Flmodafinil
| Chemical Information: | |
|---|---|
| Chemical Name: | 2-[(bis(4-fluorophenyl)methyl)sulfinyl]acetamide |
| CAS Number: | 90280-13-0 |
| Molecular Formula: | C₁₅H₁₃F₂NO₂S |
| Molecular Weight: | 325.33 g/mol |
| Purity: | ≥99% (as confirmed by Liquid Chromatography-Mass Spectrometry, LC-MS) |
Flmodafinil (CRL-40,940): A Comprehensive Guide for Research Applications
Flmodafinil, also known as CRL-40,940, bisfluoromodafinil, and lauflumide, is a synthetic eugeroic compound developed to promote wakefulness and enhance cognitive function. As a bisfluoro analog of modafinil, flmodafinil is reported to have higher potency and bioavailability, leading to increased interest in its research applications.
Development and Purpose
Flmodafinil was developed as part of an effort to create more effective and potent alternatives to modafinil, a well-known wakefulness-promoting agent. By introducing two fluorine atoms into the modafinil structure, researchers aimed to enhance its pharmacokinetic properties, resulting in improved efficacy and reduced side effects.
Key Objectives in Development:
Enhanced Wakefulness Promotion:
Develop a compound with superior efficacy in promoting alertness and reducing excessive daytime sleepiness.
Improved Cognitive Function:
Enhance cognitive performance, including attention, memory, and executive function.
Optimized Pharmacokinetics:
Increase bioavailability and potency compared to modafinil, allowing for lower dosing and potentially fewer side effects.
Mechanisms of Action
While the precise mechanisms of flmodafinil are not fully elucidated, it is believed to function similarly to modafinil with some distinctions:
Dopamine Reuptake Inhibition:
Flmodafinil acts as a weak dopamine reuptake inhibitor, increasing dopamine levels in the brain, which contributes to enhanced wakefulness and mood.
Adrenergic System Modulation:
It may influence adrenergic receptors, promoting alertness and cognitive function.
Glutamatergic and GABAergic Balance:
Flmodafinil is thought to enhance excitatory glutamate transmission while inhibiting inhibitory GABA pathways, supporting cognitive enhancement.
Applications in Research
Flmodafinil’s unique properties make it a subject of interest in various research domains:
Cognitive Enhancement
Studies explore its potential to improve learning, memory, and executive functions, particularly in models of cognitive impairment.
Wakefulness and Sleep Disorders
Research investigates its efficacy in promoting wakefulness and treating conditions like narcolepsy and shift work sleep disorder.
Attention-Deficit Disorders
Flmodafinil is examined for its potential benefits in managing attention-deficit/hyperactivity disorder (ADHD) symptoms.
Mood Disorders
Its effects on mood regulation are studied, considering its influence on dopamine and adrenergic systems.
Mechanism of Action and Pharmacology
According to the Radical Research report, flmodafinil operates primarily as a dopamine reuptake inhibitor. By binding to the dopamine transporter (DAT), it increases extracellular dopamine levels in the brain, a mechanism similar to its parent compound modafinil. This effect is linked to enhanced alertness, improved attention, and potential mood regulation. The study further elaborates that flmodafinil exhibits higher bioavailability and potency compared to modafinil, which may explain its prolonged duration of action. (Radical Research, “Modafinil Pharmacology and Analogues.”)
Applications in Research and Cognitive Enhancement
DBpedia compiled data indicating that flmodafinil’s unique dual-fluoro structure may contribute to its effectiveness as a nootropic. This molecular modification appears to enhance its metabolic stability, prolonging its activity in the body. The data review emphasized its suitability for applications involving attention restoration and cognitive optimization.
“CRL-40,940 has been extensively studied for its implications in cognitive enhancement and mental endurance, presenting a reliable profile for prolonged wakefulness without inducing significant disruptions in circadian rhythms.”(DBpedia Association, “About: CRL-40,940.”)
More studies on the link to Dopamine
The study titled “Dopaminergic role in stimulant-induced wakefulness” by Wisor et al., published in The Journal of Neuroscience in 2001, investigates the role of dopamine in the wake-promoting effects of stimulants. The researchers utilized dopamine transporter knockout mice to assess the impact of dopamine transporter absence on the efficacy of stimulants like modafinil and amphetamine in promoting wakefulness. Their findings indicate that the wakefulness induced by these stimulants is significantly diminished in the absence of dopamine transporters, highlighting the critical role of dopaminergic transmission in mediating the arousal effects of these compounds. This study provides valuable insights into the neurochemical mechanisms underlying stimulant-induced wakefulness.
