title: Discriminative-stimulus, self-reported, performance, and cardiovascular effects of atomoxetine in methylphenidate-trained humans.
abstract: Atomoxetine is marketed as a nonstimulant medication indicated for the treatment of attention-deficit/hyperactivity disorder in adults. Previous laboratory research suggests that atomoxetine has limited abuse potential but that some of its behavioral effects might overlap with traditional psychomotor stimulants like methylphenidate and d-amphetamine. A drug with this profile might be useful for the treatment of stimulant dependence. The aim of this experiment was to compare the discriminative-stimulus and self-reported effects of atomoxetine with methylphenidate, damphetamine, and triazolam in humans who had acquired a methylphenidate (30 mg) discrimination. Six healthy subjects with a recent history of nontherapeutic stimulant use were enrolled in this outpatient study. After subjects acquired the methylphenidate discrimination, a range of doses of methylphenidate (5-30 mg), atomoxetine (15-90 mg), d-amphetamine (2.5-15 mg), triazolam (0.06-0.375 mg), and placebo were tested. To more fully characterize the behavioral effects of atomoxetine, a battery of self-reported drug-effect questionnaires, a performance task, and cardiovascular assessments were also included. Methylphenidate and d-amphetamine increased drug-appropriate responding and produced typical stimulant-like effects (e.g., increased ratings of "Active, Alert, Energetic"). Atomoxetine partially substituted for methylphenidate (i.e., 33%-50%) and produced some dose-dependent, stimulant-like, subject-rated drug effects, although the magnitude of these effects was less than d-amphetamine and methylphenidate and generally did not attain statistical significance. These data suggest that the behavioral effects of atomoxetine overlap to a small degree with psychomotor stimulants and that it has low abuse potential.
authors.affiliation: Department of Behavioral Science, University of Kentucky College of Medicine, Lexington, 40536-0086, USA.
authors.forename: Joshua A
authors.initials: JA
authors.lastname: Lile
authors.forename: William W
authors.initials: WW
authors.lastname: Stoops
authors.forename: Todd M
authors.initials: TM
authors.lastname: Durell
authors.forename: Paul E A
authors.initials: PE
authors.lastname: Glaser
authors.forename: Craig R
authors.initials: CR
authors.lastname: Rush
mesh_terms: D000293:Adolescent; D000328:Adult; D000069445:Atomoxetine Hydrochloride; D001794:Blood Pressure / Q000187:drug effects*; D004193:Discrimination Learning / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006339:Heart Rate / Q000187:drug effects*; D006801:Humans; D008297:Male; D008774:Methylphenidate / Q000494:pharmacology*; D050484:Norepinephrine Plasma Membrane Transport Proteins / Q000502:physiology; D011437:Propylamines / Q000494:pharmacology*
chemical_list: D050484:Norepinephrine Plasma Membrane Transport Proteins; D011437:Propylamines; D008774:Methylphenidate; D000069445:Atomoxetine Hydrochloride