CRL-40,940

CRL-40,940 (Flmodafinil, Lauflumide) is a psychotonic and eugeroic related to Modafinil¹, demonstrating similar but somewhat more potent effects than Modafinil in animal models.

As the bis(p-fluoro) derivative of modafinil, CRL-40,940 (Lauflumide) is sometimes referred to as bisfluoromodafinil or Flmodafinil.

Racemic (±) Modafinil showed K_i at the dopamine transporter (DAT) of 2520nM, while racemic Flmodafinil (CRL-40,940, Lauflumide) had K_i at the dopamine transporter (DAT) of 2190nM².

Adrafinil and the related family of eugeroics including Modafinil, CRL-40,941 and CRL-40,940 were originally invented in the late 1970’s as part of research carried out by the French Laboratoire L. Lafon, led by Dr. Michel Jouvet.

The research team at Lafon observed that “In man, particularly old people, it was observed that … CRL 40940 … administered in the form of gelules or tablets each containing 100 to 200 mg of active ingredient at the rate of 1 to 3 gelules or tablets per day, have given excellent results as arousing medicaments.”¹

More recently, CRL-40,940 has been patented again under the name Lauflumide, as a “novel treatment for ADHD, narcolepsy and idiopathic hypersomnia that would provide better results than those obtained with current treatments based on psychostimulants, would treat symptoms resistant to current treatments with no symptom rebound effect, and would have a low toxicity.”³

In the new patent, the following findings were described: “Surprisingly and unexpectedly, the inventors have synthesized a molecule similar to modafinil and adrafinil and have shown that it is more effective than these two molecules in their indications with fewer side effects. This molecule is lauflumide, or (2-((bis(4-fluorophenyl)methane)sulfinyl)acetamide. Lauflumide is not an amphetamine. Consequently, it does not have the side effects of amphetamines. It [Lauflumide, CRL-40,940, Flmodafinil] is 20 times more effective than adrafinil and 4 times more effective than modafinil. Lauflumide constitutes a therapeutic alternative to methylphenidate and amphetamine in ADHD and to modafinil in narcolepsy and idiopathic hypersomnia. Lauflumide (racemic mixture) has an expected effectiveness in plasma of 6 to 7 hours.”³

The new patent also described the superiority of CRL-40,940 (Flmodafinil, Lauflumide) to Modafinil in the T-maze test. According to the patent, “the test of waiting ability in a T-maze consists in offering a rat a choice between a quick and immediate food reward and a large but delayed reward. In adult Wistar rats, numerous antidepressants such as serotonin or noradrenaline reuptake inhibitors increase the number of choices for the large but delayed reward, indicating an improvement in waiting ability, i.e., a decrease in impulsivity.”³

The patent continues: “Data indicate that the T-maze test with young animals is suitable for testing improvement in impulsivity control by drugs for the treatment of ADHD. An improvement in Waiting ability by this compound would indicate that this compound reduces impulsivity and, consequently, could be useful in the treatment of ADHD. Methylphenidate and d-amphetamine are used as a reference product in the same experiment. … Mazindol, lauflumide in its racemic mixture form or its D form ((+) enantiomer), administered in 3 doses before the test, improve waiting ability in young Wistar rats subjected to the T-maze test compared to the control. Mazindol and D-lauflumide are at least as effective as methylphenidate and d-amphetamine in improving waiting ability in young Wistar rats subjected to the T-maze test. Mazindol and D-lauflumide are more effective than modafinil in improving waiting ability in young Wistar rats subjected to the T-maze test.”³

CRL-40,940 (Flmodafinil, Lauflumide) is predicted to be the main active metabolite of CRL-40,941 (Fladrafinil). Compared to Modafinil, and Adrafinil, this parent Adrafinil-like compound corresponding to Flmodafinil (CRL-40,940, Lauflumide) was observed by its inventors at Laboratoires Lafon to have similar psychotonic and eugeroic properties, but to have unique advantages: namely antiaggressive properties and improved bioavailability by the oral route, and demonstrating more potent effects than Adrafinil in animal models^4,5.