Flmodafinil

Overview

• Flmodafinil:
  • Also known as bisfluoromodafinil and lauflumide.
  • Related to modafinil, developed for various medical conditions.
  • Uses: Chronic fatigue syndrome, idiopathic hypersomnia, narcolepsy, ADHD, and Alzheimer's disease.
  • Non-medical use: Sold online as a nootropic (cognitive enhancer).

Pharmacology

Pharmacodynamics

• Action: Selective atypical dopamine reuptake inhibitor (DRI).
  • Inhibits dopamine transporter (DAT) effectively (Ki = 4,090 nM).
  • Lower affinity for serotonin transporter (SERT) and negligible for σ1 receptor.
• Effects:
  • Increases dopamine in nucleus accumbens (150-200% of baseline).
  • Greater wakefulness promotion compared to modafinil with less sleep architecture disruption.
  • Does not induce cytochrome P450 enzymes (e.g., CYP3A4/5).

Comparison to Modafinil:

• Advantages:
  • Longer-lasting wake-promoting effects.
  • Minimal sleep rebound and reduced slow-wave EEG disruption.
• Mechanism:
  • Blocks DAT by 83% (higher than methylphenidate) with no adrenergic side effects.

Chemistry

• Structure: Racemic mixture of (S)-(+)- and (R)-(–)-enantiomers.
  • Enantiomers named JBG1-048 (S) and JBG1-049 (R).
• Related analogues: Modafinil, armodafinil, fladrafinil, and others.

History

• Patented in the 1980s; further developed in 2013.
• Preclinical research started in 2015.
• Current focus: Chronic fatigue syndrome.
  • Discontinued for narcolepsy, ADHD, and Alzheimer's.

Research

• Ongoing studies on its pharmacokinetics and wake-promoting mechanisms.
• Early data suggests high efficacy and minimal side effects in animals.

Key Notes

• Advantages over modafinil:
  • Does not induce liver enzymes.
  • Longer wakefulness effects with less sleep disruption.
• Current Status: In preclinical development for chronic fatigue syndrome.