Modafinil, the parent drug, is a wake-promoting prescription medication that is approved by the Food and Drug Administration for the treatment of narcolepsy and other sleep disorders. Currently, modafinil is being investigated as a treatment for psychostimulant (cocaine and methamphetamine) addiction. Like cocaine and methamphetamine, modafinil’s primary biological target is the dopamine transporter (DAT); however, it binds the DAT differently than cocaine and shows no evidence of abuse liability in humans (Loland et al, 2012; Mereu et al, 2013). Early clinical trials reported that modafinil successfully reduced cocaine intake and prevented relapse more effectively than placebo treatments (Dackis et al, 2005; Hart et al, 2008). Yet, larger and more recent multi-center trials have reported only modest advantages of modafinil over placebo in promoting cocaine abstinence (Anderson et al, 2009; Dackis et al, 2012). It is clear that modafinil - which is water-insoluble, displays relatively low inherent binding affinity for the DAT, and must therefore be administered in large doses (up to 400 mg/day) in order to achieve its therapeutic effects - leaves much to be desired as a stand-alone pharmacotherapy to treat psychostimulant addictions.The modafinil analogues synthesized at NIDA offer significant pharmacokinetic improvements over the parent drug while retaining its atypical (non-addictive) DAT binding profile (Okunola-Bakare et al, 2014). Furthermore, these new compounds display significantly higher binding affinity for the DAT (up to 20-fold) with enhanced selectivity for the DAT over other monoamine transporters (up to 2,900-fold increases in SERT:DAT and NET:DAT affinity ratios) compared to modafinil. Lastly, salts of these newly-synthesized amine compounds present a significant solubility advantage over the non-aminergic and water-insoluble parent drug. Altogether, these more potent analogs offer greater bioavailability and lower effective doses for the avoidance of side effects.
Our company's first technology is an in-licensed chemical library of potent and selective modafinil analogues developed by investigators Amy Newman, Jianjing Cao, and Oluyomi Okunola-Bakare at the National Institute on Drug Abuse (NIDA) (Intellectual Property: US Application No. 61/774,878). These compounds offer a wide range of competitive pharmacokinetic advantages over the parent drug modafinil and other drugs currently being evaluated as treatments for psychostimulant use disorders. EncepHeal is interested in and is capable of collaborative research with NIDA to further evaluate and commercialize a select number (1-3) of these compounds as potential therapeutic agents for the treatment of psychostimulant abuse and addiction.
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