Modafinil has attracted attention for the treatment of cognitive dysfunction in disorders such as attention-deficit/hyperactivity disorder (ADHD) as well as cocaine and methamphetamine dependence.  However, modafinil has relatively low affinity for binding to the dopamine transporter (DAT) to block dopamine reuptake, and is water-insoluble, thus requiring large doses to achieve pharmacological effects.

Investigators at the National Institute of Drug Abuse have synthesized a series of modafinil analogues that have higher affinity for the dopamine (DAT), serotonin (SERT) and/or norepinephrine (NET) transporters and improved water solubility.  These novel analogues present the advantage of higher potency, which may translate into lower effective doses and better bioavailability over modafinil.

Competitive Advantages:

• Higher affinity for monoamine transporters (DAT, SERT, and NET) compared to modafinil
• Analogues have lower effective doses
• Better bioavailability than modafinil
• Improved water solubility over modafinil

Commercial Applications:

• Therapeutic agent for substance abuse (such as nicotine, cocaine, methamphetamine, opioids), for attention/cognitive disorders (such as ADHD), and for sleep disorders.