2 per cent, minus 3 per cent and plus 36 per cent at the same three doses. The patent presents this difference as the basis of the invention.

Other readouts in the document are brief. Spontaneous motility rose at 64 and 256 mg/kg with six mice per batch against twelve controls. Motor recovery after acute hypobaric anoxia improved at 16, 64 and especially 256 mg/kg, ten mice per dose against twenty controls. Barbital-induced sleep was shortened at 64 and 128 mg/kg in batches of ten. In batches of six rats, 128 mg/kg prolonged apomorphine and amphetamine stereotypies, which adrafinil at 256 mg/kg did not. The maximum non-lethal dose by that route in the male mouse was above 512 mg/kg; a third of mice given 1024 mg/kg died within 24 hours.

Absent from the patent: any receptor or transporter binding assay, any pharmacokinetic measurement, any repeat-dose or chronic experiment, and any learning, memory or attention task. The word nootropic does not appear. What does appear, at the end of the pharmacology, is a clinical assertion with no experiment behind it. The patent states that fladrafinil acts at doses which are half those of adrafinil, and that excellent results were obtained in man in the treatment of hypersomnia and psychasthenia. No population, no sample size, no design, no endpoint and no publication accompanies that sentence.

The one human administration study, and what it was for

Krug and colleagues published the first human data on fladrafinil in Drug Testing and Analysis in August 2026. The study was run at the Center for Preventive Doping Research at the German Sport University Cologne under ethics approval 089/2021, and its purpose was analytical: to establish how long the compound and its metabolites remain detectable in doping control samples. Six volunteers, three male and three female, each took a single 20 mg oral dose of a commercially purchased liquid supplement, gave dried blood spots and urine over at least 48 hours, and after a three-week washout repeated the protocol with the other compound.

Maximum urinary fladrafinil concentrations across the six ranged from 52 to 111 ng/mL, reached at two or four hours. In dried blood spots the maximum was 11 to 35 ng/mL at two or three hours. The parent compound stayed detectable in urine for up to 12 hours and in blood spots for 8 to 12 hours. Its metabolites lasted much longer: flmodafinil for up to 8 days in urine, flmodafinil acid and flmodafinil sulfone for up to two weeks. The report identifies flmodafinil, flmodafinil acid and flmodafinil sulfone in post-administration samples and describes fladrafinil as a prodrug metabolised to flmodafinil, with the metabolite's peak arriving several hours after the parent's.

Nothing in that study measured an effect. There is no cognitive endpoint, no sleep or wakefulness measurement, no vital sign, no laboratory chemistry and no adverse-event table; the paper does not report tolerability at all. The authors state plainly that the number of subjects is limited and that statements about maximum concentrations or the size of the detection windows should be treated with caution. A separate part of the same work retrospectively screened roughly 2000 anonymised elite athlete urine samples collected between January 2023 and December 2024 and found neither parent compound nor any main metabolite.

The pharmacology on record belongs to the metabolite

No binding assay, transporter assay or electrophysiological measurement of fladrafinil itself was located in PubMed, Europe PMC or ChEMBL. Every mechanistic number that circulates under its name was measured on flmodafinil or on modafinil. Cao and colleagues 2011 reported the bis(4-fluorophenyl) sulfinylacetamide, their compound 5b, displacing radioligand at the dopamine transporter in rat brain membranes with a Ki of 2190 plus or minus 139 nM, with no displacement at the serotonin or noradrenaline transporters up to 10 micromolar. Racemic modafinil in the same table gave 2520 plus or minus 204 nM. On that measurement the fluorinated amide and modafinil are close to equipotent.

Wake-promoting data exist for the (R)-enantiomer of the metabolite in mice. Luca and colleagues 2018 gave male C57BL/6J mice, eight per group, aged 10 to 11 weeks, a single intraperitoneal injection at light onset and recorded EEG and EMG for 24 hours. The material tested there was prepared by asymmetric oxidation of the thioether intermediate into the (R)-sulfoxide by the Kagan method, so it was a single enantiomer rather than the racemate PubChem indexes as flmodafinil. That enantiomer at 64 mg/kg produced a longer net increase in wakefulness than modafinil at 150 mg/kg, 151.18 plus or minus 15.33 minutes against 109.67 plus or minus 16.59 minutes, p below 0.05. Recovery sleep after it contained less NREM sleep and a shorter-lived rise in delta power than after modafinil. That paper calls the compound lauflumide and never uses the names flmodafinil or CRL-40,940.

