CRL-40,941

Last updated
CRL-40,941
CRL-40,941.svg
Clinical data
Other namesCRL-40,941; Fluorafinil; Bisfluoroadrafinil
Routes of
administration
By mouth
ATC code
  • None
Legal status
Legal status
  • US:Not approved
Identifiers
  • 2-{[Bis(4-fluorophenyl)methyl]sulfinyl}-N-hydroxyacetamide
CAS Number
PubChem CID
ChemSpider
UNII
CompTox Dashboard (EPA)
Chemical and physical data
Formula C15H13F2NO3S
Molar mass 325.33 g·mol−1
3D model (JSmol)
  • C1=CC(=CC=C1C(C2=CC=C(C=C2)F)S(=O)CC(=O)NO)F
  • InChI=1S/C15H13F2NO3S/c16-12-5-1-10(2-6-12)15(22(21)9-14(19)18-20)11-3-7-13(17)8-4-11/h1-8,15,20H,9H2,(H,18,19) X mark.svgN
  • Key:VKGUUSVYPXTWMA-UHFFFAOYSA-N X mark.svgN
 X mark.svgNYes check.svgY  (what is this?)    (verify)

Fladrafinil (developmental code name CRL-40,941), also known as fluorafinil or as bisfluoroadrafinil, is a wakefulness-promoting agent related to modafinil that was never marketed. [1] [2] [3] It is sold online and used non-medically as a nootropic (cognitive enhancer). [1] [2] [3]

Contents

Modafinil and its analogues are known to act as dopamine reuptake inhibitors and this is thought to be involved in their wakefulness-promoting effects. [1] Chemically, fladrafinil is a derivative of adrafinil (N-hydroxymodafinil) and is also known as bisfluoroadrafinil (it is the bis(4-fluoro) phenyl ring-substituted derivative of adrafinil). [1] It is closely related to flmodafinil (CRL-40,940; bisfluoromodafinil). [1] [2] [3]

Pharmacology

Fladrafinil has been found to produce antiaggressive effects in animals, which adrafinil does not produce. [4] [ failed verification ] Fladrafinil is purportedly 3 to 4 times more potent than adrafinil in this action. [4]

Chemistry

Analogues of fladrafinil include modafinil, armodafinil ((R)-modafinil), esmodafinil ((S)-modafinil), adrafinil (CRL-40,028; N-hydroxymodafinil), flmodafinil (CRL-40,940; bisfluoromodafinil), and CE-123, among others. [2]

History

Fladrafinil appears to have first been patented in the 1980s. [5]

Research

The pharmacokinetics of fladrafinil are being studied. [6]

Related Research Articles

<span class="mw-page-title-main">Modafinil</span> Eugeroic medication

Modafinil, sold under the brand name Provigil among others, is a wakefulness-promoting medication used primarily to treat narcolepsy, a sleep disorder characterized by excessive daytime sleepiness and sudden sleep attacks. Modafinil is also approved for stimulating wakefulness in people with sleep apnea and shift work sleep disorder. It is taken by mouth. Modafinil is not approved by the US Food and Drug Administration (FDA) for use in people under 17 years old.

<span class="mw-page-title-main">Nootropic</span> Compound intended to improve cognitive function

Nootropics, colloquially brain supplements, smart drugs and cognitive enhancers, are natural, semisynthetic or synthetic compounds which purportedly improve cognitive functions, such as executive functions, attention or memory.

A dopamine reuptake inhibitor (DRI) is a class of drug which acts as a reuptake inhibitor of the monoamine neurotransmitter dopamine by blocking the action of the dopamine transporter (DAT). Reuptake inhibition is achieved when extracellular dopamine not absorbed by the postsynaptic neuron is blocked from re-entering the presynaptic neuron. This results in increased extracellular concentrations of dopamine and increase in dopaminergic neurotransmission.

<span class="mw-page-title-main">Aniracetam</span> Medication

Aniracetam, also known as N-anisoyl-2-pyrrolidinone, is a racetam which is sold in Europe as a prescription drug. It is not approved by the Food and Drug Administration for use in the United States as a prescription medication or dietary supplement. Despite the FDA's lack of approval, the drug is readily available over-the-counter in misbranded dietary supplements.

<span class="mw-page-title-main">Adrafinil</span> Wakefulness-promoting drug

Adrafinil, sold under the brand name Olmifon, is a wakefulness-promoting medication that was formerly used in France to improve alertness, attention, wakefulness, and mood, particularly in the elderly. It was also used off-label by individuals who wished to avoid fatigue, such as night workers or others who needed to stay awake and alert for long periods of time. Additionally, the medication has been used non-medically as a novel vigilance-promoting agent.

