Atomoxetine Attenuates Dextroamphetamine Effects in Humans

• Published in: The American journal of drug and alcohol abuse Vol. 35; no. 6; pp. 412 - 416
• Main Authors: Sofuoglu, Mehmet, Poling, James, Hill, Kevin, Kosten, Thomas
• Format: Journal Article
• Language: English
• Published: England Informa UK Ltd 15.12.2009; Taylor & Francis; Taylor & Francis Ltd
• Subjects: Addiction; Adrenergic Uptake Inhibitors - pharmacology; Adult; Affect - drug effects; Amphetamines; Atomoxetine; Atomoxetine Hydrochloride; Blood Pressure; Blood Pressure - drug effects; Central Nervous System Stimulants - antagonists & inhibitors; Central Nervous System Stimulants - pharmacology; Cortisol; dextroamphetamine; Dextroamphetamine - antagonists & inhibitors; Dextroamphetamine - pharmacology; Dextroamphetamines; Drug Abuse; Drug addiction; Drug Interactions; Female; Heart Rate - drug effects; Humans; Hydrocortisone - blood; Male; Methamphetamine; norepinephrine; Norepinephrine Plasma Membrane Transport Proteins - antagonists & inhibitors; Propylamines - pharmacology; Selfreport; Side effects; Stimulants; Studies; Treatment Methods; Volunteers
• DOI: 10.3109/00952990903383961
• ISSN: 0095-2990; 1097-9891

Background: Although preclinical studies support the contribution of the noradrenergic system activation in mediating the acute effects of amphetamines, these findings have not been followed up in clinical studies. Objectives: To examine the effects of atomoxetine, a norepinephrine transporter inhibitor, on subjective, physiological, and plasma cortisol responses to dextroamphetamine in 10 healthy volunteers. Methods: Subjects were randomly assigned to a sequence of atomoxetine (40 mg/day) or placebo treatments each lasting for 4 days. On Day 4 of each treatment period, responses to a single 20 mg/70 kg dose of dextroamphetamine were assessed. Results: Atomoxetine treatment attenuated dextroamphetamine-induced increases in systolic and diastolic blood pressure and plasma cortisol as well as the self-report ratings of "stimulated," "high," and "good drug effects." Conclusions: These findings are consistent with previous preclinical studies supporting the role of the noradrenergic system in mediating acute amphetamine responses. Scientific significance: Atomoxetine's capacity to attenuate some of the physiological and subjective responses to dextroamphetamine supports its potential use for stimulant addiction.