Fig.1 Effect of modafinil andd-amphetamine on wakefulness and caudate DA efflux in narcoleptic hypocretin receptor 2 mutant dogs. Systemic administration of modafinil (5 mg/kg, i.v.) and d-amphetamine (0.1 mg/kg, i.v.) equipotently increased time spent awake. The most pronounced effect on wakefulness was observed during the first hour after injection [inset; *p < 0.01 for both treatments compared with the respective vehicle treatment (white bars) by Student’s t test;n = 4 per group; mean ± SEM]. Microdialysis experiments demonstrated that administration of amphetamine and modafinil significantly increased extracellular DA levels (p < 0.05;d-amphetamine or modafinil relative to vehicle treatment; repeated-measures ANOVA with Bonferroni’s–Dunn’spost hoc comparisons; n = 4 per group; mean ± SEM). The baseline DA concentrations (at time 0) for modafinil and d-amphetamine sessions were 17.2 ± 3.1 and 17.6 ± 3.5 nm (mean ± SEM), respectively, and did not differ statistically among treatments.VEH, 1 ml of 100% DMSO; d-AMP,d-amphetamine.
Fig. 2. Cumulative effects of GBR12909 (20 mg/kg) and of modafinil (90 mg/kg) on wake in wild-type (+/+) and DAT knock-out (−/−) mice. The cumulative change in wake time (mean ± SEM) in the posttreatment period relative to the corresponding period of the baseline 24 hr pretreatment period is shown for vehicle (open circles) and drug treatment (filled circles). Note large increase in wakefulness in DAT +/+ but not DAT −/− animals. Two-way repeated-measures ANOVA within each genotype indicated significant treatment effect and treatment × time interaction in DAT +/+ but not in DAT −/−. *p < 0.05 drug versus vehicle; Bonferroni’s–Dunn’s post hoc comparisons. Sample sizes (+/+, −/−): vehicle (9, 8); GBR12909, (14, 6); modafinil (10, 9).
Dosage and Administration in Research
In research settings, flmodafinil is typically administered orally. Dosage varies based on study objectives and model specifics:
Low Dose: 5-10 mg/kg for initial assessments of cognitive or wakefulness effects.
Moderate Dose: 20-50 mg/kg for studies focusing on therapeutic potential.
High Dose: 50-100 mg/kg for intensive investigations, with careful monitoring for adverse effects.
Duration of Studies: Research protocols may range from single-dose assessments to chronic administration over several weeks, depending on the study design.
Safety Profile in Research
While flmodafinil shows promise, safety considerations are crucial:
Cardiovascular Effects: Monitor for changes in blood pressure and heart rate, as stimulatory compounds can affect cardiovascular function.
Neurochemical Impact: Assess potential alterations in neurotransmitter levels to evaluate the risk of dependency or neurotoxicity.
Behavioral Changes: Observe for signs of anxiety, agitation, or other behavioral alterations during studies.
Long-Term Effects: Conduct extended studies to identify any chronic effects or potential for tolerance development.
Conclusion
Flmodafinil (CRL-40,940) represents a promising compound for research into wakefulness promotion and cognitive enhancement. Its increased potency and bioavailability compared to modafinil make it an attractive candidate for various studies. However, comprehensive research is necessary to fully understand its mechanisms, efficacy, and safety profile. Researchers should adhere to ethical guidelines and ensure rigorous monitoring throughout their studies.
References
- Radical Research. “Modafinil Pharmacology and Analogues.” https://www.radical-research.com/research/modafinil
- Global MedTech Leader. “The Science Behind Flmodafinil: Exploring its Mechanisms and Cognitive Effects.” https://www.globalmedtechleader.com/the-science-behind-flmodafinil-exploring-its-mechanisms-and-cognitive-effects/
- Wholistic Research. “Flmodafinil (CRL-40,940): Nootropic Benefits, Uses, & Side Effects.” https://wholisticresearch.com/flmodafinil/
- Ijest.org. “Flmodafinil: A Nootropic Powerhouse Or Overpriced Modafinil?” https://www.ijest.org/nootropics/flmodafinil/
- DBpedia Association. “About: CRL-40,940.” https://dbpedia.org/page/CRL-40%2C940
- Dopaminergic role in stimulant-induced wakefulness https://pubmed.ncbi.nlm.nih.gov/11222668/
