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