<span class="mw-page-title-main">Armodafinil</span> Eugeroic medication

Armodafinil (trade name Nuvigil) is the enantiopure compound of the eugeroic modafinil (Provigil). It consists of only the (R)-(−)-enantiomer of the racemic modafinil. Armodafinil is produced by the pharmaceutical company Cephalon Inc. and was approved by the U.S. Food and Drug Administration (FDA) in June 2007. In 2016, the FDA granted Mylan rights for the first generic version of Cephalon's Nuvigil to be marketed in the U.S.

<span class="mw-page-title-main">(+)-CPCA</span> Stimulant drug

(+)-CPCA is a stimulant drug similar in structure to pethidine and to RTI-31, but nocaine lacks the two-carbon bridge of RTI-31's tropane skeleton. This compound was first developed as a substitute agent for cocaine.

<span class="mw-page-title-main">IDRA-21</span> Chemical compound

IDRA-21 is a positive allosteric modulator of the AMPA receptor and a benzothiadiazine derivative. It is a chiral molecule, with (+)-IDRA-21 being the active form.

<span class="mw-page-title-main">Fluorenol</span> Chemical compound

Fluorenol, also known as hydrafinil, is an alcohol derivative of fluorene. In the most significant isomer, fluoren-9-ol or 9-hydroxyfluorene, the hydroxy group is located on the bridging carbon between the two benzene rings. Hydroxyfluorene can be converted to fluorenone by oxidation. It is a white-cream colored solid at room temperature.

<i>N</i>-Phenylacetyl-<small>L</small>-prolylglycine ethyl ester Prodrug

N-Phenylacetyl-l-prolylglycine ethyl ester is promoted as a nootropic and is a prodrug of cyclic glycine-proline. Other names include the brand name Noopept, developmental code GVS-111, and proposed INN omberacetam.

<span class="mw-page-title-main">Eugeroic</span> Drug for wakefulness and alertness

Eugeroics, also known as wakefulness-promoting agents and wakefulness-promoting drugs, are a class of drugs that promote wakefulness and alertness. They are medically indicated for the treatment of certain sleep disorders including excessive daytime sleepiness (EDS) in narcolepsy or obstructive sleep apnea (OSA). Eugeroics are also often prescribed off-label for the treatment of EDS in idiopathic hypersomnia. In contrast to classical psychostimulants, such as methylphenidate and amphetamine, which are also used in the treatment of these disorders, eugeroics typically do not produce marked euphoria, and, consequently, have a lower addictive potential.

<span class="mw-page-title-main">Sunifiram</span> Chemical compound

Sunifiram is an experimental drug which has antiamnesic effects in animal studies and with significantly higher potency than piracetam. Sunifiram is a molecular simplification of unifiram (DM-232). Another analogue is sapunifiram (MN-19). As of 2016, sunifiram had not been subjected to toxicology testing, nor to any human clinical trials, and is not approved for use anywhere in the world.

Neuroenhancement or cognitive enhancement is the experimental use of pharmacological or non-pharmacological methods intended to improve cognitive and affective abilities in healthy people who do not have a mental illness. Agents or methods of neuroenhancement are intended to affect cognitive, social, psychological, mood, or motor benefits beyond normal functioning.

<span class="mw-page-title-main">5-Chloro-αMT</span> Chemical compound

5-Chloro-α-methyltryptamine (5-Chloro-αMT), also known as PAL-542, is a tryptamine derivative related to α-methyltryptamine (αMT) and one of only a few known specific serotonin-dopamine releasing agents (SDRAs). It has been investigated in animals as a potential treatment for cocaine dependence. The EC50 values of 5-chloro-αMT in evoking the in vitro release of serotonin (5-HT), dopamine (DA), and norepinephrine (NE) in rat synaptosomes were reported as 16 nM, 54 nM, and 3434 nM, with an NE/DA ratio of 63.6 and a DA/5-HT ratio of 3.38, indicating that it is a highly specific and well-balanced SDRA. However, 5-chloro-αMT has also been found to act as a potent full agonist of the 5-HT2A receptor, with an EC50 value of 6.27 nM and an efficacy of 105%. It is likely to act as a potent agonist of other serotonin receptors as well.

<span class="mw-page-title-main">Modafinil acid</span> Chemical compound

Modafinil acid (code name CRL-40467), also known as modafinilic acid or modafinil carboxylate, is one of the two major metabolites of modafinil – the other being modafinil sulfone. Modafinil acid is also a metabolite of the modafinil prodrug, adrafinil, and the (R)-(–)-enantiomer is a metabolite of armodafinil, the (R)-(–)-enantiomer of modafinil. Between 30 - 60% of modafinil is converted to modafinil acid and its half life is roughly half that of modafinil (about 7 hours). Modafinil acid seems to be inactive, and similarly to modafinil sulfone, does not appear to contribute to the wakefulness-promoting/psychostimulant effects of modafinil.

