Targeting Catecholamines to Develop New Drugs for Attention Deficit Hyperactivity Disorder

Abstract

The prevalence of attention deficit hyperactivity disorder (ADHD), a developmental neuropsychiatric disorder, is high among children and adolescents. The pathogenesis of ADHD is mediated with genetic, biological, and environmental factors. Most therapeutic drugs for ADHD have so far targeted biological causes, primarily by regulating catecholaminergic neurotransmitters. However, ADHD drugs that are clinically treated have various problems in their addictiveness and drug stability; thus, it is recommended that efficacy and safety should be secured through simultaneous prescription of multiple drugs rather than a single drug treatment. Accordingly, it is necessary to develop drugs that newly target pathogenic mechanisms of ADHD. In this study, we attempt to confirm the possibility of developing new drugs by reviewing dopamine-related developmental mechanisms of neurons and their correlation with ADHD. Histone deacetylase inhibitors (HDACi) can regulate the concentration of intracellular dopamine in neurons by expressing vesicular monoamine transporter 2 and inducing the exocytosis of neurotransmitters to the synaptic cleft, thereby promoting the development of neurons and signal transmission. This cellular modulation of HDACi is expected to treat ADHD by regulating endogenous catecholamines such as dopamine. Although studies are still in the preclinical stage, HDAC inhibitors clearly have potential as a therapeutic agent with low addictiveness and high efficacy for ADHD treatment.