CNS Drugs 2009;

Although originally developed for the treatment of hypertension, a2agonists have been used to treat Tourette’s syndrome, attention-deficit hyperactivity disorder (ADHD), developmental disorders and substance abuse for nearly three decades. Based on studies of clonidine, a2-agonists were presumed to reduce arousal by decreasing the firing of noradrenaline neurons in locus ceruleus. Accumulated preclinical evidence indicates that guanfacine has features in common with clonidine, in addition to other pharmacological effects. Clonidine binds to the three subtypes of a2-receptors, A, B and C, whereas guanfacine binds more selectively to a2A-receptors, which appears to enhance prefrontal function. Several reports on the use of the a2-agonists show improvements in children with ADHD and improvements in hyperactivity, impulsiveness and inattention in children with tic disorders and pervasive developmental disorders. Both clonidine and guanfacine are associated with sedation, fatigue and somnolence. Reductions in heart rate and blood pressure are modest and rarely lead to discontinuation of treatment across these trials. The a2-agonist clonidine has been used in the treatment of Tourette’s syndrome, attentiondeficit hyperactivity disorder (ADHD), pervasive developmental disorders (PDD) and substance abuse since the late 1970s. Interest in the use of guanfacine, also an a2-agonist, for these conditions has emerged during the past 15 years. Although commonly used in practice, neither clonidine nor guanfacine is approved for these indications by the US FDA. The presumed therapeutic action of a2agonists in ADHD involved turning down the noradrenaline (NA) system in the brain, resulting in decreased arousal. Accumulated evidence during the past 15 years suggests that a2-agonists may also stimulate a2-receptors in the prefrontal cortex (PFC). This action may improve inattention and the control of impulsive behaviour, which are key characteristics in children with ADHD and some children with tic and pervasive developmental disorders. Preclinical data suggest that clonidine and guanfacine may differ in their affinity for a2-receptors in PFC, which may have relevance to clinical outcomes. This article examines the clinical differences between clonidine and guanfacine, the potential implications of these differences, and the evidence supporting the use of clonidine and guanfacine in REVIEW ARTICLE CNS Drugs 2009; 23 Suppl.1: 43-49 1172-7047/09/0001-0043/$49.95/0 a 2009 Adis Data Information BV. All rights reserved.