Separate work at the NIDA Intramural Research Program characterised resolved enantiomers rather than the racemate. Keighron and colleagues 2019 compared R-modafinil with the (S)- and (R)-enantiomers of para-bis(4-fluorophenyl) modafinil, which they designate JBG1-048 and JBG1-049 respectively, in male Sprague-Dawley rats by intravenous cumulative dosing of 10 to 32 mg/kg, using fast-scan cyclic voltammetry and microdialysis across 22 animals. All three raised extracellular dopamine in the nucleus accumbens shell. At the top cumulative dose of 32 mg/kg the two fluorinated enantiomers produced larger maximum dopamine increases than R-modafinil, a 308 per cent increase for JBG1-048 and a 279 per cent increase for JBG1-049, against a maximum of about 220 per cent of basal values for R-modafinil; the paper states the first two as per cent increase and the third as per cent of basal values, and those units are carried through as written rather than converted. The three differed in onset and duration. Those are single enantiomers of the amide, two steps removed from what is sold as fladrafinil.

What analysis of the products has found

Bakota and Nandrea published a validated LC-HRMS method in the Journal of Dietary Supplements in 2025, developed at the FDA Kansas City Human and Animal Food Laboratory. It quantifies modafinil alongside four unscheduled analogues: adrafinil, CRL-40,940, CRL-40,941 and N-methyl-4,4-difluoromodafinil. Applied to four products bought undercover and marketed as nootropics, all four of which were labelled to contain adrafinil, the method found adrafinil in every sample. The paper describes analogues of modafinil, adrafinil included, as unapproved and unscheduled, and points to the absence of scheduling as what makes them a target for inclusion in supplements.

Label accuracy in this category has been measured twice, on two products. Krug and colleagues quantified the content of both supplements before dosing volunteers. The fladrafinil product was labelled at 100 mg/mL and assayed at 93.1 mg/mL. The flmodafinil product was labelled at 50 mg/mL and assayed at 95.7 mg/mL, close to double its stated strength; the administered volumes were adjusted accordingly. No other compounds were detected in either. Two products is not a survey, and the direction of error in one of them was upward by a factor near two.

Identification of these compounds carries an analytical trap. Dowling and colleagues 2017 heated modafinil, modafinic acid, adrafinil, CRL-40,940 and CRL-40,941 in a gas chromatograph injection port and found they degrade there, the fluorinated members forming a tetrafluoro analogue of 1,1,2,2-tetraphenylethane. Running a mixture of a non-fluorinated and a fluorinated compound produced a third, cross-reaction product. A GC-MS result on this chemical family can describe the injector rather than the sample.

Legal and anti-doping position

Flmodafinil and fladrafinil were added to the 2026 edition of the World Anti-Doping Agency Prohibited List, in force from 1 January 2026. Both appear under class S6, stimulants, in the section listing additional examples of substances already prohibited, identified by name and by full chemical name. S6 stimulants are prohibited in competition. Neither the list entry nor the national anti-doping summary cited here states a reason for naming them, and no source giving one was located.

Registered clinical research does not exist. A ClinicalTrials.gov search returns zero studies for fladrafinil, zero for CRL-40941, and zero for flmodafinil, lauflumide and NLS-4 alike. No dose-ranging, pharmacokinetic, safety or efficacy study of the compound in people has been registered there, and the only human administration on record was a six-person analytical study run to support doping control. Napoletano and colleagues 2020 catalogued fladrafinil among 142 cognitive enhancers identified by a web crawler on psychonaut forums, most of which appeared in neither the EMCDDA nor the UNODC database at the time.

What is not known

The pharmacological record for this molecule is one patent and one excretion study. Nothing else was located. There is no measured receptor or transporter affinity for fladrafinil at any target, no pharmacokinetic parameter in any species, no metabolite quantification beyond identification, no repeat-dose or chronic experiment, no reproductive or developmental study, no carcinogenicity work, and no cognitive or behavioural task beyond the motor and aggression measures the 1984 patent ran. The single human study administered one 20 mg dose to six people for the purpose of establishing detection windows; it recorded no physiological effect, no tolerability data and no laboratory chemistry, and its authors write that the number of subjects is limited and that its concentration and detection-window figures should be treated with caution. ClinicalTrials.gov returns zero registered studies under fladrafinil, CRL-40941, flmodafinil, lauflumide or NLS-4, so no dose-ranging, safety or efficacy trial has been registered there, and no other national or regional registry was searched for this record. What is known about the downstream chemistry is that fladrafinil is a prodrug converted to flmodafinil, and that flmodafinil's own dopamine transporter affinity in rat brain membranes was close to modafinil's in the one head-to-head table located; whether that translates into any difference in a person has not been tested. Fladrafinil holds no marketing authorisation in any jurisdiction. It is named under class S6, stimulants, in the 2026 World Anti-Doping Agency Prohibited List, in force 1 January 2026, in the section listing additional examples of substances the class already prohibited; the naming does not mark the start of its prohibited status. Material sold outside a registered trial has not been subject to identity, purity or content controls, with one of the two products ever assayed in a published paper containing close to double its labelled strength.

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