title: Evaluation of the abuse liability of modafinil and other drugs for excessive daytime sleepiness associated with narcolepsy.
abstract: Psychostimulants have been used routinely for the treatment of the disabling daytime sleepiness associated with narcolepsy. However, the perceived and real potential for abuse of amphetamine and amphetaminelike stimulants prompted a search for new wake-promoting compounds with lower dependency and abuse liabilities. Modafinil is a novel wake-promoting agent with a mechanism of action that differs markedly from that of amphetamine and amphetamine-like stimulants. In controlled clinical trials, modafinil has been shown to be an effective and well-tolerated treatment for excessive daytime sleepiness (EDS) in patients with narcolepsy. With a benzhydrylsulfinylacetamide structure, modafinil has a low level of solubility in water (< 1 mg/mL) and is unstable at temperatures > or = 180 degrees C, physicochemical properties that reduce the potential for its abuse via intravenous injection and smoking, respectively. Available preclinical and clinical data on the abuse liability of modafinil suggest a much lower potential for abuse and dependency than amphetaminelike stimulants commonly used for treating EDS in patients with narcolepsy. Therefore, modafinil represents a valuable therapeutic option for the treatment of EDS associated with narcolepsy.
authors.affiliation: Center for Chemical Dependence, Johns Hopkins Bayview Medical Center, Baltimore, Maryland, USA.
authors.forename: D R
authors.initials: DR
authors.lastname: Jasinski
authors.forename: R
authors.initials: R
authors.lastname: Kovacević-Ristanović
mesh_terms: D001559:Benzhydryl Compounds / Q000009:adverse effects* / Q000737:chemistry / Q000627:therapeutic use; D000697:Central Nervous System Stimulants / Q000009:adverse effects* / Q000737:chemistry / Q000627:therapeutic use; D006801:Humans; D000077408:Modafinil; D009290:Narcolepsy / Q000188:drug therapy*; D019966:Substance-Related Disorders / Q000523:psychology*
chemical_list: D001559:Benzhydryl Compounds; D000697:Central Nervous System Stimulants; D000077408:Modafinil