<span class="mw-page-title-main">CRL-40,940</span> Wakefulness-promoting drug/Dopamine reuptake inhibitor

Flmodafinil, also known as bisfluoromodafinil and lauflumide, is a wakefulness-promoting agent related to modafinil which has been developed for treatment of a variety of different medical conditions. These include chronic fatigue syndrome, idiopathic hypersomnia, narcolepsy, attention deficit hyperactivity disorder (ADHD), and Alzheimer's disease. Aside its development as a potential pharmaceutical drug, flmodafinil is sold online and used non-medically as a nootropic.

<span class="mw-page-title-main">Modafinil sulfone</span> Chemical compound

Modafinil sulfone (code name CRL-41056) is an achiral, oxidized metabolite of modafinil, a wakefulness-promoting agent. It is one of two major circulating metabolites of modafinil, the other being modafinil acid. Modafinil sulfone is also a metabolite of the modafinil prodrug, adrafinil. Modafinil sulfone is also a metabolite of armodafinil, the (R)-(–)-enantiomer of modafinil, as oxidation to the sulfone removes the chiral center at the sulfur atom. Modafinil sulfone has been described as inactive, and similarly to modafinil acid, does not appear to contribute to the wakefulness-promoting effects of modafinil. However, like modafinil, modafinil sulfone was found to show anticonvulsant properties in animals, indicating that it does possess some biological activity.

<span class="mw-page-title-main">CE-123</span> Designer drug, analog of modafinil

CE-123 is an analog of modafinil, the most researched of a series of structurally related heterocyclic derivatives. In animal studies, CE-123 was found to improve performance on tests of learning and memory in a manner consistent with a nootropic effect profile.

References

  1. 1 2 3 4 5 Sousa A, Dinis-Oliveira RJ (2020). "Pharmacokinetic and pharmacodynamic of the cognitive enhancer modafinil: Relevant clinical and forensic aspects". Subst Abus. 41 (2): 155–173. doi:10.1080/08897077.2019.1700584. PMID   31951804. Modafinil is a highly researched compound, with many analogues created and studied (Figure 1); the wakefulness promoting agents CRL-40,490 and modafiendz are the fluoro and N-methyl analogs of modafinil and the CRL-40,491 is the fluoro analog of adrafinil.30,31 [...] Although the long-term effects in healthy individuals are unknown, modafinil is easily available online with limited information about the use of and potential harms related to the drug.20,209 Other possibilities available from online shops and other retail outlets include adrafinil, CRL-40,940, CRL40,941 and modafiendz.30 Alternatively to online purchase, students also report to obtain stimulants from a pharmacy with or without prescription, from colleagues, friends or family, or from an herbalist.20
  2. 1 2 3 4 Schifano F, Catalani V, Sharif S, Napoletano F, Corkery JM, Arillotta D, Fergus S, Vento A, Guirguis A (April 2022). "Benefits and Harms of 'Smart Drugs' (Nootropics) in Healthy Individuals". Drugs. 82 (6): 633–647. doi:10.1007/s40265-022-01701-7. PMID   35366192. [Modafinil] is widely available for online purchase [105] and it is of interest that a range of modafinil derivatives are actively being discussed on web fora, including: adrafinil, fladrafinil, flmodafinil, and N-methyl-4,4′-difluoro-modafinil [8]. Finally, the modafinil R-enantiomer armodafinil, which is being used to improve wakefulness in patients with excessive sleepiness [106], is currently the subject of an anecdotal debate relating to its properties as a [cognitive enhancer] [107].
  3. 1 2 3 Dowling G, Kavanagh PV, Talbot B, O'Brien J, Hessman G, McLaughlin G, Twamley B, Brandt SD (March 2017). "Outsmarted by nootropics? An investigation into the thermal degradation of modafinil, modafinic acid, adrafinil, CRL-40,940 and CRL-40,941 in the GC injector: formation of 1,1,2,2-tetraphenylethane and its tetra fluoro analog". Drug Test Anal. 9 (3): 518–528. doi:10.1002/dta.2142. PMID   27928893.
  4. 1 2 US 4489095,Lafon L,"Halogenobenzhydrylsulfinylacetohydroxamic acids",published 1984-12-18, assigned to Laboratoire L. Lafon
  5. "Fladrafinil". PubChem. Retrieved 18 August 2024.
  6. "Investigations into the metabolism and elimination of flmodafinil and fladrafinil as well as their prevalence in elite sports". World Anti Doping Agency. 23 May 2024. Retrieved 18 August 2024.