Analogues of Modafinil for treating sleep and attention disorders

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.