Chapter 11 - Molecular Pharmacology and the Treatment of Tourette's Syndrome and Attention Deficit-Hyperactivity Disorder

Abstract

It is noted that α2-adrenoceptor agonist, guanfacine, is currently in use for the treatment of attention deficit-hyperactivity disorder (ADHD) and for Tourette's syndrome. Tourette's patients activate the prefrontal cortex (PFC) when they successfully inhibit their tics. The use of guanfacine to treat these disorders arose from research in animals, elucidating the critical neuromodulatory effects of catecholamines on PFC function. Furthermore, studies in genetically-modified mice have identified the α2A-adrenoceptor as the molecular target for guanfacine's therapeutic actions. Studies in monkeys have shown that stimulation of this receptor at its postsynaptic sites in PFC strengthens PFC regulation of behavior at the cellular and behavioral levels. Future strategies for the treatment of neuropsychiatric illness can be sufficiently informed by basic neuroscience to permit a wholly rational approach. This includes sound understanding of the brain circuits underlying distinct neuropsychiatric symptoms, knowledge of the neurochemical needs of those circuits, and the ability to optimize the neurochemical environment for that circuit with the appropriate medication.